Four-dimensional flow (4D Flow) CMR affords comprehensive 3D maps of advanced hemodynamics parameters such as wall shear stress (WSS). However, the evaluation of these data is often restricted to spatial averages in large regions of interests, such as the ascending aorta. Recent studies have explored ways of analyzing local intercohort WSS differences by using basic statistical tests with a p-value of 0.05 for determining significance, thus not accounting for the large number of comparisons made when exploring differences for multiple locations across the ascending aorta surface.

Permutation tests, frequently used in brain MRI, permit statistical analysis on a local level while controlling for the family-wise error rate by constructing the null hypothesis distribution based on the maximum statistic over the voxels at each permutation. We sought to use permutation tests to identify local regions of abnormal WSS in the ascending aorta in patients with aortic dilation.

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.

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.

The pro-inflammatory and regulatory roles of T lymphocytes in atherosclerosis are well established but less is known about natural killer (NK) cells and natural killer T (NKT)-like cells. The effects of cardiovascular risk management on the phenotypes of these cells are unknown. To assess changes in NK cell and lymphocyte phenotypes and circulating inflammatory proteins in response to cardiovascular risk management in patients with carotid atherosclerosis. Fifty patients were included in a prospective clinical study. Measurements were at baseline and after 12 months of cardiovascular risk management. Circulating NK, NKT-like and T lymphocyte subpopulations were phenotyped by multi-colour flow cytometry. Proximity extension assay was performed for 176 plasma proteins associated with inflammation and cardiovascular disease. At 12 months there were significant reductions in LDL (P=0.001) and blood pressure (P=0.028). NK cells responded with a reduction in pro-inflammatory (NKG2C(+)) cells (P=0.0003), an increase in anti-inflammatory (NKG2A(+)) cells (P=0.032), and a reduction in terminally differentiated (CD57(+)) NK cells. NKT-like cells showed a similar decrease in terminally differentiated subpopulations (P=0.000002). Subpopulations of T helper cells exhibited a significant reduction in central memory (P=1.09x10(-8)) and a significant increase in CD4(+) naive- (P=0.0008) and effector memory T cells (P=0.006). The protein analysis indicated that cardiovascular risk management affects proteins involved in the inflammatory NF-kappa B pathway. The consistent decrease in senescent phenotypes of NK, NKT-like and CD4(+) cells with a concomitant increase in more naive, phenotypes suggests a change towards a less pro-inflammatory lymphocyte profile in response to cardiovascular risk management.Trial registry name: CARotid MRI of Atherosclerosis (CARMA). ClinicalTrials.gov identifier NCT04835571 (08/04/2021). https://www.clinicaltrials.gov/study/NCT04835571.

OBJECTIVES: To investigate the association between type I collagen α1 chain (COL1α1) levels and coronary artery disease (CAD) by using absolute quantification in plasma. Also, to investigate the correlates of COL1α1 to clinical characteristics and circulating markers of collagen metabolism.

DESIGN: Life conditions, Stress and Health (LSH) study: prospective cohort study, here with a nested case-control design.Assessing Platelet Activity in Coronary Heart Disease (APACHE) study: prospective cohort study.

SETTING: LSH: primary care setting, southeast Sweden.APACHE: cardiology department, university hospital, southeast Sweden.

PARTICIPANTS: LSH: 1007 randomly recruited individuals aged 45-69 (50% women). Exclusion criteria was serious disease. After 13 years of follow-up, 86 cases with primary endpoint were identified and sex-matched/age-matched to 184 controls.

APACHE: 125 patients with myocardial infarction (MI), 73 with ST-elevation MI and 52 with non-ST-elevation MI.

EXCLUSION CRITERIA: Intervention study participation, warfarin treatment and short life expectancy.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the association between baseline COL1α1 and first-time major event of CAD, defined as fatal/non-fatal MI or coronary revascularisation after 13 years. Secondary outcomes were the association between the collagen biomarkers PRO-C1 (N-terminal pro-peptide of type I collagen)/C1M (matrix metalloproteinase-mediated degradation of type I collagen) and CAD; temporal change of COL1α1 after acute MI up to 6 months and lastly, correlates between COL1α1 and patient characteristics along with circulating markers of collagen metabolism.

RESULTS: COL1α1 levels were associated with CAD, both unadjusted (HR=0.69, 95% CI=0.56 to 0.87) and adjusted (HR=0.55, 95% CI=0.41 to 0.75). PRO-C1 was associated with CAD, unadjusted (HR=0.62, 95% CI=0.47 to 0.82) and adjusted (HR=0.61, 95% CI=0.43 to 0.86), while C1M was not. In patients with MI, COL1α1 remained unchanged up to 6 months. COL1α1 was correlated to PRO-C1, but not to C1M.

CONCLUSIONS: Plasma COL1α1 was independently and inversely associated with CAD. Furthermore, COL1α1 appeared to reflect collagen synthesis but not degradation. Future studies are needed to confirm whether COL1α1 is a clinically useful biomarker of CAD.

Aims: Dilation of the ascending aorta (AA) is often asymptomatic until a life-threatening dissection or rupture occurs. An overall increase in the use of thoracic imaging has enabled early and sometimes incidental identification of AA dilation. Still, the prevalence and determinants of AA dilation remain to be clarified. The aim was to identify and characterize persons with AA dilation in a middle-aged Swedish population.

