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• This is an analysis from HELLAS-FH registry. • 1655 adults with heterozygous FH (HeFH) were included. • Over half of HeFH adults have overweight or obesity. • Obesity was associated with increased prevalence of coronary artery disease. Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease [PAD]), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04–2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17–2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population. [Display omitted] [ABSTRACT FROM AUTHOR]

Leukocytosis, the expansion of white blood cells, is associated with increased cardiovascular risk. Studies in animal models have shown that high-density lipoprotein cholesterol (HDL-c) suppresses leukocytosis by mediating cholesterol efflux from hematopoietic stem and progenitor cells. HDL-c showed a moderate negative association with leukocyte numbers in the UK Biobank and Multi-Ethnic Study of Atherosclerosis. Cholesterol efflux capacity of HDL (HDL-CEC) or HDL particle (HDL-P) number has been proposed as improved inverse predictor of CVD compared to plasma HDL-c. In the LifeLines DEEP (LLD) cohort (n = 962), a sub-cohort representing the prospective population-based LL cohort from the North of The Netherlands, we tested the hypothesis that HDL-CEC and HDL-P were associated with lower leukocyte counts. We carried out multivariable regression and causal mediation analyses (CMA) to test associations between HDL-c, HDL-CEC, or HDL-P and leukocyte counts. We measured HDL-CEC in THP-1 macrophages and HDL-P and composition using nuclear magnetic resonance. HDL-c associated negatively with leukocyte counts, as did extra-large and large HDL-P, while HDL-CEC showed no association. Each one-standard deviation (SD) increase in extra-large HDL-P was associated with 3.0% and 4.8% lower leukocytes and neutrophils, respectively (q < 0.001). In contrast, plasma concentration of small HDL-P associated positively with leukocyte and neutrophil counts, as did small HDL-P triglycerides (TG) and total plasma TG. CMA showed that the association between S-HDL-P and leukocytes was mediated by S-HDL-TG. The association between HDL-P and leukocyte counts in the general population is dependent on HDL-P size and composition, but not HDL-CEC. [Display omitted] • High-density lipoprotein cholesterol (HDL-c) negatively associates with leukocyte counts independent of cholesterol efflux capacity of HDL (HDL-CEC). • Extra-large and large HDL particles (HDL-P) negatively associate with leukocyte counts. • The strong positive association between small HDL-P and leukocyte counts is mediated by HDL-triglycerides (TG). • S-HDL-TG showed a strong positive correlation with total plasma TG. [ABSTRACT FROM AUTHOR]

Background/Aim: The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption. Methods: Between 2002–2004, 1772 men and 1931 women aged 54–79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 − 5 g/d), low (> 5 to ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women, > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude. Results: Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[− 0.17(95%CI − 0.32; − 0.02)], and Bif-IMTmean[− 0.07(95%CI − 0.13; − 0.01)] at baseline and decreasing C-IMTmean[− 0.006 (95%CI − 0.011; − 0.000)], Bif-IMTmean[− 0.016(95%CI − 0.027; − 0.005)], ICA-IMTmean[− 0.009(95% − 0.016; − 0.002)] and ICA-IMTmax[− 0.016(95%: − 0.032; − 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT. Conclusion: In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders. [ABSTRACT FROM AUTHOR]

Background: To explore the role of large-artery atherosclerosis in migraine, we investigated the association between migraine and arterial calcification in different intracranial and extracranial vessels.Methods: 1856 participants were included, mean age (standard deviation) 67.4 (5.8) years, from the population-based Rotterdam Study cohort. Migraine was assessed by validated questionnaire and vascular calcification was assessed by computed tomography (expressed in Agatston score for the coronary arteries and volume in mm3 for the aortic arch, intracranial, and extracranial carotid arteries). Per vessel, the association of migraine with calcification was investigated by linear regression, adjusted for age, sex, cardiovascular risk factors, and calcification in other vessels.Results: Of the participants, 279 (15%) were identified as persons with lifetime migraine. In multivariable adjusted models, migraine was associated with smaller intracranial carotid artery calcification volume (difference in log-transformed calcification volume in persons with migraine compared to persons without migraine: -0.19[-0.29, -0.08]). While subjects with migraine also showed a lower calcification burden in the remaining arterial beds, those associations did not reach statistical significance.Conclusions: Persons with migraine, compared to those without, had less arterial calcification in the intracranial carotid artery, but not in other arterial beds. Future studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD), especially atherosclerotic cardiovascular disease (ASCVD), is one of the most important disease problems in the world accounting for an estimated 18.6 million deaths globally. Although older individuals are more often affected, ASCVD event at a young age is of particular importance because of more healthy years lost. Therefore, it is important to identify young individuals correctly at risk of ASCVD events in an early stage. Unfortunately, current risk score algorithms underestimate ASCVD event risk at a younger age. Both coronary artery calcium scoring (CACs) and family history of premature ASCVD (FH-PASCVD) have emerged as reliable screening tools to be able to identify individuals at risk for ASCVD events. Positive FH-PASCVD is associated with higher absolute CAC scores in first-degree 'healthy' family members and the proportion of individuals above the CACs percentile threshold to warrant treatment is also higher as compared to the general population. Therefore, a positive FH-PASCVD identifies so-called high-risk families and adding CAC scoring within these families identifies individuals at increased risk for ASCVD events. In individuals from high-risk families with an elevated CAC score, ASCVD events can be prevented when treated with statins and aspirin. Therefore, we suggest assessing FH-PASCVD in young 'healthy' individuals as a first screening step and subsequently performing CAC scoring to be able to start treatment at an early stage, since not only the lower is better, but also the earlier is better. [Display omitted] • The high recurrence rate of atherosclerotic cardiovascular disease among young individuals and even more important acute myocardial infarction in young women has increased tremendously over time. • Individuals with a family history of premature atherosclerotic cardiovascular disease, so-called high-risk families, might be at increased risk of atherosclerotic cardiovascular disease events and can best be identified by a coronary artery calcium score. • Asymptomatic individuals from high-risk families have higher coronary artery calcium scores than the general population and the increased risk for future atherosclerotic cardiovascular disease is dependent on coronary artery calcium score and not merely on having a positive family history of premature atherosclerotic cardiovascular disease. • Coronary artery calcium scoring in asymptomatic individuals from high-risk families will help in risk reclassification as every member from a high-risk family will not have the same risk of getting future atherosclerotic cardiovascular disease events. [ABSTRACT FROM AUTHOR]

Background: Carotid artery atherosclerosis is an important risk factor for stroke. As such, quantitative imaging of carotid artery calcification, as a proxy of atherosclerosis, has become a cornerstone of current stroke research. Yet, population-based data comparing the computed tomography (CT) and cardiovascular magnetic resonance (CMR) for the detection and quantification of calcification remain scarce. Methods: A total of 684 participants from the population-based Rotterdam Study underwent both a CT and CMR of the carotid artery bifurcation to quantify the amount of carotid artery calcification (mean interscan interval: 4.9 ± 1.2 years). We investigated the correlation between the amount of calcification measured on CT and CMR using Spearman's correlation coefficient, Bland-Altman plots, and linear regression. In addition, using logistic regression modeling, we assessed the association of CT and CMR based calcification volumes with a history of stroke. Results: We found a strong correlation between CT and CMR based calcification volumes (Spearman's correlation coefficient:0.86, p-value ≤0.01). Bland-Altman analyses showed a good agreement, though CT based calcification volumes were systematically larger. Finally, calcification volume assessed with either imaging modality was associated with a history of stroke with similar effect estimates (odds ratio (OR) per 1-SD increase in calcification volume: 1.52 (95% CI:1.00;2.30) for CT, and 1.47 (95% CI:1.01;2.14) for CMR. Conclusion: CT based and CMR based volumes of carotid artery calcification are highly correlated, but CMR based calcification is systematically smaller than those obtained with CT. Despite this difference, both provide comparable information with regard to a history of stroke. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the association between markers of atherosclerosis and the presence and progression of knee OA in a population-based cohort study. Methods. The study was performed within the framework of the prospective Rotterdam Study. Markers of atherosclerosis included coronary artery calcification (CAC) and plasma levels of CD40L, vascular cell adhesion molecule 1 (VCAM-1) and VEGF. CAC data were available for 1669 participants, and CD40L, VCAM-1 and VEGF data for 975. Radiographs of the knee were scored with the Kellgren and Lawrence score for OA at baseline and follow-up [average follow-up time 4.5 years (S.D. 0.5)]. We used multivariate logistic regression models with generalized estimated equations to calculate odds ratios (95% CIs) for the association of atherosclerosis markers with prevalence and progression of knee OA. Results. The mean age was 73.1 (S.D. 7.5) years. Within the study population, 18% had radiographic knee OA (11% of men and 23% of women). CAC and VEGF were not associated with prevalent knee OA. Only among women, CD40L [adjusted odds ratio 1.3 (1.1, 1.6)] and VCAM-1 [adjusted odds ratio 1.3 (1.1, 1.6)] were associated with prevalent knee OA. No associations with progression were found in women. In men, too few progressors were available to assess associations. Conclusion. In this population-based study, CAC and VEGF were not associated with the presence or progression of knee OA. Only among women, plasma levels of CD40L and VCAM-1 were higher in individuals with knee OA compared with those without knee OA. This might suggest an association between atherosclerosis and knee OA through low-grade systemic inflammation in women. [ABSTRACT FROM AUTHOR]

