Background: Masked hypertension is more common in individuals with type 2 diabetes than in individuals with normoglycemia. We aimed to explore if there is a discrepancy between office blood pressure (office BP) and home blood pressure monitoring (HBPM) in relation to HbA1c as well as glycemic status in 5,029 middle-aged individuals.

Methods: HBPM was measured in a subsample of 5,029 participants in The Swedish CardioPulmonary BioImage Study (SCAPIS), a population-based cohort of 50–64 years old participants. Both office BP and HBPM were obtained after 5 minutes’ rest using the semiautomatic Omron M10-IT oscillometric device. White coat effect was calculated by subtracting systolic HBPM from systolic office BP. Participants were classified according to glycemic status: Normoglycemia, prediabetes, or diabetes based on fasting glucose, HbA1c value, and self-reported diabetes diagnosis.

Results: Of the included 5,025 participants, 947 (18.8%) had sustained hypertension, 907 (18.0%) reported taking antihypertensive treatment, and 370 (7.4%) had diabetes mellitus. Both systolic office BP and HBPM increased according to worsened glycemic status (P for trend 0.002 and 0.002, respectively). Masked hypertension was more prevalent in participants with dysglycemia compared with normoglycemia (P = 0.036). The systolic white coat effect was reversely associated with HbA1c (P = 0.012).

Conclusions: The systolic white coat effect was reversely associated with HbA1c, and the prevalence of masked hypertension increased with dysglycemia.

Background: Masked hypertension is associated with cardiovascular disease (CVD). However, previous large studies have not used the same device to measure office and home blood pressure (BP) and adhered to current home BP measurement recommendations of the European Society of Hypertension. We aimed to characterize masked hypertension and explore its relation to manifestations of CVD.

Methods: A randomly selected cohort of 5057 participants aged 50–64 years from the Swedish CardioPulmonary BioImage Study (SCAPIS) was evaluated with office and home BP using the semi-automatic Omron M10-IT oscillometric device. Additional analyses included pulse wave velocity (PWV) and coronary artery calcium score (CACS).

Results: Of participants, 4122 did not have current antihypertensive treatment, and were thus included in our analyses. Of these, 2634 (63.9%) had sustained normotension, and 172 (4.2%) had masked hypertension. Participants with masked hypertension vs. sustained normotension were more often men (66.9 vs. 46.2%, P < 0.001). Those with masked hypertension had higher mean PWV [9.3 (95% confidence interval, 95% CI 9.1–9.5) vs. 8.3 (95% CI 8.2–8.4) m/s, P < 0.001] and odds ratio for CACS at least 100 [1.65 (95% CI 1.02–2.68), P = 0.040]. These associations were similar in a posthoc analysis of masked hypertension and sustained normotension, matched for age, sex and systolic office BP.

Conclusion: Masked hypertension was associated with markers of CVD. This suggests that home BP is a better predictor of risk, even when the recordings are performed with the same measurement device, in a population-based setting with randomized recruitment.

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Objective. To explore the association between abdominal obesity and insulin resistance in patients with type 2 diabetes. Design. A cross-sectional observational study. Setting. Primary care in Skara, Sweden. Subjects. A total of 198 men and 186 women with type 2 diabetes who consecutively completed an annual check-up in 1992-1993. Main outcome measures. Abdominal obesity was defined according to criteria for the metabolic syndrome using the waist circumference (WC): > 102 cm for men and > 88 cm for women. Insulin resistance was estimated using the Homeostasis Model Assessment (HOMA), and was dichotomized by the 75th percentile (IR). Results. Abdominal obesity was found in 66 men (33%), and in 106 women (57%). Pearson's correlation coefficients between components of the metabolic syndrome and IR were statistically significant for WC, waist-hip ratio, serum triglycerides, and HDL cholesterol, and were higher for WC (0.40) than for waist-hip ratio (0.23) in both genders (p < 0.001). The association between WC and IR was challenged by successively entering other components of the metabolic syndrome into the model in a logistic regression. In the final model, adjusting for differences in age, systolic blood pressure, HbA1c, serum triglycerides, HDL cholesterol, and microalbuminuria, the association remained statistically significant both in men (OR 8.6, 95% CI 3.0-25.2, p < 0.001), and in women (OR 5.6, 95% CI 1.7-18.1, p = 0.004). Conclusions. WC provides a feasible measure for insulin resistance in the vast majority of subjects with type 2 diabetes. It is convenient and less expensive than direct means and could be used as a proxy for insulin resistance in population studies.

Objective Blood pressure variability (BPV) has been associated with risk of cardiovascular events in observational studies, independently of mean BP levels. In states with higher autonomic imbalance, such as in diabetes, the importance of BP variability may theoretically be even greater. We aimed to investigate the incremental value of BPV for prediction of cardiovascular and all-cause mortality in patients with type 2 diabetes. Methods We identified 9,855 patients without pre-existing cardiovascular disease who did not change BP-lowering treatment during the observation period from a Swedish primary health care cohort of patients with type 2 diabetes. BPV was summarized as the standard deviation (SD), coefficient of variation (CV), or variation independent of mean (VIM). Patients were followed for a median of 4 years and associations with cardiovascular and all-cause mortality were investigated using Cox proportional hazards models. Results BPV was not associated with cardiovascular specific or all-cause mortality in the total sample. In patients who were not on BP-lowering drugs during the observation period (n = 2,949), variability measures were associated with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50% increases in SD, CV and VIM, respectively, adjusted for Framingham risk score risk factors, including mean BP. However, the addition of the variability measures in this subgroup only led to very minimal improvement in discrimination, indicating they may have limited clinical usefulness (change in C-statistic ranged from 0.000-0.003 in all models). Conclusions Although BPV was independently associated with all-cause mortality in diabetes patients in primary care who did not have pre-existing cardiovascular disease or BP-lowering drugs, it may be of minimal clinical usefulness above and beyond that of other routinely measured predictors, including mean BP.

