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.

Background

Carotid and coronary atherosclerosis are critical determinants of cardiovascular risk, yet their interrelationship in middle-aged populations is incompletely understood. This study assessed carotid plaque composition, risk-factor associations, coronary disease, and sex differences in a subclinical cohort.

Methods

Within the Swedish CArdioPulmonary bioImage Study (SCAPIS), 533 asymptomatic individuals aged 50–64 years with carotid plaque ≥2.7 mm on ultrasound underwent 3 T multi-contrast carotid cardiovascular magnetic resonance (CMR) and coronary computed tomography angiography. Carotid plaque characteristics were determined manually using established criteria on multi-contrast weighted carotid CMR. Bayesian regression models evaluated associations between cardiovascular risk factors and coronary atherosclerosis.

Results

Lipid rich necrotic core (LRNC) was present in 60% and intraplaque hemorrhage (IPH) in 5.4%; calcification occurred in 48.6%. Maximum carotid wall thickness was 1.8 (1.6-2.0) mm, and mean lumen area 31.3 (26.7-36.1) mm². Coronary atherosclerosis was present in 63.6% of participants, with ≥50% stenosis in 12.9%, and coronary artery calcium score >400 in 12.8%. Men (N=367) had larger carotid lumen area, mean wall area, and maximum wall thickness (all p < 0.001) than women (N=166), differences that persisted after body-surface-area adjustment (all p < 0.01). LRNC was present in 66% of men compared to 47% of women (p < 0.001). LRNC presence was not associated with coronary atherosclerosis, whereas IPH was associated with coronary involvement.

Conclusion

In middle-aged individuals, distinct cardiovascular risk factors were positively linked to presence and volume of LRNC and calcified plaques. The substantial prevalence of high-risk plaque features, particularly LRNC and especially in men, highlights a significant subclinical carotid disease burden.

Lay summary

This study used state-of-the-art magnetic resonance imaging to characterize atherosclerotic plaques in the carotid arteries in middle-aged individuals without clinical cardiovascular disease, offering the following insight into early, subclinical atherosclerosis:

Lipid rich necrotic core (LRNC), a marker of high-risk plaques, was present in 60% of participants with carotid plaques, suggesting a substantial burden of potentially vulnerable atherosclerosis even in asymptomatic individuals.Carotid plaque features such as increased wall thickness, calcification, and presence of LRNC were variably associated with cardiovascular risk factors and plaques with increased wall area, wall thickness, and calcium showed correlations with coronary artery calcium and plaque burden on CT, indicating systemic atherosclerotic involvement.

Background: Arterial mechanics are crucial to cardiovascular functionality. The pressure–strain elastic modulus often delineates mechanical properties. Emerging methods use non-linear continuum mechanics and non-convex minimization to identify tissue-specific parameters in vivo. Reliability of these methods, particularly their accuracy in representing the in vivo stress state, is a significant concern. This study aims to compare the predicted stress state and the collagen-attributed load-bearing fraction with the stress state from in silico experiments. Methods: Our team has evaluated an in vivo parameter identification method through in silico experiments involving finite element models and demonstrated good agreement with the parameters of a healthy abdominal aorta. Results: The findings suggest that the circumferential stress state is well represented for an abdominal aorta with a low transmural stress gradient. Larger discrepancies are observed in the axial direction. The agreement deteriorates in both directions with an increasing transmural stress gradient, attributed to the membrane model’s inability to capture transmural gradients. The collagen-attributed load-bearing fraction is well predicted, particularly in the circumferential direction. Conclusions: These findings underscore the importance of investigating both isotropic and anisotropic aspects of the vessel wall. This evaluation advances the parameter identification method towards clinical application as a potential tool for assessing arterial mechanics.

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: 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: The prevalence of aortic valve stenosis (AS) is increasing due to an ageing population. Despite that right ventricular function has prognostic value for postoperative outcome, the right ventricle (RV) is not extensively studied and often not routinely assessed in AS. Our aim was to explore the relation between severe AS and RV function in a surgical aortic valve replacement (SAVR) cohort, comparing two imaging modalities for RV evaluation.Methods: Patients with severe AS, underwent cardiovascular magnetic resonance imaging (CMR) and transthoracic echocardiography (TTE) before SAVR. RV dysfunction was defined as one or more of the following: tricuspid annular plane systolic excursion (TAPSE) &lt; 17 mm, RV free wall strain (RVFWS) &gt; -20% by TTE and RV ejection fraction (RVEF) &lt;50% by CMR.Results: Sixteen (33%) patients were found to have RV dysfunction. Patients with RV dysfunction showed significantly lower indexed aortic valve area, left ventricular (LV) ejection fraction as well as RV and LV stroke volumes compared to patients with maintained RV function. All patients with reduced RVEF also had changes in TAPSE or RVFWS and a larger number of patients had a reduced longitudinal RV function despite a normal RVEF.Conclusion: In a SAVR cohort one-third of the patients had RV dysfunction, defined by RVEF, TAPSE or RVFW strain. Echocardiography detected subtle changes in RV function before RVEF was reduced. It is likely that the more pronounced the AS, the more frequent the occurrence of RV dysfunction.

Aims Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic haemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR), and circulating biomarkers in aortic dilation. Methods and results Forty-seven cases with aortic dilation (diameter &gt;= 40 mm) and 50 sex-and age-matched controls (diameter &lt; 40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D flow CMR, and biomarkers including interleukin-6, collagen type I alpha 1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared with controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between haemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, P &lt; 0.001), and maximum oscillatory shear index and collagen type I alpha 1 chain (r = -0.575, P &lt; 0.001 in cases). Conclusion Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between haemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.

Background: Wall stress of the abdominal aorta (AA) appears to be an important factor in the assessment of risk for rupture based on the relationship between blood pressure and aortic diameter. We therefore investigated peak wall stress as well as isotropic and anisotropic wall stress of AA.Methods: Thirty healthy adults (male = 15) were included. Pulsatile diameter changes were determined non-invasively by an echo-tracking system, and intra-aortic pressure was measured simultaneously. A computer based mechanical model was used to compute the isotropic and anisotropic components of circumferential and longitudinal stresses.Results: Elderly males had higher total wall stress and a higher isotropic stress component in the circumferential direction and higher total longitudinal wall stress than elderly females. The isotropic component increased with age in males but not in females, whereas the anisotropic component decreased with age in both sexes.Conclusion: We found that isotropic and anisotropic properties of the abdominal aortic wall differ between young and elderly participants and between the sexes. A possible explanation could relate to chemical alterations (e.g., due to sex hormones) and changes over time in the physical distribution of fibers. Modeling of wall stress components of the human AA may contribute to a better understanding of elastin-collagen interactions during remodeling of the aortic wall.