Genetics of Subclinical Coronary Atherosclerosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Bielak LF
PROVIDER: S-EPMC6405218 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Genetics of Subclinical Coronary Atherosclerosis.
Bielak Lawrence F LF Peyser Patricia A PA
Current genetic medicine reports 20180713 3
<h4>Purpose of review</h4>This review highlights recent findings regarding genetics of coronary artery calcification (CAC), a marker of subclinical atherosclerosis burden, that is a precursor of clinical coronary artery disease.<h4>Recent findings</h4>CAC quantity is heritable. Genome wide association studies of common single nucleotide polymorphisms have identified genomic regions explaining ~2.4% of CAC heritability. Low frequency and rare variants explain additional variation in CAC. Evidence ...[more]
Similar Datasets
Project description:ObjectiveWhether HIV modifies the relationship of serum lipids with coronary atherosclerosis and coronary plaque subtypes is uncertain. We examined the associations between traditional lipids and coronary atherosclerosis among HIV-infected (HIV+) and HIV-uninfected (HIV-) men.DesignThe Multicenter AIDS Cohort Study is an observational cohort with a total of 429 HIV+ and 303 HIV- men who had non-contrast cardiac computed tomography performed to measure coronary artery calcium and coronary computed tomography angiography to measure coronary stenosis, coronary plaque presence, and composition.MethodsWe used multivariable adjusted prevalence ratios to examine the relationship between the SD difference in each lipid parameter and coronary atherosclerosis.ResultsTotal cholesterol (TC)/HDL-cholesterol had the strongest associations with coronary atherosclerosis regardless of HIV status. Overall, lipid parameters were most strongly associated with the presence of mixed plaque, stenosis more than 50%, and coronary artery calcium for both HIV+ and HIV- men. HIV+ men had similar, but weaker associations, between lipid parameters and coronary atherosclerosis compared with HIV- men. The strongest association was between the TC/HDL-cholesterol and stenosis more than 50% for both HIV+ [prevalence ratios 1.25 per SD (95% confidence interval 1.07-1.43)] and HIV- men [prevalence ratios 1.46 per SD (95% confidence interval 1.08-1.85)].ConclusionThe associations between lipids and coronary atherosclerosis tended to be weaker for HIV+ compared with HIV- men, although TC/HDL had the strongest association for both HIV+ and HIV- men. A weaker association between lipid levels and coronary atherosclerosis for HIV+ men may contribute to the decreased discrimination of cardiovascular disease risk observed in HIV+ individuals.
| S-EPMC6457132 | biostudies-literature
Project description:HIV infection is associated with increased prevalence of subclinical coronary plaque. The extent to which such plaque reflects effects of HIV infection or effects of long-term antiretroviral therapy (ART) use remains unclear and was the goal of this analysis.We compared the prevalence and extent of coronary plaque and stenosis between users of specific ART drugs or drug classes using coronary computed tomography (CT) among HIV-infected men in the Multicenter AIDS Cohort Study. To account for time-dependent confounders, including cardiovascular disease risk factors and time-varying reasons for using specific treatments, we conducted fully adjusted logistic and linear models with inverse probability of treatment weighting.There were 618 men who underwent noncontrast coronary CT; 450 also underwent coronary CT angiography. At the time of scanning, 81% had undetectable plasma HIV RNA. In fully adjusted models, cumulative use of zidovudine, abacavir, darunavir, and protease inhibitors as a drug class were inconsistently associated with specific forms of plaque presence or extent.Among virally suppressed HIV-infected men with extensive ART exposure, no consistent associations between use of specific ART drugs and both subclinical coronary plaque presence and extent were apparent. Our findings support the hypothesis that, among virally suppressed persons, type of ART used is not in general a major determinant of subclinical coronary plaque risk.
| S-EPMC5173385 | biostudies-literature
Project description:Background Data are limited on the association between marital status and subclinical coronary atherosclerosis. This study investigated the influence of marital status on subclinical coronary atherosclerosis detected by coronary computed tomographic angiography in an asymptomatic population. Methods and Results This retrospective study analyzed 9288 asymptomatic individuals (mean age, 53.7±8.0 years; 6041 [65%] men) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography during a general health examination. Marital categories were married (n=8481) versus unmarried (n=807), comprising never married (n=195), divorced (n=183), separated (n=119), and widowed (n=310) individuals. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography; ≥50% diameter stenosis was defined as significant. Logistic regression and propensity score matching analyses were used to determine the association between marital status and subclinical coronary atherosclerosis. After adjustment for cardiovascular risk factors, no significant differences were observed in the adjusted odds ratio (OR) of unmarried status for any coronary plaque (OR, 1.077; 95% CI, 0.899-1.291), calcified plaque (OR, 1.058; 95% CI, 0.881-1.271), noncalcified plaque (OR, 0.966; 95% CI, 0.691-1.351), mixed plaque (OR, 1.301; 95% CI, 0.884-1.917), and significant coronary artery stenosis (OR, 1.066; 95% CI, 0.771-1.474). Similarly, in the 2:1 propensity-score matched population (n=2398), no statistically significant differences were observed for the OR of marital status for any subclinical coronary atherosclerosis (P>0.05 for all). Conclusions In this large cross-sectional study, marital status was not associated with an increased risk of subclinical coronary atherosclerosis.