Aims/hypothesis Non-Western immigrants to Europe are at high risk for type 2 diabetes. In this nationwide study including incident cases of type 2 diabetes, the aim was to compare all-cause mortality (ACM) and cause-specific mortality (CSM) rates in first- and second-generation immigrants with native Swedes. Methods People living in Sweden diagnosed with new-onset pharmacologically treated type 2 diabetes between 2006 and 2012 were identified through the Swedish Prescribed Drug Register. They were followed until 31 December 2016 for ACM and until 31 December 2012 for CSM. Analyses were adjusted for age at diagnosis, sex, socioeconomic status, education, treatment and region. Associations were assessed using Cox regression analysis. Results In total, 138,085 individuals were diagnosed with type 2 diabetes between 2006 and 2012 and fulfilled inclusion criteria. Of these, 102,163 (74.0%) were native Swedes, 28,819 (20.9%) were first-generation immigrants and 7103 (5.1%) were second-generation immigrants with either one or both parents born outside Sweden. First-generation immigrants had lower ACM rate (HR 0.80 [95% CI 0.76, 0.84]) compared with native Swedes. The mortality rates were particularly low in people born in non-Western regions (0.46 [0.42, 0.50]; the Middle East, 0.41 [0.36, 0.47]; Asia, 0.53 [0.43, 0.66]; Africa, 0.47 [0.38, 0.59]; and Latin America, 0.53 [0.42, 0.68]). ACM rates decreased with older age at migration and shorter stay in Sweden. Compared with native Swedes, first-generation immigrants with &lt;= 24 years in Sweden (0.55 [0.51, 0.60]) displayed lower ACM rates than those spending &gt;24 years in Sweden (0.92 [0.87, 0.97]). Second-generation immigrants did not have better survival rates than native Swedes but rather displayed higher ACM rates for people with both parents born abroad (1.28 [1.05, 1.56]). Conclusions/interpretation In people with type 2 diabetes, the lower mortality rate in first-generation non-Western immigrants compared with native Swedes was reduced over time and was equalised in second-generation immigrants. These findings suggest that acculturation to Western culture may impact ACM and CSM in immigrants with type 2 diabetes but further investigation is needed.

Aims The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden. Methods and results The study enrolled 3809 individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 &gt; 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76-8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS &gt; 0 and in those with both carotid plaques and CACS &gt; 0, compared with individuals without subclinical atherosclerotic burdens (87.5 +/- 5.6% and 86.9 +/- 6.0%, vs. 88.6 +/- 5.8%, P &lt; 0.01). Conclusion In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments.

Background: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. Methods and Results: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score &gt;= 4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P&lt;0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score &gt;= 4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score &gt;= 100 performed similarly. Conclusions: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or &gt;= 50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (&gt;= 50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score &gt;400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

Background and aims: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.Methods: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomog-raphy angiography (CCTA) and expressed as segment involvement score (SIS).Results: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Conclusions: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

ObjectiveTo evaluate microvascular function in women with previous hypertensive disorders of pregnancy (HDP).DesignRetrospective population-based cohort study.SettingLinkoping, Sweden.PopulationWomen aged 50-65 years, participating in the Swedish CArdioPulmonary bioImage Study (SCAPIS) at one site (Linkoping) 2016-18, who underwent microcirculatory assessment (N = 1222).MethodsForearm skin comprehensive microcirculatory assessment was performed with a PeriFlux PF6000 EPOS (Enhanced Perfusion and Oxygen Saturation) system measuring oxygen saturation and total speed resolved perfusion. Obstetric records were reviewed to identify women with previous HDP. Data on cardiovascular risk factors, comorbidities, medication, lifestyle, anthropometric data, and biochemical analyses were obtained from SCAPIS. The microcirculatory data were compared between women with and without previous HDP.Main outcome measuresSkin microcirculatory oxygen saturation and total speed resolved perfusion at baseline and post-ischaemic peak.ResultsWomen with previous pre-eclampsia displayed impaired post-ischaemic peak oxygen saturation compared with women with normotensive pregnancies (88%, interquartile range [IQR] 84-89% vs 91%, IQR 87-94%, p = 0.001) 6-30 years after pregnancy. The difference remained after multivariable adjustment (& beta; -2.69, 95% CI -4.93 to -0.45).ConclusionsThe findings reveal microvascular dysfunction at long-term follow up in women with previous pre-eclampsia and strengthen the possible role of endothelial dysfunction as a link to the increased risk of cardiovascular disease in women with HDP.