Objective. The incidence of cardiovascular disease (CVD) is increased in RA. This study was designed to evaluate whether a reduction in disease activity influences early markers of CVD. Methods. In a prospective longitudinal study, 58 newly diagnosed RA patients and 58 age- and sex-matched healthy controls (HCs) were included. Endothelial dysfunction was measured by small artery elasticity (SAE) and endothelial cell activation was assessed by measuring soluble vascular cellular activation molecule 1(sVCAM-1) and von Willebrand factor (vWF). Advanced glycation end products (AGEs) were quantified by skin autofluorescence. After 1 year, measurements were repeated in all RA patients. Results. At entry, SAE was decreased in RA vs HCs [median 3.4 ml/mmHg100 (range 1.2–9.0) vs 6.1 (range 5.0–15.3), P < 0.0001] and sVCAM-1 and vWF were increased: 391 ng/ml (range 256–680) vs 341 (range 223–691) (P = 0.0015) and 120 ng/ml (range 26.5–342) vs 99 (range 22–298) (P = 0.02), respectively. SAE was inversely correlated with the 28-joint DAS (DAS28; r = −0.31, P = 0.016). AGEs were increased by 2.55 arbitrary units (range 1.29–4.65) vs 2.12 (range 1.32–3.82) in HCs (P = 0.003). In multivariate analysis, the presence of RA, age and systolic blood pressure were independently and inversely related to SAE. After 1 year, SAE had significantly improved in RA, from 3.4 (range 1.2–9.0) to 3.8 (range 1.5–10.3) (P = 0.03). Conclusion. Endothelial dysfunction is present in newly diagnosed RA patients, independently of traditional risk factors and is inversely correlated with disease activity. By reducing disease activity, endothelial dysfunction improves, although not to normal values. Also, a reduction in disease activity targeting traditional risk factors remains important in preventing CVD in RA. [ABSTRACT FROM AUTHOR]

Objectives. The aims of this study were to investigate (i) associations between uric acid and prevalent cardiovascular disease (CVD), ankle–arm blood pressure index (AAIx) and carotid intima–media thickness (CIMT) in the total population and in predefined subgroups according to glucose metabolism status and (ii) the extent to which these associations are explained by low-grade inflammation.Methods. Cross-sectional analyses were conducted among 530 individuals [60.6% men, mean age 58.9 years (s.d. 6.9), 52.6% normal glucose metabolism (NGM)] at increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht study. A low-grade inflammation score was computed by averaging the z-scores of eight inflammation markers [CRP, TNF-α, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin].Results. After adjustment for traditional CVD risk factors, plasma uric acid (per s.d. of 81 μmol/l) was associated with CVD in individuals with NGM [odds ratio (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM) (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated with CIMT in the total population (β = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (β = 0.030, 95% CI 0.006, 0.054) than DGM (β = 0.018, 95% CI −0.009, 0.044, P interaction = 0.443). There was no association between uric acid and AAIx in any group (P interaction = 0.058). Uric acid was associated with low-grade inflammation in the total population (β = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low-grade inflammation to the models did not attenuate any of the associations.Conclusion. The associations for uric acid with CIMT, and with CVD in NGM only, were not explained by low-grade inflammation. A difference in the strength of the associations between individuals with NGM and DGM was suggested. [ABSTRACT FROM PUBLISHER]

Aim Systematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and Methods Literature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials, including also a non-intervention group. Data were extracted and meta-analyses were performed. Results From 3928 screened studies, 25 trials met the eligibility criteria. These trials enrolled 1748 periodontitis patients. Seven trials enrolled periodontitis patients that were otherwise healthy, 18 trials recruited periodontal patients with various co-morbidities, such as CVD or diabetes. None of the trials used hard clinical endpoints of CVD. However, improvement of endothelial function has been consistently reported. Meta-analyses demonstrated significant weighted mean difference (WMD) for hsCRP (−0.50 mg/l, 95% CI:−0.78; −0.22), IL-6 (−0.48 ng/l, 95% CI: −0.90; −0.06), TNF-α (−0.75 pg/ml, 95% CI: −1.34; −0.17), fibrinogen (−0.47 g/l, 95% CI: −0.76; −0.17), total cholesterol (−0.11 mmol/l, 95% CI: −0.21; −0.01) and HDL-C (0.04 mmol/l, 95% CI: 0.03; 0.06) favouring periodontal intervention. Importantly, periodontitis patients with co-morbidity benefitted most from periodontal therapy; significant WMD were observed for levels of hsCRP (−0.71 mg/l, 95% CI: −1.05; −0.36), IL-6 (−0.87 ng/l, 95% CI: −0.97; −0.78), triglycerides (−0.24 mmol/l, 95% CI: −0.26; −0.22), total cholesterol (−0.15 mmol/l, 95% CI: −0.29; −0.01), HDL-C (0.05 mmol/l, 95% CI: 0.03; 0.06) and HbA1c (−0.43%, 95% CI: −0.60; −0.25). Conclusions This systematic review and meta-analyses demonstrate that periodontal treatment improves endothelial function and reduces biomarkers of atherosclerotic disease, especially in those already suffering from CVD and/or diabetes. [ABSTRACT FROM AUTHOR]

Background: Screening with ankle-brachial index (ABI) measurement could be clinically relevant to avoid cardiovascular events in subjects with asymptomatic atherosclerosis. To assess the practical impact of guidelines regarding the use of ABI as a screening tool in general practice, the corresponding number needed to screen, including the required time investment, and the feasibility of ABI performance, was assessed. Methods: An observational study was performed in the setting of 955 general practices in the Netherlands. Overall, 13,038 subjects of ≥55 years presenting with symptoms of intermittent claudication and/or presenting with ? one vascular risk factor were included. Several guidelines recommend the ABI as an additional measurement in selected populations for risk assessment for cardiovascular morbidity. Results: Screening of the overall population of ?50 years results in862 subjects per general practice who should be screened, resulting in a time-requirement of approximately 6 weeks of full time work. Using an existing clinical prediction model, 247 patients per general practice should be screened for PAD by ABI measurement. Conclusion: Screening the entire population of ?50 years will in our opinion not be feasible in general practice. A more rationale and efficient approach might be screening of subsets of the population of ?55 years based on a clinical prediction model. [ABSTRACT FROM AUTHOR]