| S-EPMC9238701 | biostudies-literature
Project description:ObjectiveWhile the risk of acute coronary events has been associated with biological variability of circulating cholesterol, the association with variability of other atherogenic lipids remains less understood. We evaluated the longitudinal variability of 284 lipids and investigated their association with asymptomatic coronary atherosclerosis. Approach and Results: Circulating lipids were extracted from fasting blood samples of 83 community-sampled symptom-free participants (age 41-75 years), collected longitudinally over 6 months. Three types of coronary plaque volume (calcified, lipid-rich, and fibrotic) were quantified using computed tomography coronary angiogram. We first deconvoluted between-subject (CVg) and within-subject (CVw) lipid variabilities. We then tested whether the mean lipid abundance was different across groups categorized by Framingham risk score and plaques phenotypes (lipid-rich, fibrotic, and calcified). Finally, we investigated whether visit-to-visit variability of each lipid was associated with plaque burden. Most lipids (72.5%) exhibited higher CVg than CVw. Among the lipids (n=145) with 1.2-fold higher CVg than CVw, 26 species including glycerides and ceramides were significantly associated with Framingham risk score and the 3 plaque phenotypes (false discovery rate <0.05). In an exploratory analysis of person-specific visit-to-visit variability without multiple testing correction, high variability of 3 lysophospholipids (lysophosphatidylethanolamines 16:0, 18:0, and lysophosphatidylcholine O-18:1) was associated with lipid-rich and fibrotic (noncalcified) plaque volume while high variability of diacylglycerol 18:1_20:0, triacylglycerols 52:2, 52:3, and 52:4, ceramide d18:0/20:0, dihexosylceramide d18:1/16:0, and sphingomyelin 36:3 was associated with calcified plaque volume.ConclusionsHigh person-specific longitudinal variation of specific nonsterol lipids is associated with the burden of subclinical coronary atherosclerosis. Larger studies are needed to confirm these exploratory findings.
| S-EPMC8691371 | biostudies-literature
Project description:BackgroundEarly detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.MethodsWe recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.ResultsIn total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.ConclusionsUsing CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
| S-EPMC8448414 | biostudies-literature
Project description:Obesity is a common public health problem and obese individuals in particular have a disproportionate incidence of acute coronary events. This study was undertaken to identify coronary artery lesions as well as associated clinical features, risk factors and demographics in patients with a body mass index (BMI) >40 kg/m(2) without known coronary artery disease (CAD). Morbidly obese subjects were prospectively recruited to undergo coronary computed tomographic angiography (CCTA) using a dual-source computed tomography (CT) system. CAD was defined as the presence of any atherosclerotic lesion in any one coronary artery segment. The presence, location, and severity of atherosclerosis were related to patient characteristics. Forty-one patients (28 women, mean age, 50.4±10.0 years, mean BMI, 43.8±4.8 kg/m(2)) served as the study population. Of these, 25 patients (61%) had at least one coronary stenosis. All but 2 patients within the CAD cohort had coronary artery calcium (CAC) scores >0, and most plaques identified (75.4%) were non-calcified. There was a predilection of calcified and non-calcified atherosclerosis involving the left anterior descending (LAD) coronary artery compared with other coronary segments. Univariate predictors of CAD included older age, dyslipidemia, and diabetes. In this preliminary study of young morbidly obese patients, CCTA detected a high prevalence of calcified and non-calcified CAD, although the later predominated.
| S-EPMC3184688 | biostudies-literature
Project description:BACKGROUND AND AIMS:Frailty and cardiovascular disease share many risk factors. We evaluated whether frailty is independently associated with subclinical coronary atherosclerosis and whether any relationships differ by HIV-serostatus. METHODS:We studied 976 [62% HIV-infected] male participants of the Multicenter AIDS Cohort Study who underwent assessment of frailty and non-contrast cardiac CT scanning; of these, 747 men also underwent coronary CT angiography (CCTA). Frailty was defined as having ?3 of 5 of the following: weakness, slowness, weight loss, exhaustion, and low physical activity. Coronary artery calcium (CAC) was assessed by non-contrast CT, and total plaque score (TPS), mixed plaque score (MPS), and non-calcified plaque score (NCPS) by CCTA. Multivariable-adjusted regression was used to assess the cross-sectional associations between frailty and subclinical coronary atherosclerosis. RESULTS:Mean (SD) age of participants was 54 (7) years; 31% were black. Frailty existed in 7.5% and 14.3% of HIV-uninfected and HIV-infected men, respectively. After adjustment for demographics, frailty was significantly associated with prevalence of any CAC (CAC>0), any plaque (TPS>0), and mixed plaque (MPS>0) in HIV-uninfected but not in HIV-infected men (p-interactionHIV<0.05 for all). Among HIV-uninfected men, after adjustment for cardiovascular risk factors, frailty was significantly associated only with CAC>0 [Prevalence Ratio 1.27 (95%CI 1.02, 1.59)] and TPS>0 [1.19 (1.06, 1.35)]. No association was found for NCPS. CONCLUSIONS:Frailty was independently associated with subclinical coronary atherosclerosis among HIV-uninfected men, but not among HIV-infected men. Further work is needed to ascertain mechanisms underlying these differences and whether interventions that improve frailty (i.e. strength training) can improve cardiovascular outcomes.