Rationale: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity of the lung for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure. Objective: To study the prevalence of CAL, emphysema, and impaired D L CO in relation to smoking and respiratory symptoms in a middle-aged population. Methods: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, D L CO testing, and high-resolution computed tomography and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) &lt; 0.7. Results: The overall prevalence was 8.8% for CAL, 5.7% for impaired D L CO (DLCO &lt; LLN), and 8.8% for emphysema, with a higher prevalence in current smokers than in ex-smokers and never-smokers. The proportion of never-smokers among those with CAL, emphysema, and impaired D L CO was 32%, 19%, and 31%, respectively. Regardless of smoking habits, the prevalence of respiratory symptoms was higher among people with CAL and impaired D L CO than those with normal lung function. Asthma prevalence in never- smokers with CAL was 14%. In this group, asthma was associated with lower FEV1 and more respiratory symptoms. Conclusions: In this large population-based study of middle-aged people, CAL and impaired D L CO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never- smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD.

AIMS: The aim of the study was to determine whether left ventricular systolic function, in terms of global left ventricular longitudinal strain (GLS), and diastolic function, expressed as the ratio between early diastolic transmitral flow and mitral annular motion velocities (E/e'), can predict cardiovascular events in patients with diabetes mellitus type 2.

METHODS AND RESULTS: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 ± 17 months. Univariate Cox regression analysis showed that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12; 95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated with cardiovascular events independent of age, sex, GLS, left ventricular ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver operating characteristic curves showed that E/e' and HbA1c were the strongest predictors for cardiovascular events, both having an area under the curve (AUC) of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer analysis, the cumulative probability of an event during the follow-up period was 8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with E/e' ≤15, P = 0.011.

CONCLUSION: In middle-aged patients with type 2 diabetes, E/e' is a strong predictor of myocardial infarction and stroke, comparable with HbA1c and superior to GLS and LVEF.

Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight amp;lt; 25 kg/m(2), overweight 25-29 kg/m(2), and obesity amp;gt;= 30 kg/m(2) ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/e (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p amp;lt; 0.05 vs. p amp;lt;0.05). Corresponding results in the control group were 58% (6%) vs. -22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p amp;lt;0.05 vs. p amp;lt;0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n =187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n =179) (p amp;lt;0.05). Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.

Aims. - Elevated body mass index (BMI) is associated with an increased risk of type 2 diabetes and cardiovascular disease (CVD). This study explored the association between BMI changes in the first 18 months of newly diagnosed type 2 diabetes and the risk of long-term CVD mortality. less thanbrgreater than less thanbrgreater thanMethods. - A total of 8486 patients with newly diagnosed type 2 diabetes and no previous history of CVD or cancer were identified from 84 primary-care centres in Sweden. During the first year after diagnosis, patients were grouped according to BMI change: Increase, or andgt;= +1 BMI unit; unchanged, or between +1 and-1 BMI unit; and decrease, or andlt;=-1 BMI unit. Associations between BMI change and CVD mortality, defined as death from stroke, myocardial infarction or sudden death, were estimated using adjusted Cox proportional hazards models (NCT 01121315). less thanbrgreater than less thanbrgreater thanResults. - Baseline mean age was 60.0 years and mean BMI was 30.2 kg/m(2). Patients were followed for up to 9 years (median: 4.6 years). During the first 18 months, 53.4% had no change in their BMI, while 32.2% decreased and 14.4% increased. Compared with patients with unchanged BMI, those with an increased BMI had higher risks of CVD mortality (hazard ratio: 1.63, 95% CI: 1.11-2.39) and all-cause mortality (1.33, 1.01-1.76). BMI decreases had no association with these risks compared with unchanged BMI: 1.06 (0.76-1.48) and 1.06 (0.85-1.33), respectively. less thanbrgreater than less thanbrgreater thanConclusion. - Increased BMI within the first 18 months of type 2 diabetes diagnosis was associated with an increased long-term risk of CVD mortality. However, BMI decrease did not lower the long-term risk of mortality.

Objectives To study the value of combining individual- and neighborhood-level sociodemographic data to predict study participation and assess the effects of baseline selection on the distribution of metabolic risk factors and lifestyle factors in the Swedish CardioPulmonary bioImage Study (SCAPIS). Methods We linked sociodemographic register data to SCAPIS participants (n = 30,154, ages: 50-64 years) and a random sample of the studys target population (n = 59,909). We assessed the classification ability of participation models based on individual-level data, neighborhood-level data, and combinations of both. Standardized mean differences (SMD) were used to examine how reweighting the sample to match the population affected the averages of 32 cardiopulmonary risk factors at baseline. Absolute SMDs &gt; 0.10 were considered meaningful. Results Combining both individual-level and neighborhood-level data gave rise to a model with better classification ability (AUC: 71.3%) than models with only individual-level (AUC: 66.9%) or neighborhood-level data (AUC: 65.5%). We observed a greater change in the distribution of risk factors when we reweighted the participants using both individual and area data. The only meaningful change was related to the (self-reported) frequency of alcohol consumption, which appears to be higher in the SCAPIS sample than in the population. The remaining risk factors did not change meaningfully. Conclusions Both individual- and neighborhood-level characteristics are informative in assessing study selection effects. Future analyses of cardiopulmonary outcomes in the SCAPIS cohort can benefit from our study, though the average impact of selection on risk factor distributions at baseline appears small.

