Carotid Plaque Composition and Prediction of Incident Atherosclerotic Cardiovascular Disease.

Background: Whether information on carotid plaque composition contributes to prediction of incident atherosclerotic cardiovascular disease (ASCVD) remains to be investigated. We determined the sex-specific added value of carotid plaque components for predicting incident ASCVD events, beyond traditional cardiovascular risk factors.

Methods: Between 2007 and 2012, participants from the population-based Rotterdam Study with asymptomatic carotid wall thickening >2.

Cardiac abnormalities in athletes after SARS-CoV-2 infection: a systematic review.

Objectives: Quantification of pericardial/myocardial involvement and risks of sudden cardiac arrest/sudden cardiac death (SCA/SCD) after SARS-CoV-2 infection in athletes who return to sports.

Design: Systematic review on post-SARS-CoV-2 infection pericardial/myocardial manifestations in athletes.

Data Sources: Combinations of key terms in Medline, Embase and Scopus (through 2 June 2021).

Return to sports after COVID-19: a position paper from the Dutch Sports Cardiology Section of the Netherlands Society of Cardiology.

The coronavirus disease 2019 (COVID-19) pandemic has led to preventive measures worldwide. With the decline of infection rates, less stringent restrictions for sports and exercise are being implemented. COVID-19 is associated with significant cardiovascular complications; however there are limited data on cardiovascular complications and long-term outcomes in both competitive (elite) athletes and highly active individuals.

Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

Reversal of Aging-Induced Increases in Aortic Stiffness by Targeting Cytoskeletal Protein-Protein Interfaces.

Background: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening.

Methods And Results: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome-wide association study of carotid-femoral pulse wave velocity.

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals.

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues.

International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.

Background: Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence.

Methods And Results: Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4-7 years), puberty (8-12 years), and postpuberty (13-20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5'-C-phosphate-G-3' methylation site) during prepuberty (P=2.

Association of renal function with vascular stiffness in older adults: the Rotterdam study.

Background: arterial stiffening is a marker of vascular ageing and an independent risk factor for cardiovascular disease. A potential mechanism linking cardiovascular disease to chronic kidney disease might be the change in arterial elasticity. We aim to determine the association between renal function and arterial stiffness in older subjects.

Adrenomedullin and arterial stiffness: integrative approach combining monocyte ADM expression, plasma MR-Pro-ADM, and genome-wide association study.

Background: Adrenomedullin (ADM) is a circulating vasoactive peptide involved in vascular homeostasis and endothelial function. Single nucleotide polymorphisms of the ADM gene are associated with blood pressure variability, and elevated levels of plasma midregional proadrenomedullin (MR-pro-ADM) are associated with cardiovascular diseases.

Methods And Results: We investigated the sources of variability of ADM gene expression and plasma MR-pro-ADM concentrations in the general population, and their relationship with markers of atherosclerosis.

Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations.

Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations.

Expression and gene variation studies deny association of human HSD3B1 gene with aldosterone production or blood pressure.

Background: Recent evidence suggests that the type I 3β-hydroxysteroid dehydrogenase, a steroidogenic enzyme encoded by the HSD3B1 gene, could be involved in aldosterone production and that genetic variation in HSD3B1 is associated with blood pressure. These findings challenge the long-standing hypothesis that all adrenocortical steroidogenesis is executed by the type II iso-enzyme, encoded by HSD3B2.

Methods: To verify these findings, the adrenal presence of HSD3B1 and its effect on aldosterone synthesis and blood pressure were studied in expression and genetic association analyses, respectively.

Arterial stiffness and hypertension in a large population of untreated individuals: the Rotterdam Study.

Objective: We studied whether arterial stiffness measured as aortic pulse wave velocity (aPWV) and carotid distensibility was associated with different subtypes of hypertension in a large population of untreated middle-aged and elderly men and women.

Methods: The study was conducted within the framework of the population-based Rotterdam Study. We included 4088 individuals with information on aPWV, with 3554 individuals with carotid distensibility measurements without use of antihypertensive medication.

Arterial stiffness is associated with carotid intraplaque hemorrhage in the general population: the Rotterdam study.

Objective: The relation between arterial stiffness and atherosclerosis, and specifically the influence of arterial stiffness on plaque composition, is largely unknown. In a population-based study, we investigated the association between arterial stiffness and the presence and composition of carotid atherosclerotic plaques.

Approach And Results: Arterial stiffness was measured in 6527 participants (67.

Overlap between common genetic polymorphisms underpinning kidney traits and cardiovascular disease phenotypes: the CKDGen consortium.

Background: Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits.

Study Design: We conducted 2 targeted analyses.

The impact of partial and complete loss-of-function mutations in endothelial lipase on high-density lipoprotein levels and functionality in humans.

Background: Endothelial lipase is a phospholipase with activity against high-density lipoprotein. Although a small number of mutations in LIPG have been described, the role of LIPG in protection against atherosclerosis is unclear.

Methods And Results: We identified 8 loss-of-function (LOF) mutations in LIPG in individuals with high-density lipoprotein cholesterol.

Blood pressure parameters and carotid intraplaque hemorrhage as measured by magnetic resonance imaging: The Rotterdam Study.

Intraplaque hemorrhage (IPH) is a characteristic of the vulnerable atherosclerotic plaque that has been associated with ischemic stroke. Not much is known about determinants of IPH. We studied whether blood pressure parameters are associated with presence of IPH.

Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study.

Background And Purpose: Aging and vascular risk factors contribute to arterial stiffening. Increased arterial stiffness exposes the small vessels in the brain to abnormal flow pulsations and, as such, may contribute to the pathogenesis of cerebral small vessel disease. In a population-based study, we investigated the association between arterial stiffness, as measured by aortic pulse wave velocity (aPWV), and small vessel disease.

Nucleotide excision DNA repair is associated with age-related vascular dysfunction.

Background: Vascular dysfunction in atherosclerosis and diabetes mellitus, as observed in the aging population of developed societies, is associated with vascular DNA damage and cell senescence. We hypothesized that cumulative DNA damage during aging contributes to vascular dysfunction.

Methods And Results: In mice with genomic instability resulting from the defective nucleotide excision repair genes ERCC1 and XPD (Ercc1(d/-) and Xpd(TTD) mice), we explored age-dependent vascular function compared with that in wild-type mice.

Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.

Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.

Methods And Results: A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.

Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study.

Background: Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear.

Objective: To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions.

Design: Prospective population-based study.

Genome-wide profiling of blood pressure in adults and children.

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms.