Introduction: Hypertension is linked to endothelial dysfunction, but causality and direction is not entirely known. The aim was to study the cross-sectional associations between home, office, and central BP and microcirculatory peak oxygen saturation (OxyP). Methods: In the observational Swedish CArdioPulmonary bioImage Study (SCAPIS) Linköping subsample, office and home BP were measured using an oscillometric device and OxyP was measured in forearm skin after a 5-min occlusion of the brachial artery. A linear regression was fitted to evaluate the mean change in OxyP per SD increase in BP. A logistic regression was fitted to evaluate the associations between BP above the median and OxyP below the median. Results: Of participants, 3,291 were included in the analyses. Per SD increase in systolic home BP, the adjusted mean (95% CI) difference in OxyP was −0.4 (−0.6 to −0.1%). In subgroup analyses, the association remained for women but not men, although the interaction by sex was not statistically significant. Also, in women but not in men, OxyP was lower in those with white coat hypertension vs. sustained normotension, i.e., mean (95% CI) 88.8 (88.2–89.4%) vs. 89.6 (89.3–90.0%), and in those with masked hypertension vs. sustained normotension, i.e., 87.5 (85.9–89.1%) vs. 89.6 (89.3–90.0%). Conclusion: Home BP, which better predicts cardiovascular disease than office BP, was inversely associated with OxyP. This correlation remained in subgroup analyses of women but not men, suggesting possible sex-dependent microcirculatory dysfunction or that masked hypertension could be a more important cardiovascular risk marker in women, despite its higher prevalence in men.

Objectives

Use of snus, including tobacco and nicotine pouches, is increasing in many countries. Nicotine increases blood pressure (BP) acutely, but the long-term effects of quitting the regular use of snus pouches are unknown. The aim was to evaluate the effects of snus cessation on home BP and markers of the metabolic syndrome.

Methods

Volunteers aged 18–70 years using snus daily were invited to abruptly end their snus intake and followed using home BP and metabolic measurements before and for 12 weeks after cessation.

Results

Fifty volunteers were recruited. Of these, 46 (92%) attempted snus cessation and 37 (74%) did not use snus for at least 3 weeks and were included in the study. Of those included, 33 maintained snus cessation for all 12 weeks. The mean age was 38 (± 10) years and 24 (65%) were men. At week 12, the mean changes in systolic home BP was 3.7 (95% CI 1.5–5.9) mmHg, in body weight was 1.8 (95% CI 1.1–2.4) kg, and in HbA1c was 0.7 (95% CI 0.0–1.6) mmol/mol.

Conclusions

Cessation of tobacco and nicotine pouches in individuals who regularly used snus negatively impacted systolic home BP, body weight and HbA1c after 12 weeks. Whether these effects would be reversed by snus re-initiation cannot be determined by this study, but our novel findings suggest that successful cessation of regular snus usage does not immediate improve these cardiovascular risk factors. We call for further research to confirm our findings and evaluate the effects over longer time frames.

Background and aim: Cardiovascular disease (CVD) is the major cause of death in patients with type 2 diabetes mellitus (T2DM), making it of interest to attain efficient methods for prognostic purposes. We aimed to prospectively investigate the association between plasma copeptin and cardiovascular disease (CVD) in individuals with type 2 diabetes mellitus (T2DM), adjusting for mean 24-h ambulatory blood pressure, left ventricular mass index, and traditional cardio-metabolic risk factors.

Methods and results: A cohort of 523 patients with T2DM with complete data on copeptin, age, sex, body mass index (BMI), smoking, total cholesterol, eGFR, HbA1c, 24-h ambulatory systolic blood pressure (24-h SBP), and left ventricular mass index (LVMI) was derived from the Cardiovascular Risk Factors in Patients with Diabetes - a Prospective Study in Primary Care (CARDIPP) study. The incidence of major adverse cardiovascular events (MACE) and all-cause mortality were obtained from the Swedish Cause of Death Registry and the Inpatient Register. A Cox-proportional hazard analysis was conducted. Over 15 years, 120 patients had MACE, while 122 died of any cause. Patients with a copeptin level of ≥5.6 pmol/L exhibited a 2.05 hazard ratio (HR) for MACE (95 % CI 1.24-3.37, p < 0.005). However, after adjustment, no significant association with all-cause mortality (HR 1.30, 95 % CI 0.84-2.02, p = 0.238) was noted. These findings were independent of traditional cardio-metabolic risk factors, 24-h SBP, and LVMI.

Conclusions: Elevated copeptin levels (≥5.6 pmol/L) in patients with T2DM were independently associated with an increased risk of MACE. Measuring plasma copeptin may help identify high-risk T2DM patients.

Background

Licorice, through the effects of glycyrrhizic acid (GA), raises blood pressure (BP). The World Health Organization has suggested that 100 mg GA/d would be unlikely to cause adverse effects, but of 13 previously published studies none have been randomized and controlled and independently quantified the GA content.

Objective

Our aim was to analyze the effects on home BP of a daily licorice intake containing 100 mg GA.

Methods

Healthy volunteers were randomly assigned to start with either licorice or a control product in a nonblinded, 2 × 2 crossover study. Home BP was measured daily, and blood samples were collected at the end of each 2-wk period.

Results

There were 28 participants and no dropouts. The median age was 24.0 y (interquartile range 22.8–27.0 y). During the licorice compared with control intake period, the systolic home BP increased [mean difference: 3.1 mm Hg (95% confidence interval [CI]: 0.8, 5.4 mm Hg) compared with −0.3 mm Hg (95% CI: −1.8, 1.3 mm Hg); P = 0.018] and renin and aldosterone were suppressed [mean change: −30.0% (95% CI: −56.7%, −3.3%) compared with 15.8% (95% CI: −12.8%, 44.4%); P = 0.003; and −45.1% (95% CI: −61.5%, −28.7%) compared with 8.2% (95% CI: −14.7%, 31.1%); P <0.001, respectively]. In the quartile of participants with the most pronounced suppression of renin and aldosterone, N-terminal prohormone of brain natriuretic peptide concentration increased during the licorice compared with control period [mean change: 204.1% (95% CI: −11.6%, 419.7%) compared with 72.4% (95% CI: −52.2%, 197.1%); P = 0.016].

Conclusions

We found licorice to be more potent than previously known, with significant increases in BP, after a daily intake of only 100 mg GA. Thus, the safe limit of intake of this substance might need to be reconsidered.

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.

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: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.

Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.

Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.

Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.

Background: Predicting the risk of readmission or death in patients at the emergency department (ED) is essential in identifying patients who would benefit the most from interventions. We aimed to explore the prognostic value of mid-regional proadrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and high-sensitivity troponin T (hs-TnT) to identify patients with a higher risk of readmission and death among patients presenting with chest pain (CP) and/or shortness of breath (SOB) in the ED.

Methods: This single-center prospective observational study included non-critically ill adult patients with a chief complaint of CP and/or SOB who visited the ED at Linköping University Hospital. Baseline data and blood samples were collected, and patients were followed up for 90 days after inclusion. The primary outcome was a composite of readmission and/or death from non-traumatic causes within 90 days of inclusion. Binary logistic regression was used and receiver operating characteristics (ROC) curves were constructed to determine the prognostic performance for predicting readmission and/or death within 90 days.

Results: A total of 313 patients were included and 64 (20.4%) met the primary endpoint. MR-proADM > 0.75 pmol/L (odds ratio [OR]: 2.361 [95% confidence interval [CI]: 1.031 – 5.407], P = 0.042) and multimorbidity (OR: 2.647 [95% CI: 1.282 – 5.469], P = 0.009) were significantly associated with readmission and/or death within 90 days. MR-proADM increased predictive value in the ROC analysis to age, sex, and multimorbidity (P = 0.006).

Conclusions: In non-critically ill patients with CP and/or SOB in the ED, MR-proADM and multimorbidity may be helpful for the prediction of the risk of readmission and/or death within 90 days.

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.