Poor nutritional status is widespread among the elderly and is associated with increased morbidity and mortality. The aim of this study was to longitudinally describe the nutritional status in elderly people living in nursing homes. Nutritional status was recorded longitudinally in elderly people living in 11 different nursing homes in Sweden. Participants were examined at baseline by specially trained nurses who also assisted with questionnaires and collected data for current medical treatment from patient records. Nutritional status was evaluated at baseline and after 24 months with the mini nutritional assessment (MNA). The study included 318 subjects. The mean age of the participants was 85.0 years (range 65-101). At baseline, 41.6% were well nourished, 40.3% at risk of malnutrition, and 17.7% malnourished according to the MNA. Survival was significantly lower in the malnourished group. After 24 months, almost half of the population had died. The group of participants who survived at 24 months represents a population of better nutritional state, where 10.6% were malnourished at baseline increasing to 24.6% after 24 months. After 24 months, 38.7% of the participants showed a decline in nutritional state. The group with deteriorating MNA scores had higher weight, BMI values, and a higher hospitalization rate. The prevalence of malnutrition in nursing home residents increased over time and it is important to evaluate nutritional state regularly. Nutritional interventions should be considered in better nourished groups, as well as in malnourished individuals, to prevent a decline in nutritional state.

Background: Since the burden of care for elderly patients with heart failure (HF) can be decreased by therapeutic measures, it is important that such patients are identified correctly. This study explores the prevalence of HF in nursing homes in Sweden, with special consideration of the risk of failure to diagnose HF in the study population. A second aim is to explore medication and the adherence to guidelines for the treatment of HF. Methods: 429 patients from 11 nursing homes were included during 2008-2011. Information about diagnoses and medications from patient records, blood samples, questionnaire responses and blood pressure measurements were collected. The baseline characteristics of the patients, their medications and one-year mortality were identified and then compared regarding HF diagnosis and B-type natriuretic peptide (BNP) levels. A BNP level of greater than 100 ng/L was used to identify potential cases of HF. Results: The point prevalence of HF diagnosis in the medical records in the study population was 15.4%. With the recommended cut-off value for BNP, up to 196 subjects in the study population (45.7%) qualified for further screening of potential HF. The subjects in the HF and non-HF groups were similar with the exception of mean age, BNP levels and Mini Mental State Examination results which were higher in the HF group, and the eGFR and blood pressure, which were lower when HF. The subjects with higher BNP values were older and had lower eGFR, Hb, diastolic blood pressure and BMI. The subjects with HF diagnoses were in many cases not treated according to the guidelines. Loop diuretics were often used without concomitant ACE inhibitors or angiotensin receptor blockers. The subjects without HF diagnoses in the medical records at inclusion but with BNP values greater than 100 ng/L had less appropriate HF medication. The one-year mortality was 52.9% in the population with HF. Conclusions: Our study suggests that the estimated prevalence of HF in nursing homes in Sweden would increase if BNP measurements were used to select patients for further examinations. The pharmacological treatment of HF varied substantially, as did adherence to guidelines.

Aim: The aim of the present study was to study the renal function and the relationship of deterioration in renal function with major outcomes in elderly nursing home residents. A second aim was to compare the internationally recommended formulae for estimated glomerular filtration rate (eGFR) consisting of both creatinine and cystatin C in a nursing home population. Methods: A total of 429 patients from 11 nursing homes were included during 2008-2011. GFR was estimated, from formulae based on both creatinine and cystatin C, at baseline and after 1 and 2 years. The patients were divided into groups based on chronic kidney disease level, and comparisons were made for mortality, morbidity, the use of medications and between the different formulae for eGFR. Results: Survival was lower in the groups with lower renal function. Over 60% of the residents had impaired renal function. Those with impaired renal function were older, had a higher number of medications and a higher prevalence of heart failure. Higher number of medications was associated with a greater risk of rapid decline in renal function with an odds ratio of 1.2 (95% confidence interval 1.06-1.36, P = 0.003). The compared eGFR formulae based on both cystatin C and creatinine were in excellent concordance with each other. Conclusions: Decreased renal function was associated with increased mortality. A majority of nursing home residents had declining renal function, which should be considered when prescribing medications. The more medications, the higher the risk for rapidly declining renal function.

Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate amp;lt;60 mg/mL/1.73 m(2) and/or urinary albumin-creatinine ratio amp;gt;= 3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline. Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

Aims/hypothesis: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease. Methods: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used. Results: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p &lt; 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p &lt; 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p &lt; 0.01 for all). Both sTNFRs were associated with mortality. Conclusions/Interpretations: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

AIM: Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D).

METHODS: This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality.

RESULTS: Of the total study cohort, 20 patients declined by ≥20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR<60mL/min/1.73m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR)>3g/mol] had higher median levels of endostatin than those without nephropathy (62.7μg/L vs 57.4μg/L, respectively; P=0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (≥20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07).

CONCLUSION: In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.

Aim: Our aim was to investigate in a large population -based cohort study whether increased arterial stiffness and subclinical atherosclerosis in the coronary arteries differ at different stages of dysglycaemia.Methods: Data were obtained from SCAPIS, a population -based cohort of participants 50- 64 years. The study population of 9379 participants was categorised according to glycaemic status: normoglycaemic, pre-diabetes (fasting glucose: 6.1- 6.9 mmol/L and/or HbA1c 6%- 6.4%) and diabetes. Pulse wave velocity (PWV) was measured by the SphygmoCor XCEL system and arterial stiffness was defined by PWV =10 m/s. Coronary artery calcium score (CACS) was assessed by coronary computed tomography and coronary artery calcification was defined by CACS =100.Results: We identified 1964 (21%) participants with dysglycaemia, out of which 742 (7.9%) had diabetes mellitus. PWV =10 m/s was present in 808 (11%), 191 (16%), 200 (27%) and CACS =100 in 801 (11%), 190 (16%), 191 (28%) participants with normoglycaemia, pre-diabetes and diabetes, respectively, all, p &lt; 0.001. The overlap between PWV =10 m/s and CACS =100 within each glycaemic category was 188 (2.5%), 44 (3.6%) and 77 (10) respectively. There was an association between glycaemic status and increased PWV in the fully adjusted models, but not for glycaemic status and CACS =100, where there was no difference for pre-diabetes compared to normoglycaemia, OR 1.2 (95% CI 0.98- 1.4). In the total study population, there was an association between HbA1c and PWV after adjustment, p &lt;0.001.Conclusions: Our results show that increased arterial stiffness and subclinical coronary artery atherosclerosis are present in the early stages of dysglycaemia, but the overlap between markers of major subclinical vascular damage was small in all glycaemic categories. This could be explained by different pathways in the pathogenesis of arterial stiffness or atherosclerosis in the coronary arteries.

Measuring intima-media thickness (IMT) in the common carotid artery (CCA) is a valuable resource for the evaluation of subclinical atherosclerosis. The main objective of this study was to explore whether a B-mode ultrasound technique, Philips ATL, and an M-mode ultrasound technique, Wall Track System (WTS), show interchangeable results when measured in CCA and the abdominal aorta (AA). A total of 24 healthy, young subjects were examined. IMT and lumen diameter (LD) of the AA and the CCA were measured twice by two skilled ultrasonographers with two different ultrasound equipment B-mode: (Philips, ATL and M-mode: WTS).The intra-observer variability of IMT in CCA and AA using B-mode showed a coefficient of variation 8% and 9%, and with M-mode 11% and 15%, respectively. Interobserver variability of IMT in CCA and AA using B-mode was 6% and 12%, and with M-mode 11% and 18%, respectively. CCA IMT was 0·53 ± 0·07 and 0·53 ± 0·09 mm using B-mode and M-mode, respectively. However, in AA, IMT was 0·61 ± 0·5 and 0·54 ± 0·10 mm using B-mode and M-mode, respectively. Thus, AA IMT was 11·5% thicker using B-mode (P<0·01). We received adequate IMT readings from the carotid artery as well as the AA using two commonly used B-mode and M-mode techniques. B-mode technique seems to show less variability, especially in the AA. More importantly, the two techniques measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.

Background

Anthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.

Methods

Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old.

Results

There were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

Conclusions

We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

Aim: The aim of this study was to prospectively explore how laboratory and anthropometric risk factors predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.

Methods: Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55-65 years old.

Results: There were significant correlations between apolipoprotein B (apoB) (r= 0.144, p=0.03), C - reactive protein (CRP) (r=0.172, p=0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r=0.130, p=0.049), waist circumference (WC) (r=0.147, p=0.027) and sagittal Abdominal Diameter (SAD) (r=0.184, p=0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p=0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

Conclusion: We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

The aim of this study was to explore associations between abdominal obesity, inflammatory markers, and subclinical organ damage in 740 patients with type 2 diabetes. Waist circumference (WC) and sagittal abdominal diameter (SAD) was measured. Blood samples were analyzed for; C-reactive protein (CRP), interleukin (IL) -1β and IL-6. Carotid intimamedia thickness (IMT) was evaluated by ultrasonography. Aortic pulse wave velocity (PWV) was measured with applanation tonometry.

Abdominal obesity were significantly correlated with; IL-6, CRP (both p= <0.001, WC and SAD, respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001, for WC and SAD, respectively). In multiple linear regressions with IMT as dependent variable and age, sex, statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, as independent variables, SAD (p=0.047) but not WC, remained associated with IMT. In stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

We conclude that SAD and WC are feasible measures of obesity that provides information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC.

AIMS: To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes. METHODS: We analysed data from 247 patients with Type 2 diabetes, aged 55-66 years, in the Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden. RESULTS: The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA(1c)) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA(1c), hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7-10.8, P = 0.002). CONCLUSIONS: We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

Aims To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes.

Methods We analysed data from 247 patients with Type 2 diabetes, aged 55–66 years, in the Cardiovascular Risk factors in Patients with Diabetes—a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden.

Results The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA_1c) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA_1c, hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7–10.8, P = 0.002).

Conclusions We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

Objectives There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD).

Methods In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55–65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV.

Results Copeptin was associated with TBI (β–0.0020, CI–0.0035– (–0.0005), p = 0.010) and aPWV (β 0.023, CI 0.002–0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking.

Conclusions Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders.