BackgroundDepression increases the risk of subsequent vascular events in both cardiac and non-cardiac patients. Atherosclerosis, the underlying process leading to vascular events, has been associated with depression. This association, however, may be confounded by the somatic-affective symptoms being a consequence of cardiovascular disease. While taking into account the differentiation between somatic-affective and cognitive-affective symptoms of depression, we examined the association between depression and atherosclerosis in a community-based sample.MethodIn 1261 participants of the Nijmegen Biomedical Study (NBS), aged 50–70 years and free of stroke and dementia, we measured the intima–media thickness (IMT) of the carotid artery as a measure of atherosclerosis and we assessed depressive symptoms using the Beck Depression Inventory (BDI). Principal components analysis (PCA) of the BDI items yielded two factors, representing a cognitive-affective and a somatic-affective symptom cluster. While correcting for confounders, we used separate multiple regression analyses to test the BDI sum score and both depression symptom clusters.ResultsWe found a significant correlation between the BDI sum score and the IMT. Cognitive-affective, but not somatic-affective, symptoms were also associated with the IMT. When we stratified for coronary artery disease (CAD), the somatic-affective symptom cluster correlated significantly with depression in both patients with and patients without CAD.ConclusionsThe association between depressive symptoms and atherosclerosis is explained by the somatic-affective symptom cluster of depression. Subclinical vascular disease thus may inflate depressive symptom scores and may explain why treatment of depression in cardiac patients hardly affects vascular outcome. [ABSTRACT FROM PUBLISHER]

Background: Observational studies have shown that low folate and elevated homocysteine concentrations are risk factors for vascular disease in the general population. Randomized controlled trials in vascular patients have failed to show that folic acid reduces the risk of recurrent vascular disease, whereas such trials are lacking in the general population. Objective: The objective was to determine whether folic acid supplementation reduces the progression of atherosclerosis as measured by common carotid intima-media thickness (CIMT)-a validated marker of atherosclerosis and predictor of vascular disease risk. Design: A randomized, double-blind, placebo-controlled study in 819 men and postmenopausal women aged 50-70 y, free-living in the Netherlands, and with a total homocysteine concentration ≥13 μmol/L at screening was conducted. Participants received either 800 μg folic acid or placebo daily for 3 y. Rate of change in CIMT and arterial distensibility were the primary and secondary outcomes, respectively. Results: Compared with placebo, serum folate increased by 577% and plasma total homocysteine concentrations decreased by 26% after 3 y of folic acid supplementation. The mean (±SE) rate of change in CIMT was 1.9 ± 0.9 μm/y in the folic acid arm and 1.3 ± 0.8 μm/y in the placebo arm (mean difference: 0.7 μm/y; 95% CI: -1.8, 3.1 μm/y; P = 0.59). No difference was observed (P = 0.23) between the rates of change in distensibility in the folic acid arm (-0.53 ± 0.06 x 10-3 kPa-1) and in the placebo arm (-0.62 ± 0.06 x 10-3 kPa-1). Conclusion: Despite a considerable increase in folate concentrations and a reduction in total homocysteine concentrations, 3-y folic acid supplementation did not slow down atherosclerotic progression or arterial stiffening. This trial was registered at clinicaltrials.gov as NCT00110604 [ABSTRACT FROM AUTHOR]

Abstract: Objective: The use of the HIV-protease inhibitor ritonavir (RTV) is associated with induction of hypertriglyceridemia, which is a cardiovascular risk factor. Therefore, we investigated the effect of RTV on atherosclerosis development in APOE*3-Leiden transgenic mice, a model for human-like lipoprotein metabolism and atherosclerosis. Methods and results: APOE*3-Leiden mice were fed a Western-type diet without or with RTV (35mg/kg/day) for 19 weeks. RTV increased plasma TG levels throughout the study (∼2-fold; P <0.05). Despite these increased TG levels, RTV decreased the atherosclerotic lesion area in the aortic root (−57%; P <0.05), concomitant with reduced macrophage area (−72%; P <0.01) and decreased lesion severity. This could not be explained by reduced inflammatory markers in plasma (i.e. serum amyloid A, E-selectin and fibrinogen), nor by decreased lipid accumulation in macrophages or increased cholesterol efflux from macrophages, as assessed using peritoneal macrophages in vitro. Rather, whereas RTV did not affect plasma total cholesterol levels, RTV decreased (V)LDL-cholesterol and increased cholesterol in apoE-rich large HDL. Conclusion: Despite inducing hypertriglyceridemia, RTV decreases atherosclerotic lesion area and severity, associated with decreased (V)LDL-cholesterol and increased atheroprotective apoE-rich large HDL. [Copyright &y& Elsevier]

Objectives: High-density lipoprotein (HDL) cholesterol elevation is associated with an improved outcome in patients with atherosclerotic disease. Niaspan®, a prolonged-release nicotinic acid, was evaluated during the Niaspan-Induced HDL Elevation for Optimizing Risk Control (NEMO) study in The Netherlands. Methods: NEMO was a 6-month, prospective, observational, multicentre, open-label study. Niaspan was prescribed in statin-treated patients with known or suspected atherosclerotic disease. The main outcome measures were treatment-related adverse drug reactions (ADRs) and effects on lipids and cardiovascular-risk score based on the algorithm derived from the Prospective Cardiovascular Münster study. Results: 612 patients were included in The Netherlands. Flushing was the most common ADR (29% of patients during the first month of treatment). The main reasons for treatment discontinuation were flushing (10.5%), patient request (8.0%) and being lost to follow-up (6.0%). About half of all patients (52%) continued treatment after the study. Tolerability was rated ‘good’ or ‘very good’ in 54% of these patients. HDL cholesterol increased by 23% from baseline, and triglycerides were reduced by 16%, with little change in low-density lipoprotein or total cholesterol. Cardiovascular risk score was reduced by 3.3 points. Conclusions: The use of the prolonged-release nicotinic acid Niaspan in patients with or at risk for atherosclerotic disease showed good tolerability, a marked increase in HDL cholesterol and a reduced cardiovascular risk score. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Measurement of the ankle-brachial index (ABI) can provide important information about the presence of subclinical atherosclerosis. Performing the ABI in the overall population is not feasible, but it can be used in a selected population. A simple prediction rule could be of much use to estimate the risk of an abnormal ABI. This was designed as an observational study in the setting of 955 general practices in The Netherlands. A total of 7454 patients aged ≥55 years presenting with at least one vascular risk factor (smoking, hypertension, diabetes, and hypercholesterolemia) and no complaints of intermittent claudication were included. Patients were selected by the general practitioner during visiting hours and from medical records. Main outcome measures included the prevalence of PAD, defined as an ABI below 0.9, which was related to vascular risk factors using regression analyses on which the PREVALENT clinical prediction model was developed. The overall prevalence of PAD was 18.4%. Since the treatment of individuals with a history of coronary heart disease and cerebrovascular disease will not be influenced by the finding of asymptomatic PAD, these individuals were not taken into account for the development of the clinical prediction model. Analyses showed a significantly increased risk for PAD with increasing age, smoking, and hypertension. The clinical prediction model giving risk factor points per factor (age: 1 point per 5 years starting at 55 years; ever smoked: 2 points; currently smoking: 7 points; and hypertension: 3 points), showed a proportional increase of the PAD prevalence with each increasing risk profile (range: 7.0–40.6%). In conclusion, based on the PREVALENT clinical prediction model, the general practitioner is able to identify a high-risk population in which measurement of ABI is useful. [ABSTRACT FROM AUTHOR]

Background: Patients with hypertension may be vulnerable to vascular Chlamydia pneumoniae and/or cytomegalovirus (CMV) infection because of increased expression of adhesion molecules. Objective: To determine whether C pneumoniae or CMV is associated with the presence of atherosclerotic lesions in hypertensive patients. Methods: Ninety-six angiographic studies on 100 consecutive patients with of clinical signs or symptoms suggestive of renovascular hypertension were reviewed for the presence or absence of atherosclerotic lesions at the level of the renal arteries as well and abdominal aorta. Also, the presence of a hemodynamically notable renal artery stenosis and antibodies to C pneumoniae (IgG and IgA) and CMV (IgG and IgM) was determined, and all classic risk factors were recorded. Results: Atherosclerotic lesions were documented in 67 patients (70%), and in 49 patients (51%) such lesions were persent at the level of the renal artery. In the univariate analysis, significant associations between IgG (odds ratio, 3.8; 95% confidence interval, 1.2-11.7; P = .02) as well as IgA (odds ratio, 2.6; 95% confidence interval, 1.1-6.7; P = .03) antibodies to C pneumoniae and the presence of atherosclerosis were found for both the aorta and the renal arteries. Seroprevalence (IgG) to C pneumoniae in the 23 patients with a hemodynamically notable renal artery stenosis was 100% and differed (P = .01) from those without a notable renal artery stenosis (78%). In the multivariate analysis, IgG seropositivity to C pneumoniae was significantly associated with atherosclerosis (odds ratio, 6.0; 95% confidence interval, 1.33-27.5; P = .02), and age. There was no association between CMV seropositivity and atherosclerosis. Conclusion: The presence of antibodies to C pneumoniae was significantly associated with atherosclerosis and renovascular disease in hypertensive patients in whom a renal artery stenosis was strongly suspected. [ABSTRACT FROM AUTHOR]

The current study describes the age- and sex-specific incidence rates and risk factors for asymptomatic and symptomatic peripheral arterial occlusive disease (PAOD) among 2,327 subjects and the incidence of intermittent claudication in asymptomatic PAOD subjects. The study population was selected from 18 general practice centers in the Netherlands. PAOD was assessed with the ankle-brachial blood pressure index, and intermittent claudication was assessed with a modified version of the Rose questionnaire. After 7.2 years, the overall incidence rate for asymptomatic PAOD, using the person-years method, was 9.9 (95% confidence interval (CI): 7.3, 18.8) per 1,000 person-years at risk. The rate was 7.8 (95% CI: 4.9, 20.3) for men and 12.4 (95% CI: 7.7, 24.8) for women. For symptomatic PAOD, the incidence rate was 1.0 (95% CI: 0.7, 7.5) overall, 0.4 (95% CI: 0.3, 10.0) for men, and 1.8 (95% CI: 1.0, 10.3) for women. Multivariate analyses showed that increasing age, smoking, hypertension, and diabetes mellitus were the most important risk factors. The overall incidence rate for intermittent claudication among PAOD subjects who were asymptomatic at baseline was 90.5 per 1,000 person-years at risk (95% CI: 36.4, 378.3). The incidence of asymptomatic PAOD was higher than the incidence of symptomatic PAOD, with women developing PAOD more often than men. In the development of preventive strategies, modification of atherosclerotic risk factors, such as smoking, hypertension, and diabetes, should be the main goals. Am J Epidemiol 2001;153:666-72. [ABSTRACT FROM AUTHOR]

Rationale: Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context., Methods and Results: In patients with chronic kidney disease, plasma OMD levels correlated with markers of inflammation and bone turnover, with the protein present in calcified arterial media. Plasma OMD also associated with cardiac calcification and the protein was detected in calcified valve leaflets by immunohistochemistry. In patients with carotid atherosclerosis, circulating OMD was increased in association with plaque calcification as assessed by computed tomography. Transcriptomic and proteomic data showed that OMD was upregulated in atherosclerotic compared to control arteries, particularly in calcified plaques, where OMD expression correlated positively with markers of smooth muscle cells (SMCs), osteoblasts and glycoproteins. Immunostaining confirmed that OMD was abundantly present in calcified plaques, localised to extracellular matrix and regions rich in α-SMA + cells. In vivo, OMD was enriched in SMCs around calcified nodules in aortic media of nephrectomised rats and in plaques from ApoE -/- mice on warfarin. In vitro experiments revealed that OMD mRNA was upregulated in SMCs stimulated with IFNγ, BMP2, TGFβ1, phosphate and β-glycerophosphate, and by administration of recombinant human OMD protein (rhOMD). Mechanistically, addition of rhOMD repressed the calcification process of SMCs treated with phosphate by maintaining their contractile phenotype along with enriched matrix organisation, thereby attenuating SMC osteoblastic transformation. Mechanistically, the role of OMD is exerted likely through its link with SMAD3 and TGFB1 signalling, and interplay with BMP2 in vascular tissues., Conclusion: We report a consistent association of both circulating and tissue OMD levels with cardiovascular calcification, highlighting the potential of OMD as a clinical biomarker. OMD was localised in medial and intimal α-SMA + regions of calcified cardiovascular tissues, induced by pro-inflammatory and pro-osteogenic stimuli, while the presence of OMD in extracellular environment attenuated SMC calcification., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Objective: Mast cells (MCs) are important contributors to atherosclerotic plaque progression. For prospective studies on mast cell contributions to plaque instability, the distribution of intraplaque MCs needs to be elucidated. Plaque stability is generally histologically assessed by dividing the plaque specimen into segments to be scored on an ordinal scale. However, owing to competitive use, studies may have to deviate to adjacent segments, yet intersegment differences of plaque characteristics, especially MCs, are largely unknown. Therefore, the hypothesis that there is no segment to segment difference in MC distribution between atherosclerotic plaque segments was tested, and intersegment associations between MCs and other plaque characteristics was investigated., Methods: Twenty-six carotid atherosclerotic plaques from patients undergoing carotid endarterectomy included in the Athero-Express Biobank were analysed. The plaque was divided in 5 mm segments, differentiating between the culprit lesion (segment 0), adjacent segments (-1/+1) and more distant segments (-2/+2) for the presence of MCs. The associations between the intersegment distribution of MCs and smooth muscle cells, macrophage content, and microvessel density in the culprit lesion were studied., Results: A statistically significant difference in MCs/mm 2 between the different plaque segments (p < .001) was found, with a median of 2.79 (interquartile range [IQR] 1.63 - 7.10) for the culprit lesion, 1.34 (IQR 0.26 - 4.45) for the adjacent segment, and 0.62 (0.14 - 2.07) for the more distant segment. Post hoc analyses showed that intersegment differences were due to differences in MCs/mm 2 between the culprit and adjacent segment (p = .037) and between the culprit lesion and the more distant segment (p < .001). MCs/mm 2 in multiple different segments were positively correlated with microvessel density and macrophage content in the culprit lesion., Conclusion: MC numbers reveal significant intersegment differences in human carotid plaques. Future histological studies on MCs should use a standardised segment for plaque characterisation as plaque segments cannot be used interchangeably for histological MC analyses., (Copyright © 2021. Published by Elsevier B.V.)

Background: Microcalcifications cannot be identified with the present resolution of CT; however, 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) imaging has been proposed for non-invasive identification of microcalcification. The primary objective of this study was to assess whether 18 F-NaF activity can assess the presence and predict the progression of CT detectable vascular calcification., Methods and Results: The data of two longitudinal studies in which patients received a 18 F-NaF PET-CT at baseline and after 6 months or 1-year follow-up were used. The target to background ratio (TBR) was measured on PET at baseline and CT calcification was quantified in the femoral arteries at baseline and follow-up. 128 patients were included. A higher TBR at baseline was associated with higher calcification mass at baseline and calcification progression (β = 1.006 [1.005-1.007] and β = 1.002 [1.002-1.003] in the studies with 6 months and 1-year follow-up, respectively). In areas without calcification at baseline and where calcification developed at follow-up, the TBR was .11-.13 (P < .001) higher compared to areas where no calcification developed., Conclusion: The activity of 18 F-NaF is related to the amount of calcification and calcification progression. In areas where calcification formation occurred, the TBR was slightly but significantly higher., (© 2020. The Author(s).)