Methods and results: We used the Swedish CardioPulmonary BioImage Study Linköping (n = 5058, age 50-65 years) to identify cases with AA diameter ≥ 40 mm on coronary computed tomography angiography (CCTA) or chest computed tomography. Age- and gender-matched individuals with AA diameter < 40 mm served as controls. Echocardiography, blood pressure (BP) measurements (office and home), pulse wave velocity (PWV), coronary artery calcification (CAC), CCTA-detected coronary atherosclerosis, and carotid ultrasound were used to characterize these subjects. We identified 70 cases (mean AA diameter 44 mm, 77% men) and matched these to 146 controls (mean AA diameter 34 mm). Bicuspid aortic valve and aortic valve dysfunction were more common in cases than in controls (8% vs. 0% and 39% vs. 11%, respectively). Both office and home BP levels were significantly higher among cases. Also, high PWV (>10 m/s) levels were more common in cases (33% vs. 17%). Neither CAC scores nor prevalence or burden of atherosclerosis in coronary and carotid arteries differed between groups.

Conclusion: The prevalence of dilated AA was 1.4% and showed positive associations with male gender, aortic valve pathology, and diastolic BP, though not with subclinical atherosclerosis.

Lutein is a dietary lipophilic compound with anti-inflammatory properties. We havepreviously shown that dairy fat can improve the lutein content in spinach smoothies. It is, however,unclear whether fat concentrations and fermentation status in dairy products affect lutein liberation insmoothies. Moreover, plant-based milks vary in fat, protein, and fiber content which may affect luteindissolution. This study aimed to provide translatable information to consumers by comparing luteinliberation in spinach smoothies made with different dairy or plant-based liquids in domestic settings.The smoothies were digested in vitro, and liberated lutein was measured by high-performance liquidchromatography (HPLC). High-fat and medium-fat cow’s milk, as well as coconut milk with andwithout additives, were found to significantly improve lutein liberation by 36%, 30%, 25%, and 42%,respectively, compared to blending spinach with water alone. Adjustment models suggested thatthe effects of cow’s milk and coconut milk were derived from fat and protein, respectively. On theother hand, soymilk with and without additives showed significantly reduced lutein liberation by40% and 61%, respectively. To summarize, only 4 out of 14 tested liquids increased lutein liberationin spinach smoothies. The results highlight the importance of testing food companions for lipophilicactive ingredients.

)Several earlier studies have reported increased risk of bleeding in women with myocardial infarction, (MI) compared to men. The reasons for the observed difference are incompletely understood, but one suggested explanation has been excess dosing of antithrombotic drugs in women. The aim of this prospective observational study was to assess sex differences in platelet activity in patients treated with three different platelet inhibitors. We recruited 125 patients (37 women and 88 men) with MI, scheduled for coronary angiography. All patients received clopidogrel and aspirin. A subgroup of patients received glycoprotein (GP) IIb/IIIa-inhibitor. Platelet aggregation in whole blood was assessed at several time points, using impedance aggregometry. SolubleP-selectin was measured 3 days after admission. There were no significant differences between women and men in baseline features or comorbidities except higher frequency of diabetes, lower hemoglobin value, and lower estimated glomerular filtration rate, in women on admission. We observed significantly more in-hospital bleeding events in women compared to men (18.9% vs. 6.8%,p= .04). There were no differences in platelet aggregation using three different agonists, reflecting treatment effect of GPIIb/IIIa-inhibitors, clopidogrel, and aspirin, 6-8 hours, 3 days, 7-9 days, or 6 months after loading dose. Moreover, there was no significant difference in solubleP-selectin. The main finding of this study was a consistent lack of difference between the sexes in platelet aggregation, using three different agonists at several time-points. Our results do not support excess dosing of anti-platelet drugs as a major explanation for increased bleeding risk in women.

Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the arterial wall. The biologic composition of an atherosclerotic plaque determines whether the plaque is more or less vulnerable, that is prone to rupture or erosion. Here, the ECM and tissue repair play an important role in plaque stability, vulnerability and progression. This review will focus on ECM remodelling in atherosclerotic plaques, with focus on how ECM biomarkers might predict plaque vulnerability and outcome.

Vulnerability to stress-induced inflammation has been linked to a dysfunctional hypothalamus–pituitary–adrenal (HPA) axis. In the present study, patients with known or suspected coronary artery disease (CAD) were assessed with respect to inflammatory and HPA axis response to acute physical exercise. An exercise stress test was combined with SPECT myocardial perfusion imaging. Plasma and saliva samples were collected before and 30 min after exercise. Interleukin (IL)-6 and adrenocorticotropic hormone (ACTH) were measured in plasma, while cortisol was measured in both plasma and saliva. In total, 124 patients were included of whom 29% had a prior history of CAD and/or a myocardial perfusion deficit. The levels of exercise intensity and duration were comparable in CAD and non-CAD patients. However, in CAD patients, IL-6 increased after exercise (p = 0.019) while no differences were seen in HPA axis variables. Conversely, patients without CAD exhibited increased levels of ACTH (p = 0.003) and cortisol (p = 0.004 in plasma, p = 0.006 in saliva), but no change in IL-6. We conclude that the IL-6 response to acute physical exercise is exaggerated in CAD patients and may be out of balance due to HPA axis hypoactivity. It remains to be further investigated whether this imbalance is a potential diagnostic and therapeutic target in CAD.