Background: Individuals with diabetes are at higher risk for developing arterial disorders. The toe-brachial index (TBI) is associated with peripheral vascular disease, and aortic pulse-wave velocity (aPWV) is currently the gold standard for assessing arterial stiffness. High concentrations of plasma arginine vasopressin (AVP) preferentially stimulate V1a receptors, which affect the vascular bed and may contribute to cardiovascular (CV) complications. Copeptin, a more stable peptide of AVP, is co-secreted from the pituitary gland in equimolar amounts to AVP upon hemodynamic, osmotic, and other stress-related stimuli. Elevated levels of copeptin are potentially linked to vascular dysfunction.

Objective: To analyze the association of copeptin to TBI and aPWV as a marker of arterial disorder in patients with type 2 diabetes mellitus (T2D).

Methods: A cross-sectional analysis was conducted on 681 patients from the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes – a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) with data on copeptin, TBI, and aPWV. The relationship between the conventional cardiovascular risk factors and copeptin with TBI and aPWV were examined, respectively. Pearson correlation analysis and linear regression analyses were used.

Results: Copeptin correlated to TBI (r=-0.086, P=0.027) and aPWV (r=0.143, P<0,001). Copeptin was also negatively associated with TBI (β=-0.093, P=0.027) and aPWV (β=0.121, P=0.004) independently of age, sex, diabetes duration, BMI, smoking, previous cardiovascular diseases, HbA1c, HDL cholesterol, and estimated glomerular filtration rate.

Conclusion: Copeptin is independently associated with TBI and aPWV. Copeptin may play an important role in the development of arterial disorders. Measuring copeptin levels may be a simpler method and more efficient way to identify individuals at risk for arterial disorders compared to current methods such as TBI and aPWV.

Objective: In non-alcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers.

Methods: In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistica lapproach.

Results: In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2.

Conclusion: MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling.

Background: Different regional depots of fat have distinct metabolic properties and may relate differently to adverse cardiac remodeling. We sought to quantify regional depots of body fat and to investigate their relationship to cardiac structure and function in Type 2 Diabetes (T2D) and controls.

Methods: From the SCAPIS cohort in Linköping, Sweden, we recruited 92 subjects (35% female, mean age 59.5 ± 4.6 years): 46 with T2D and 46 matched controls. In addition to the core SCAPIS data collection, participants underwent a comprehensive magnetic resonance imaging examination at 1.5 T for assessment of left ventricular (LV) structure and function (end-diastolic volume, mass, concentricity, ejection fraction), as well as regional body composition (liver proton density fat fraction, visceral adipose tissue, abdominal subcutaneous adipose tissue, thigh muscle fat infiltration, fat tissue-free thigh muscle volume and epicardial adipose tissue).

Results: Compared to the control group, the T2D group had increased: visceral adipose tissue volume index (P < 0.001), liver fat percentage (P < 0.001), thigh muscle fat infiltration percentage (P = 0.02), LV concentricity (P < 0.001) and LV E/e'-ratio (P < 0.001). In a multiple linear regression analysis, a negative association between liver fat percentage and LV mass (St Beta -0.23, P < 0.05) as well as LV end-diastolic volume (St Beta -0.27, P < 0.05) was found. Epicardial adipose tissue volume and abdominal subcutaneous adipose tissue volume index were the only parameters of fat associated with LV diastolic dysfunction (E/e'-ratio) (St Beta 0.24, P < 0.05; St Beta 0.34, P < 0.01, respectively). In a multivariate logistic regression analysis, only visceral adipose tissue volume index was significantly associated with T2D, with an odds ratio for T2D of 3.01 (95% CI 1.28-7.05, P < 0.05) per L/m² increase in visceral adipose tissue volume.

Conclusions: Ectopic fat is predominantly associated with cardiac remodeling, independently of type 2 diabetes. Intriguingly, liver fat appears to be related to LV structure independently of VAT, while epicardial fat is linked to impaired LV diastolic function. Visceral fat is associated with T2D independently of liver fat and abdominal subcutaneous adipose tissue.

Objectives The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours. Design Cross-sectional. Setting Multisite study at university hospitals. Participants A total of 22670 participants without cardiovascular disease (51%women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer. Primary and secondary outcomes Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound. Results High daily SED (&gt;70% approximate to 10.5hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (&gt;55% approximate to 8hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, &gt;2% approximate to 20min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73). Conclusions MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.

The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50-64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an "at-risk" behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.

Introduction Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) amp;gt;30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear. Methods This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score amp;gt;= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. Results We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; pamp;lt;0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. Conclusion Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Background

The objective was to explore the usefulness of the morbidity risk adjustment system Adjusted Clinical Groups^® (ACG), in comparison with age and gender, in explaining and estimating patient costs on an individual level in Swedish primary health care. Data were retrieved from two primary health care centres in southeastern Sweden.

Methods

A cross-sectional observational study. Data from electronic patient registers from the two centres were retrieved for 2001 and 2002, and patients were grouped into ACGs, expressing the individual combination of diagnoses and thus the comorbidity. Costs per patient were calculated for both years in both centres. Cost data from one centre were used to create ACG weights. These weights were then applied to patients at the other centre. Correlations between individual patient costs, age, gender and ACG weights were studied. Multiple linear regression analyses were performed in order to explain and estimate patient costs.