Objective: Bicuspid aortic valve (BAV) has been associated with less atherosclerosis as compared with tricuspid aortic valve (TAV) patients. It, however, remains unclear whether this reflects the older age of TAV patients and/or accumulation of atherosclerotic risk factors or that the BAV phenotype is atheroprotective. Therefore, we compared the atherosclerotic disease burden of BAV and TAV patients, with that of the general (age-matched) population., Methods: The prevalence of coronary artery disease (CAD) and CAD risk factors in BAV and TAV patients who underwent aortic valve surgery were compared with the Dutch general practitioners registry data. BAV (n=454) and TAV (n=1101) patients were divided into four groups: BAV with aortic valve stenosis (BAV-AoS), BAV with aortic valve regurgitation (BAV-AR), TAV with AoS (TAV-AoS) and TAV with AR (TAV-AR). The atherosclerotic disease burden of each group was compared with that of the corresponding age cohort for the general population., Results: CAD risk factors hypertension and hypercholesterolaemia were more prevalent in the surgery groups than the age-matched general population (all p<0.001). All BAVs (BAV-AoS and BAV-AR) and TAV-AR had a similar incidence of CAD history as compared to the age-matched general populations (p=0.689, p=0.325 and p=0.617 respectively), whereas TAV-AoS had a higher incidence (21.6% versus 14.9% in the age-matched general population, p<0.001)., Conclusions: Stenotic TAV disease is part of the atherosclerotic disease spectrum, while regurgitant TAV and all BAVs are not. Although the prevalence of cardiovascular risk factors is higher in all BAV patients, the prevalence of CAD is similar to the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We investigated the role of blood pressure, vessel wall stiffness [pulse wave velocity (PWV)] and subclinical atherosclerosis markers [carotid intima-media thickness (cIMT), popliteal vessel wall thickness (pVWT)] as mediators of the association of obesity with OA., Methods: We used cross-sectional data from a subset of the population-based NEO study (n = 6334). We classified clinical hand and knee OA by the ACR criteria, and structural knee OA, effusion and bone marrow lesions on MRI (n = 1285). cIMT was assessed with ultrasonography. pVWT was estimated on knee MRI (n = 1285), and PWV by abdominal velocity-encoded MRIs (n = 2580), in subpopulations. Associations between BMI and OA were assessed with logistic regression analyses, adjusted for age, sex and education. Blood pressure, cIMT, pVWT and PWV were added to the model to estimate mediation., Results: The population consisted of 55% women, with a mean (s.d.) age of 56(6) years. Clinical hand OA was present in 8%, clinical knee OA in 10%, and structural knee OA in 12% of participants. BMI was positively associated with all OA outcomes. cIMT partially mediated the association of BMI with clinical hand OA [10.6 (6.2; 30.5)%], structural knee OA [3.1 (1.9; 7.3)%] and effusion [10.8 (6.0; 37.6)%]. Diastolic blood pressure [2.1 (1.6; 3.0)%] minimally mediated the association between BMI and clinical knee OA. PWV and pVWT did not mediate the association between BMI and OA., Conclusions: cIMT and diastolic blood pressure minimally mediated the association of BMI with OA. This suggests that such mediation is trivial in the middle-aged population., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background The aim of this study was to investigate whether increased severity of coronary artery calcium (CAC), an imaging biomarker of subclinical coronary atherosclerosis, is associated with worse cognitive function independent of cardiovascular risk factors in a large population-based Dutch cohort with broad age range. Methods and Results A cross-sectional analysis was performed in 4988 ImaLife participants (aged 45-91 years, 58.3% women) without history of cardiovascular disease. CAC scores were obtained using nonenhanced cardiac computed tomography scanning. The CogState Brief Battery was used to assess 4 cognitive domains: processing speed, attention, working memory, and visual learning based on detection task, identification task, 1-back task, and 1-card-learning task, respectively. Differences in mean scores of each cognitive domain were compared among 4 CAC categories (0, 1-99, 100-399, ≥400) using analysis of covariates to adjust for classical cardiovascular risk factors. Age-stratified analysis (45-54, 55-64, and ≥65 years) was performed to assess whether the association of CAC severity with cognitive function differed by age. Overall, higher CAC was associated with worse performance on 1-back task after adjusting for classical cardiovascular risk factors, but CAC was not associated with the other cognitive tasks. Age-stratified analyses revealed that the association of CAC severity with working memory persisted in participants aged 45 to 54 years, while in the elderly this association lost significance. Conclusions In this Dutch population of ≥45 years, increased CAC severity was associated with worse performance of working memory, independent of classical cardiovascular risk factors. The inverse relationship of CAC score categories with working memory was strongest in participants aged 45 to 54 years.

Turner syndrome (TS) is associated with coronary artery disease (CAD), an important cause of premature death in TS. However, the determinants of CAD in women with TS remain unknown. In a cross-sectional study design, 168 women without clinical evidence of CAD (115 with TS and 53 without TS) were assessed for the presence and volume of subclinical CAD using coronary CT angiography. Karyotype, the presence of congenital heart defects and conventional cardiovascular risk factors were also registered. Comparative analyses were performed (1) between women with and without TS and (2) in the TS group, between women with and without subclinical CAD. The prevalence of CAD, in crude and adjusted analyses, was not increased for women with TS (crude prevalence: 40 [35%] in TS vs. 25 [47%] in controls, p = 0.12). The volume of atherosclerosis was not higher in women with TS compared with controls (median and interquartile range 0 [0-92] in TS vs. 0 [0-81]mm 3 in controls, p = 0.29). Among women with TS, women with subclinical CAD were older (46 ± 13 vs. 37 ± 11 years, p < 0.001), had higher blood pressure (systolic blood pressure 129 ± 16 vs. 121 ± 16 mmHg, p < 0.05) and were more frequently diagnosed with type 2 diabetes (5 [13%] vs. 2 [3%], p < 0.05). Karyotype or congenital heart defects were not associated with subclinical CAD. Some women with TS show early signs of CAD, however overall, not more than women without TS. Conventional cardiovascular risk factors were the principal determinants of CAD also in TS, and CAD prevention strategies should be observed.ClinicalTrial.gov Identifier: NCT01678261 ( https://clinicaltrials.gov/ct2/show/NCT01678261 ).

Background: Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated., Methods: We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies., Results: Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5-12.2] versus odds ratio, 1.2 [95% CI, 0.6-2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8-8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia., Conclusions: Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531.

Background and Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n = 3673) of men (47.9%) and women (52.1%)., Methods: Individuals (aged 54-79 years) free of CV diseases were enrolled in seven centers of five European countries: Finland, France, Italy, the Netherlands, and Sweden. PCSK9 plasma levels were measured by ELISA., Results: PCSK9 was higher in women than in men. Multiple linear regression analysis showed that latitude, sex, and treatments with statins and fibrates were the strongest predictors of PCSK9 in the whole group. These variables, together with triglycerides and high-density lipoprotein cholesterol, were also associated with PCSK9 in men or women. Mean corpuscular hemoglobin concentration and pack-years were PCSK9 independent predictors in women, whereas hypercholesterolemia and physical activity were independent predictors in men. The associations between PCSK9 and latitude, uric acid, diabetes, hypercholesterolemia and physical activity were significantly different in men and women (p interaction <0.05 for all)., Conclusions: Besides confirming the association with lipids in the whole group, our study revealed previously unknown differences in PCSK9 predictors in men and women. These might be taken into account when defining individual risk for CV events and/or for refining PCSK9 lowering treatments., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Context: Not all obese individuals develop cardiovascular disease (CVD). Hyperaldosteronism is suggested to cause inflammation and metabolic dysregulation, and might contribute to CVD development in obese individuals., Objective: We aimed to investigate the association of aldosterone concentrations with inflammation, metabolic disturbances, and atherosclerosis in overweight and obese individuals. Additionally, we measured renin concentrations to investigate whether the observed effects reflected general activation of the renin-angiotensin-aldosterone system (RAAS)., Design: A cross-sectional cohort study (300-OB study) was conducted. Various inflammatory parameters, traits of the metabolic syndrome, lipidome and metabolome parameters, fat distribution, and carotid atherosclerosis were associated with plasma aldosterone and renin levels., Setting: The setting of this study was the Radboudumc (i.o. Radboudumc), the Netherlands., Patients: A total of 302 individuals with a body mass index greater than or equal to 27 kg/m2 participated., Main Outcome Measures and Results: Aldosterone was associated with various markers of inflammation and metabolic dysregulation, which partly differed from the associations observed for renin. Although both were associated with inflammatory cell numbers, only renin was associated with classical markers of systemic inflammation. Both were associated with the metabolic syndrome and hepatic steatosis. Of the traits that constitute metabolic syndrome, aldosterone, but not renin, was associated with triglyceride concentrations. Accordingly, aldosterone was associated with large very low-density lipoprotein particles; metabolomics studies further associated aldosterone with urate concentrations and derivatives of the linoleic acid metabolism pathway. Neither aldosterone nor renin was associated with atherosclerotic plaque thickness., Conclusions: Aldosterone is not an important driver of systemic inflammation in the obese, whereas aldosterone concentrations and metabolic dysregulation are strongly intertwined in these individuals. Although prospective studies are necessary to validate these results, the independent effects of aldosterone on carotid atherosclerosis appear modest., (© Endocrine Society 2020.)