Results

The variation in individual patient costs was substantial within age groups as well as within ACG weight groups. About 37.7% of the individual patient costs could be explained by ACG weights, and age and gender added about 0.8%. The individual patient costs in 2001 estimated 22.0% of patient costs in 2002, whereas ACG weights estimated 14.3%.

Conclusion

ACGs was an important factor in explaining and estimating individual patient costs in primary health care. Costs were explained to only a minor extent by age and gender. However, the usefulness of the ACG system appears to be sensitive to the accuracy of classification and coding of diagnoses by physicians.

Abstract

Knowledge about the need for care of elderly individuals in community dwellings and the factors affecting their needs and support is limited. The aim of this study was to characterize the frailty of a population of elderly individuals living in community dwellings in Sweden in relation to co-morbidity, use of drugs, and risk of severe conditions such as malnutrition, pressure ulcers, and falls. In 2008, 315 elderly individuals living in community dwellings were interviewed and examined as part of the SHADES-study. The elderly demonstrated co-morbidity (a mean of three diseases) and polypharmacy (an average of seven drugs). More than half the sample was at risk for malnutrition, one third was at risk for developing pressure ulcers, and nearly all (93%) had an increased risk of falling and a great majority had cognitive problems. Age, pulse pressure, body mass index, and specific items from the modified Norton scale (MNS), the Downton fall risk index (DFRI), and the mini nutritional assessment (MNA-SF) were related to different outcomes, defining the need for care and frailty. Based on the results of this study, we suggest a single set of items useful for understanding the need for care and to improve individual based care in community dwellings.

Long term stress exposure is typical for modern societies and might trigger different diseases. This case-control study reveals that persons who had suffered an acute myocardial infarction (AMI) had elevated cortisol concentrations in the month before the acute event. Middle-aged patients admitted to cardiology clinics with acute myocardial infarction (AMI) (n=174) were compared to 3156 controls from a population-based cohort in southeast Sweden. The median Hair Cortisol Concentrations (HCC) for those who had suffered an AMI was 53.2 pg/mg compared to 22.2 pg/mg for the control group (p&lt;0.001). In bivariate analysis, higher levels of HCC were strongly (OR=5.69) and statistically significantly associated with current AMI status. The discrimination of cases with AMI from controls remained statistically significant (OR=5.04) even after controlling for established cardiovascular risk factors in a multivariate analysis. Middle-aged persons with acute myocardial infarction had significantly elevated cortisol levels during the month before the cardiac event. This was evident for both men and women. The biomarker cortisol concentration was independently and statistically significantly related to AMI. Chronic stress seems to be a new promising risk factor for AMI.

Background and aims: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. Methods: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. Results: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 +/- 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean +/- SD change of 2.9 +/- 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p &lt; 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). Conclusions: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.

The interaction of the PPARγ Pro12Ala polymorphism with diabetes and cardiovascular risk is controversial. We studied 173 women and 309 men in the observational CARDIPP trial in which determination of left ventricular mass, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were performed. Blood pressures were measured with 24-h ambulatory technique (ABP). Heterozygotes and homozygotes of Ala were defined as Ala in the analyses. Men with Ala-isoform displayed higher waist circumference (Ala: 107 ± 14 cm, Pro: 104 ± 11 cm, p = 0.045) and body weight (Ala: 95.7 ± 18 kg, Pro: 91.6 ± 14 kg, p = 0.042) than Pro-homozygotes. Men with ALA-isoform also showed higher systolic ABP levels (Ala: 134 ± 15 mmHg, Pro: 130 ± 14 mmHg, p = 0.004), whereas left ventricular mass index, IMT and PWV were unrelated to isoforms. In contrast, carotid–radial PWV was lower in women with the Ala-isoform (Ala: 7.9 ± 1.0 m/s, Pro: 8.5 ± 1.3 m/s, p = 0.01) and levels of apolipoprotein A1 were higher (Ala: 1.43 ± 0.27 g/l, Pro: 1.35 ± 0.17 g/l, p = 0.03). In conclusion, we found that men with type 2 diabetes having the Ala-isoform of PPARγ Pro12Ala had an unfavorable cardiovascular risk profile, whereas women with this isoform had lower carotid–radial PWV and higher apolipoprotein A1 levels suggesting a beneficial prognosis. These differences according to gender of the ALA isoform in type 2 diabetes deserve further attention.

Background: The interaction of the PPARγ Pro12Ala with obesity and cardiovascular risk is controversial. We aimed to study potential associations of the Ala isoform of this polymorphism with obesity, blood pressure and markers of cardiovascular disease and organ damage in middle aged patients with type 2 diabetes.

Subjects and methods: We recruited 148 women and 246 men in the CArdiovascular Risk factors in Patients with DIabetes – a Prospective study in the Primary health care setting (CARDIPP) study in which early markers of organ damage by cardiac echocardiography, determination of carotid intima media thickness (IMT) and measurement of pulse wave velocity (PWV) was performed. Blood pressures were measured as both as 24-hour ambulatory blood pressure and as a noninvasive recording of central blood pressure. Allelic discrimination was detected with the ABI prism 7500HT Sequence Detection System. Due to the low prevalence of Ala homozygotes, heterozygotes and homozygotes of Ala were defined as Ala isoform in the analyses.