Purpose: The aim of this study was to study temporal changes in metabolite profiles in patients with post-acute coronary syndrome (ACS), in particular prior to the development of recurrent ACS (reACS). Methods: BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective study including patients admitted for ACS, who underwent high-frequency blood sampling during 1-year follow-up. Within BIOMArCS, we performed a nested case-cohort analysis of 158 patients (28 cases of reACS). We determined 151 metabolites by nuclear magnetic resonance in seven (median) blood samples per patient. Temporal evolution of the metabolites and their relation with reACS was assessed by joint modelling. Results are reported as adjusted (for clinical factors) hazard ratios (aHRs). Results: Median age was 64 (25th-75th percentiles; 56-72) years and 78% were men. After multiple testing correction ( p  < 0.001), high concentrations of extremely large very low density lipoprotein (VLDL) particles (aHR 1.60/SD increase; 95%CI 1.25-2.08), very large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25-2.08) and large VLDL particles (aHR 1.56/SD increase; 95%CI 1.22-2.05) were significantly associated with reACS. Moreover, these longitudinal particle concentrations showed a steady increase over time prior to reACS. Among the other metabolites, no significant associations were observed. Conclusion: Post-ACS patients with persistent high concentrations of extremely large, very large and large VLDL particles have increased risk of reACS within 1 year.

Context: Primary aldosteronism (PA) confers an increased risk of cardiovascular disease (CVD), independent of blood pressure. Animal models have shown that aldosterone accelerates atherosclerosis through proinflammatory changes in innate immune cells; human data are scarce., Objective: The objective of this article is to explore whether patients with PA have increased arterial wall inflammation, systemic inflammation, and reprogramming of monocytes., Design: A cross-sectional cohort study compared vascular inflammation on 2'-deoxy-2'-(18F)fluoro-D-glucose; (18F-FDG) positron emission tomography-computed tomography, systemic inflammation, and monocyte phenotypes and transcriptome between PA patients and controls., Setting: This study took place at Radboudumc and Rijnstate Hospital, the Netherlands., Patients: Fifteen patients with PA and 15 age-, sex-, and blood pressure-matched controls with essential hypertension (EHT) participated., Main Outcome Measures and Results: PA patients displayed a higher arterial 18F-FDG uptake in the descending and abdominal aorta (P < .01, P < .05) and carotid and iliac arteries (both P < .01). In addition, bone marrow uptake was higher in PA patients (P < .05). Although PA patients had a higher monocyte-to-lymphocyte ratio (P < .05), systemic inflammatory markers, cytokine production capacity, and transcriptome of circulating monocytes did not differ. Monocyte-derived macrophages from PA patients expressed more TNFA; monocyte-derived macrophages of healthy donors cultured in PA serum displayed increased interleukin-6 and tumor necrosis factor-α production., Conclusions: Because increased arterial wall inflammation is associated with accelerated atherogenesis and unstable plaques, this might importantly contribute to the increased CVD risk in PA patients. We did not observe inflammatory reprogramming of circulating monocytes. However, subtle inflammatory changes are present in the peripheral blood cell composition and monocyte transcriptome of PA patients, and in their monocyte-derived macrophages. Most likely, arterial inflammation in PA requires interaction between various cell types., (© Endocrine Society 2019.)

Objective: Sudden cardiac death (SCD) in families with premature atherosclerosis (PAS) is generally attributed to lethal arrhythmias during myocardial infarction. Yet, such arrhythmias may also arise from non-ischaemic inherited susceptibility. We aimed to test the hypothesis that Brugada syndrome is prevalent among families with PAS in which SCD occurred., Methods: We investigated all patients who underwent Ajmaline testing to screen them for Brugada syndrome because of unexplained familial SCD in the Amsterdam University Medical Centers between 2004 and 2017. We divided the cohort into two groups based on a positive family history for PAS. All individuals with a positive Ajmaline test were screened for SCN5A-mutation., Results: In families with SCD and PAS, the prevalence of positive Ajmaline test was similar to families with SCD alone (22% vs 19%). The number of SCD cases in families with SCD and PAS was higher (2.34 vs 1.63, p<0.001) and SCD occurred at older age in families with SCD and PAS (42 years vs 36 years, p<0.001), while the prevalence of SCN5A mutations was lower (3% vs 18%, p<0.05)., Conclusions: Brugada syndrome has a similar prevalence in families with SCD and PAS as in families with SCD alone, although SCD in families with SCD and PAS occurs in more family members and at older age, while SCN5A mutations in these families are rare. This suggests that the SCD occurring in families with PAS could be related to an underlying genetic predisposition of arrhythmias, with a different genetic origin. It could be considered to screen families with SCD and PAS for Brugada syndrome., Competing Interests: Competing interests: All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly higher patency rates for covered stents (CS). The Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI) trial is designed to prospectively assess the patency of CS versus BMS in patients with atherosclerotic CMI., Methods/design: The CoBaGI trial is a randomized controlled, parallel-group, patient- and investigator-blinded, superiority, multicenter trial conducted in six centers of the Dutch Mesenteric Ischemia Study group (DMIS). Eighty-four patients with a consensus diagnosis of atherosclerotic CMI are 1:1 randomized to either a balloon-expandable BMS (Palmaz Blue with rapid-exchange delivery system, Cordis Corporation, Bridgewater, NJ, USA) or a balloon-expandable CS (Advanta V12 over-the-wire, Atrium Maquet Getinge Group, Hudson, NH, USA). The primary endpoint is the primary stent-patency rate at 24 months assessed with CT angiography. Secondary endpoints are primary stent patency at 6 and 12 months and secondary patency rates, freedom from restenosis, freedom from symptom recurrence, freedom from re-intervention, quality of life according the EQ-5D-5 L and SF-36 and cost-effectiveness at 6, 12 and 24 months., Discussion: The CoBaGI trial is designed to assess the patency rates of CS versus BMS in patients treated for CMI caused by atherosclerotic mesenteric stenosis. Furthermore, the CoBaGI trial should provide insights in the quality of life of these patients before and after stenting and its cost-effectiveness. The CoBaGI trial is the first randomized controlled trial performed in CMI caused by atherosclerotic mesenteric artery stenosis., Trial Registration: ClinicalTrials.gov, ID: NCT02428582 . Registered on 29 April 2015.

Background and Aims: Arteriosclerosis in the vertebrobasilar arteries may play an important role in the etiology of posterior circulation strokes, but little is known on its prevalence, its correlation with arteriosclerosis in other major arteries, and its risk factors. Hence, we investigated these aspects of vertebrobasilar artery calcification (VBAC) as marker of vertebrobasilar arteriosclerosis., Methods: To quantify VBAC, 2483 participants (mean age: 69.2 years, 52% female) from the Rotterdam Study underwent non-enhanced computed tomography. We determined the presence and volume of VBAC. Next, using Spearman's rank correlation, we examined the correlation between the volume of VBAC and the volume of coronary artery calcification (CAC), aortic arch calcification (AAC), and both extracranial- (ECAC), and intracranial carotid artery calcification (ICAC). Finally, we investigated associations of cardiovascular risk factors with the presence and volume of VBAC using logistic and linear regression models., Results: The overall prevalence of VBAC was 21.0% (median volume: 7.3 mm 3 [IQR: 2.0-25.6]). Correlations between VBAC and CAC, AAC, ECAC, and ICAC were weak to moderate (men: 0.33, 0.28, 0.30, 0.36; women: 0.26, 0.24, 0.24, 0.35, respectively). Hypertension, diabetes, and current smoking were associated with the presence of VBAC in both sexes (men: OR 1.67 [95%-CI, 1.14-2.46], 1.60 [95%-CI, 1.10-2.34], 1.48 [95%-CI, 1.02-2.14]; women: OR 1.51 [95%-CI, 1.01-2.26], 1.56 [95%-CI, 1.02-2.39], 1.53 [95%CI, 1.00-2.33], respectively). In men, obesity was also associated with VBAC (1.42 [95%-CI, 1.00-2.02])., Conclusions: VBAC occurs in over 20% of elderly community dwelling persons. Cardiovascular risk factors are associated with VBAC with similar patterns for men and women., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Inflammation may underlie the association between obesity, atherosclerosis and cardiovascular disease. We investigated to what extent markers of inflammation mediate associations between overall and visceral body fat and subclinical atherosclerosis., Methods and Results: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study we estimated total body fat (TBF) by bio-impedance analysis, carotid artery intima media thickness (cIMT) by ultrasound, C-reactive protein (hs-CRP) and glycoprotein acetyls (GlycA) concentrations in fasting blood samples (n = 5627), and visceral adipose tissue (VAT) by magnetic resonance imaging (n = 2247). We examined associations between TBF and VAT, and cIMT using linear regression, adjusted for potential confounding factors, and for mediators: cardiometabolic risk factors (blood pressure, glucose and low-density lipoprotein cholesterol), and inflammation using CRP and GlycA as proxies. Mean (SD) cIMT was 615 (90) μm. Per SD of TBF (8%), cIMT was 19 μm larger (95% confidence interval, CI: 10, 28). This association was 17 μm (95% CI: 8, 27) after adjustment for cardiometabolic risk factors, and did not change after adjustment for markers of inflammation. Per SD (56 cm 2 ) VAT, cIMT was 9 μm larger (95% CI: 2, 16) which changed to 5 μm (95% CI: -3, 12) after adjustment for cardiometabolic risk factors, and did not change after adjustment for inflammatory markers., Conclusion: Our results suggest that associations between measures of overall and visceral body fat and subclinical atherosclerosis are not mediated by inflammation as measured by CRP and GlycA. Obesity may exert cardiovascular risk via other markers of systemic inflammation., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Rationale: Altered gut microbial composition has been linked to cardiovascular diseases (CVDs), but its functional links to host metabolism and immunity in relation to CVD development remain unclear., Objectives: To systematically assess functional links between the microbiome and the plasma metabolome, cardiometabolic phenotypes, and CVD risk and to identify diet-microbe-metabolism-immune interactions in well-documented cohorts., Methods and Results: We assessed metagenomics-based microbial associations between 231 plasma metabolites and microbial species and pathways in the population-based LLD (Lifelines DEEP) cohort (n=978) and a clinical obesity cohort (n=297). After correcting for age, sex, and body mass index, the gut microbiome could explain ≤11.1% and 16.4% of the variation in plasma metabolites in the population-based and obesity cohorts, respectively. Obese-specific microbial associations were found for lipid compositions in the VLDL, IDL, and LDL lipoprotein subclasses. Bacterial L-methionine biosynthesis and a Ruminococcus species were associated to cardiovascular phenotypes in obese individuals, namely atherosclerosis and liver fat content, respectively. Integration of microbiome-diet-inflammation analysis in relation to metabolic risk score of CVD in the population cohort revealed 48 microbial pathways associated to CVD risk that were largely independent of diet and inflammation. Our data also showed that plasma levels rather than fecal levels of short-chain fatty acids were relevant to inflammation and CVD risk., Conclusions: This study presents the largest metagenome-based association study on plasma metabolism and microbiome relevance to diet, inflammation, CVD risk, and cardiometabolic phenotypes in both population-based and clinical obesity cohorts. Our findings identified novel bacterial species and pathways that associated to specific lipoprotein subclasses and revealed functional links between the gut microbiome and host health that provide a basis for developing microbiome-targeted therapy for disease prevention and treatment.

Background The purpose of this study was to investigate the association between kidney function and arterial calcification in major vascular beds and to establish whether arterial calcification mediates the relation between kidney function measures and cardiovascular disease ( CVD ) incidence. Methods and Results In 2241 participants from the Rotterdam Study (mean age 69 years, 52% female), kidney function was assessed using the estimated glomerular filtration rate and urine albumin-to-creatinine ratio. All participants underwent noncontrast computed tomography to quantify the amount of arterial calcification in the coronary arteries, aortic arch, extracranial, and intracranial internal carotid arteries. We used linear regression models, adjusted for age, sex, and cardiovascular risk factors, to evaluate the association between kidney function and arterial calcification volume in the 4 vessel beds. Incidence rate of CVD was calculated in 3 groups of participants based on their kidney function and presence of arterial calcification. We conducted mediation analysis to evaluate whether arterial calcification mediates this association. We found that in age- and sex-adjusted models, lower estimated glomerular filtration rate and higher albumin-to-creatinine ratio were associated with larger calcification volumes in all 4 vascular beds. Adjusting for cardiovascular risk factors attenuated the effect estimates. CVD incidence was higher in participants with estimated glomerular filtration rate <60 mL/min per 1.73 m 2 and presence of arterial calcification compared with individuals with estimated glomerular filtration rate >60 and no calcification. After adjusting for cardiovascular risk factors, arterial calcification did not mediate the association between kidney function measures and CVD incidence. Conclusions The association of impaired kidney function and larger volumes of arterial calcification is partly explained by cardiovascular risk factors. Arterial calcification does not mediate the association between kidney function and CVD beyond cardiovascular risk factors.

Background Several trials to prevent cardiovascular disease by inhibiting cholesteryl ester transfer protein (CETP) have failed, except Randomized EValuation of the Effects of Anacetrapib through Lipid-modification. Thus far, it is unclear to what extent CETP is causally related to measures of atherosclerosis. Objective The aim of the article was to study the causal relationship between genetically determined CETP concentration and carotid intima-media thickness (cIMT) in a population-based cohort study. Methods In the Netherlands Epidemiology of Obesity study, participants were genotyped, and cIMT was measured by ultrasonography. We examined the relation between a weighted genetic risk score for CETP concentration, based on 3 single-nucleotide polymorphisms that have previously been shown to largely determine CETP concentration and cIMT using Mendelian randomization in the total population and in strata by sex, Framingham 10-year risk, (pre)diabetes, high-density lipoprotein cholesterol, triglycerides, and statin use. Results We analyzed 5655 participants (56% women) with a mean age of 56 (range 44–66) years, body mass index of 26 (range 17–61) kg/m 2 , and serum CETP of 2.47 (range 0.68–5.33) μg/mL. There was no evidence for a causal relation between genetically determined CETP and cIMT in the total population, but associations were differently directed in men (16 μm per μg/mL increase in genetically determined CETP; 95% confidence interval: −8, 39) and women (−8 μm; −25, 9). Genetically determined CETP appeared to be associated with cIMT in normoglycemic men (26 μm; −1, 52) and in (pre)diabetic women (48 μm; −2, 98). Conclusion In this population-based study, there was no causal relation between genetically determined CETP concentration and cIMT in the total population although we observed directionally differing effects in men and women. Stratified results suggested associations in individuals with different cardiometabolic risk factor profiles, which require replication. [ABSTRACT FROM AUTHOR]