Results: Men with Ala isoform exhibited higher sagittal abdominal diameter (Pro: 25.4±3.4 cm, Ala: 26.7±4.9 cm, p= 0.04) waist circumference (Pro: 104±11 cm, Ala: 108±15 cm, p= 0.046) and body weight (Pro: 91.6±14, Ala: 96.5±18, p= 0.035) than homozygotes for the Pro isoform. However, there were no differences in either gender with respect to blood pressures, left-ventricular mass-index, carotid IMT or carotid-femoral PWV in the participants.

Conclusion: It is unlikely that determination of the PPARγ Pro12Ala isoform in clinic practice adds any major information on cardiovascular risk or circulatory organ damage in patients with type 2 diabetes.

OBJECTIVE-To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS-The skin blood flow response to local heating (44 degrees C for 20 mm) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity X concentration), in a physiologically relevant unit (grams RBC per 100 g tissue X millimeters per second) in a fixed output volume, separated into three velocity regions: v less than1 mm/s, v 1-10 mm/s, and v greater than10 mm/s. RESULTS-The increased blood flow occurs in vessels with a velocity greater than1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v greater than10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v greater than10 mm/s, whereas no significant increase was found for v less than1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS-The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio.

The response to local heating (44^oC for 20 min) was evaluated in 28 type 2 diabetes patients (DM) and 29 non-diabetes controls (ND). Microcirculatory perfusion was assessed using conventional and quantitative Laser Doppler flowmetry (cLDF and qLDF), respectively. The qLDF estimates perfusion in a physiological relevant unit (g RBC / 100 g tissue × mm/s) in a fixed output volume, separated into three velocity regions, v < 1 mm/s, 1 - 10 mm/s, and v > 10 mm/s. Perfusion in cLDF is given in arbitrary units with unknown velocity distribution and measurement volume.

A significantly lower response in DM than in ND was found after heat provocation both for the initial peak and the plateau response, while no significant differences were found at baseline. The qLDF showed increased perfusion for the velocity regions 1-10 mm/s and above 10 mm/s, while no significant increase was found for v < 1 mm/s. In conclusion, we found a lowered LDF response to local heating in DM. The new qLDF method showed that the increased blood flow occurs in vessels with a velocity above 1 mm/s. Baseline qLDF-data indicated that a redistribution of flow to higher velocity regions was associated with longer DM duration and for DM a negative correlation between perfusion and BMI.

Aim: The aim of this study was to investigate the association between plasma MR-proANP and cardiovascular disease (CVD) in a middle-aged population with type 2 diabetes. Methods: MR-proANP was measured in 690 patients with type 2 diabetes participating in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care). The outcome variables were incident major adverse cardiovascular events (MACE) and all-cause mortality. Patients were followed using the national Swedish Cause of Death Registry and the Inpatient Register. Results: During the mean follow-up period of 10.8 years, MACE occurred in 111 patients and 102 patients died. The hazard ratio for an increment of MR-proANP of 1 pmol/l adjusted for sex, age, current smoking, previous CVD, HbA1c, serum cholesterol, eGFR, systolic blood pressure, C-reactive protein, aortic pulse wave velocity, left ventricular mass and intima media thickness in the carotid arteries was 1.007 (95% CI 1.000-1.013, P = 0.042) for MACE and 1.008 (95% CI 1.001-1.014, P = 0.017) for all-cause mortality. Conclusions: Elevated MR-proANP levels predict an increased risk for MACE and all-cause mortality in patients with type 2 diabetes independently of CVD risk factors and markers for subclinical organ damage. (c) 2021 Elsevier B.V. All rights reserved.

Background: Dyslipidaemia in patients with diabetes contributes to the risk of atherosclerotic cardiovascular disease. We aimed to identify a dyslipidemic profile associated with both dysglycemia and subclinical coronary atherosclerosis. Methods: Study participants (n = 5050) were classified in three groups: normoglycemia, pre-diabetes, and diabetes. A coronary artery calcium score (CACS) &gt; 0 defined subclinical coronary atherosclerosis. Two independent methods were used to identify, among 225 lipid biomarkers, those that were associated with pre-diabetes and diabetes and were further tested for association by zero inflated Poisson regression with CACS and with CACS burden in study participants with CACS&gt;0. Estimates were adjusted for cardiovascular risk factors with an interaction term for dispensed lipid lowering drugs. Results: Thirty-two biomarkers associated with prediabetes and diabetes were further investigated for association with CACS. HDL diameter [multi-adjusted OR of 0.85 and 95 %CI (0.78-0.92)] as well as free cholesterol, phospholipids and total lipids in extra large HDL were inversely associated with CACS. There was a borderline significant interaction between small HDL and dispensed lipid lowering drugs on the presence of CACS, with and multi-adjusted OR of 0.53 and 95 %CI (0.36-0.77). None of the 32 glycemic profile-related lipid biomarkers associated with the relative increase of CACS in those with CACS&gt;0. No consistent association was observed between non-HDL lipoproteins and CACS. Conclusions: Changes in composition and relative concentration of HDL associated with both dysglycemia and subclinical coronary atherosclerosis. Treatment with lipid lowering drugs may contribute to reduce the risk associated with high circulating levels of small HDL.