Background People are in a postprandial state for the majority of the day, postprandial triglyceride (TG) response may be more important in the etiology of atherosclerosis than fasting TGs. Objective The objective of the study was to investigate the associations of fasting TG concentration (TGc) and postprandial TG response after a meal challenge with subclinical atherosclerosis, measured by intima-media thickness (IMT) in a middle-aged population. Methods A total of 5574 participants (57% women) with a mean (standard deviation [SD]) age of 56 (6) years were included in this cross-sectional analysis of baseline measurements of The Netherlands Epidemiology of Obesity study. Serum TGc was measured fasting and 30 and 150 minutes after a liquid mixed meal, and the incremental area under the curve (TGiAUC) was calculated. With linear regression analyses, we calculated the differences in IMT with 95% confidence intervals, adjusted for confounding factors, and additionally for TGc or TGiAUC. Results Per SD of TGc (0.82 mmol/L), IMT was 8.5 μm (2.1, 14.9) greater after adjustment for TGiAUC and confounding factors. Per SD of TGiAUC (24.0 mmol/L × min), the difference in IMT was −1.7 μm (−8.5, 5.0) after adjustment for fasting TG and confounding factors. Conclusions The association between TG response after a mixed meal and IMT disappeared after adjusting for TGc. The association between fasting TG concentration and IMT persisted after adjustment for postprandial TG response. These findings imply that it is not useful to perform a meal challenge in cardiovascular risk stratification. Our results support use of fasting TGc instead of postprandial TG responses for cardiovascular risk stratification in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Lecithin:cholesterol acyltransferase (LCAT) is the sole enzyme that esterifies cholesterol in plasma. Its role in the supposed protection from atherogenesis remains unclear because mutations in LCAT causing fish-eye disease (FED) or familial LCAT deficiency (FLD) have been reported to be associated with more or instead less carotid atherosclerosis, respectively. This discrepancy may be associated with the loss of cholesterol esterification on only apolipoprotein AI (FED) or on both apolipoprotein AI- and apolipoprotein B-containing lipoproteins (FLD), an aspect that has thus far not been investigated., Methods: Seventy-four heterozygotes for LCAT mutations recruited from Italy and the Netherlands were assigned to FLD (n=33) or FED (n=41) groups and compared with 280 control subjects. Subclinical atherosclerosis was assessed with carotid intima-media thickness., Results: Compared with control subjects, total cholesterol was lower by 16% (-32.9 mg/dL) and 7% (-14.9 mg/dL) and high-density lipoprotein cholesterol was lower by 29% (-16.7 mg/dL) and 36% (-20.7 mg/dL) in the FLD and FED groups, respectively. Subjects with FLD displayed a significant 18% lower low-density lipoprotein cholesterol compared with subjects with FED (101.9±35.0 versus 123.6±47.4 mg/dL; P=0.047) and control subjects (122.6±35.0 mg/dL; P=0.003). Remarkably, all 3 intima-media thickness parameters were lower in subjects with FLD compared with FED and control subjects (accounting for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids). After additional correction for nationality and ultrasonographic methods, average and maximum intima-media thickness remained significantly lower when subjects with FLD were compared with those with FED (0.59 versus 0.73 mm, P=0.003; and 0.87 versus 1.24 mm, P<0.001, respectively). In contrast, the common carotid intima-media thickness (corrected for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids) was higher in subjects with FED compared with control subjects (0.69 versus 0.65 mm; P=0.05), but this significance was lost after adjustment for nationality and ultrasonographic machine., Conclusions: In this head-to-head comparison, FLD and FED mutations were shown to be associated with decreased and increased atherosclerosis, respectively. We propose that this discrepancy is related to the capacity of LCAT to generate cholesterol esters on apolipoprotein B-containing lipoproteins. Although this capacity is lost in FLD, it is unaffected in FED. These results are important when considering LCAT as a target to decrease atherosclerosis.

Background and Aims: Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification., Methods: Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis., Results: In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27-3.44]) and hypertension (OR 2.09 [CI 1.29-3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11-5.14]) and previous vascular disease (OR 2.20 [CI 1.30-3.75])., Conclusions: Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Carotid arterial diameter enlargement is a manifestation of arterial remodeling and may be a risk factor for cardiovascular disease (CVD). We evaluated the association between carotid artery diameter and risk of stroke, coronary heart disease, CVD, and all-cause mortality and explored whether the associations could be explained by processes involved in arterial remodeling, that is, blood pressure-related media thickening, arterial stiffness, arterial wall stress, and atherosclerosis. We included 4887 participants (mean age 67±9 years; 54% women) from 4 cohort studies: Rotterdam Study, NEPHROTEST, Hoorn Study, and a study by Blacher et al. Common carotid artery properties were measured using echotracking. Incident cases were recorded based on medical records. We used Cox proportional hazard models adjusting for cardiovascular risk factors and estimates of processes underlying arterial remodeling. During follow-up (mean, 11 years), 379 (8%) individuals had a stroke, 516 had a (11%) coronary heart disease, 807 had a (17%) CVD, and 1486 (30%) had died. After adjustment for cardiovascular risk factors, individuals in the highest tertile of carotid diameter (diameter >8 mm) compared with those in the lowest tertile (diameter <7 mm) had a higher incidence of stroke (hazard ratio, 1.5; 95% confidence interval, 1.1-2.0). From all estimates of processes underlying arterial remodeling, adjustment for carotid intima-media thickness attenuated this association (hazard ratio after adjustment for intima-media thickness, 1.2; 95% confidence interval, 0.9-1.6). Larger carotid diameter was associated with risk of CVD and mortality but not clearly with coronary heart disease risk. We showed that a larger carotid diameter is associated with incident stroke, CVD, and mortality. Carotid intima-media thickness, a measure of blood pressure-related media thickening, partially explained the association with stroke incidence., (© 2018 American Heart Association, Inc.)

Background and Aims: In patients with impaired renal function and macroalbuminuria, cardiovascular risk factors are highly prevalent, however, whether this is also present in the general population is unclear. We investigated whether normal-range albuminuria and renal function are associated with cardiovascular function in the general population., Methods: In this cross-sectional analysis of the NEO study, urinary albumin-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and intima-media thickness were assessed in all participants (n = 6503), and a random subset underwent MRI for pulse wave velocity (n = 2451) and/or cardiac imaging (n = 1138)., Results: Multiple linear regression analysis was performed while adjusting for sex, age, smoking, mean arterial blood pressure, total body fat, and fasting glucose. After adjustment, albuminuria and renal function were positively associated with left ventricle (LV) mass index (UACR, 0.941 g/m 2 [95% CI: 0.21,1.67] p = 0.012; eGFR, 0.748 g/m 2 [95% CI: 0.15,1.35] p = 0.015) and LV cardiac index (UACR, 0.056 L/min/m 2 [95% CI: 0.00,0.11] p = 0.038; eGFR, 0.080 L/min/m 2 [95% CI: 0.03,0.13] p = 0.001). Albuminuria showed a weak association with arterial thickness (UACR, 0.003 mm [95% CI: 0.00,0.01] p = 0.015) and arterial stiffness (UACR, 0.073 m/s [95% CI: 0.01,0.13] p = 0.036), but not with renal function. No associations were observed for LV ejection fraction and LV diastolic function., Conclusions: Normal-range albuminuria was positively associated with LV mass index, LV cardiac index, arterial thickness and arterial stiffness. Our findings support the hypothesis that even within normal range, albuminuria is a marker of cardiovascular health., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Rheumatoid arthritis (RA) has been associated with an increased risk of atherosclerosis. We aimed to evaluate the progression of carotid intima media thickness (cIMT) in RA patients subject to a cardiovascular treat-to-target intervention. In addition, the presence of the metabolic syndrome (MetS) on cIMT outcomes was evaluated., Methods: We performed a cohort analysis of FRANCIS, in which RA patients ≤70 years without CVD or diabetes mellitus were randomized for either a treat-to-target intervention or usual care concerning CVD risk factors. MetS was scored at baseline., Results: Three-year data was available in 212 well-controlled RA patients. The treat-to-target intervention resulted in a lower cIMT progression over three years compared to the usual care. However, there was no difference in cIMT at three years between groups. MetS was present in 40.1% of RA patients. Baseline cIMT was significantly higher in RA patients with MetS compared to those without (0.619 (0.112) versus 0.557 (0.104) mm; p < 0.001). After three years, cIMT progression was comparable (0.043 (0.071) versus 0.043 (0.072) mm; p = 0.96). In RA patients with MetS, the presence of plaques increased over three years from 12.9% to 23.5% (p = 0.01). The type of intervention had no effect on cIMT progression in RA patients with MetS. However, in subjects without MetS, treat-to-target resulted in a lower progression., Conclusions: RA patients with MetS showed an increased CVD risk profile based on both a higher prevalence of CVD risk factors and structural vascular changes. A treat-to-target approach of CVD risk factors reduced cIMT progression only in RA patients without MetS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge., Methods and Results: We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d 6 -choline and d 3 -carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18 F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells., Conclusions: Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation., Clinical Trial Registration: URL: http://www.trialregister.nl. Unique identifier: NTR 4338., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)