| S-EPMC5671901 | biostudies-literature
Project description:BackgroundRecent genome-wide association studies have identified 49 single nucleotide polymorphisms associated with clinical coronary artery disease. The mechanism by which these loci influence risk remains largely unclear.Methods and resultsWe examined the association between a genetic risk score composed of high-risk alleles at the 49 single nucleotide polymorphisms and the degree of subclinical coronary atherosclerosis in 7798 participants from 6 studies stratified into 4 age groups at the time of assessment (15-34, 35-54, 55-74, and >75 years). Atherosclerosis was quantified by staining and direct visual inspection of the right coronary artery in the youngest group and by scanning for coronary artery calcification in the remaining groups. We defined cases as subjects within the top quartile of degree of atherosclerosis in 3 groups and as subjects with a coronary artery calcium score >0 in the fourth (35-54 years) where less than one quarter had any coronary artery calcium. In our meta-analysis of all strata, we found 1-SD increase in the genetic risk score increased the risk of advanced subclinical coronary atherosclerosis by 36% (P=8.3×10(-25)). This increase in risk was significant in all 4 age groups including the youngest group where atherosclerosis consisted primarily of raised lesions without macroscopic evidence of plaque rupture or thrombosis. Results were similar when we restricted the genetic risk score to 32 single nucleotide polymorphisms not associated with traditional risk factors or when we adjusted for traditional risk factors.ConclusionsA genetic risk score for clinical coronary artery disease is associated with advanced subclinical coronary atherosclerosis throughout the life-course. This association is apparent even at the earliest, uncomplicated stages of atherosclerosis.
| S-EPMC4824193 | biostudies-literature
Project description:Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. The development of coronary artery calcium scoring (CAC) and CT coronary angiography (CCTA) provide complementary tools to directly visualize coronary plaque and other risk-modifying imaging components that can potentially provide individualized lipid management. Understanding patient selection for CAC or potentially CCTA and the risk implications of the different parameters provided, such as CAC score, coronary stenosis, plaque characteristics and burden, epicardial adipose tissue, and pericoronary adipose tissue, have grown more complex as technologies evolve. These parameters directly affect the shared decision with patients to start or withhold lipid-lowering therapies, to adjust statin intensity or LDL cholesterol goals. Emerging lipid lowering studies with non-invasive imaging as a guide to patient selection and treatment efficacy, plus the evolution of lipid lowering therapies from statins to a diverse armament of newer high-cost agents have pushed these two fields forward with a complex interaction. This review will discuss existing risk estimators, and non-invasive imaging techniques for subclinical coronary atherosclerosis, traditionally studied using CAC and more recently CCTA with qualitative and quantitative measurements. We will also explore the current data, gaps of knowledge and future directions on the use of these techniques in the risk-stratification and guidance of lipid management.
| S-EPMC9813535 | biostudies-literature
Project description:BACKGROUND:Homocysteine has been known as a risk factor for cardiovascular disease. This study sought to evaluate the influence of homocysteine on the risk of subclinical coronary atherosclerosis in asymptomatic individuals. METHODS:We reviewed 3,186 asymptomatic individuals (mean age 53.8 ± 8.0 years, 2,202 men [69.1%]) with no prior history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography (CCTA) and laboratory tests as part of a general health examination. The subjects were stratified into tertiles according to their homocysteine levels. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA. Logistic regression analysis was used to determine the association between homocysteine levels and subclinical coronary atherosclerosis. RESULTS:The prevalence of significant coronary artery stenosis, any atherosclerotic, calcified, mixed, and non-calcified plaques increased with homocysteine tertiles (all p < 0.05). However, after adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios (ORs) for any atherosclerotic plaque (OR 1.06; 95% CI [confidence interval] 0.85-1.32; p = 0.610), calcified plaques (OR 1.17; 95% CI 0.92-1.48; p = 0.199), non-calcified plaques (OR 0.80; 95% CI 0.61-1.04; p = 0.089), and mixed plaques (OR 1.42; 95% CI 0.96-2.11; p = 0.077) between the third and first homocysteine tertiles. In addition, the adjusted OR for significant coronary artery stenosis (OR 0.92; 95% CI 0.63-1.36; p = 0.687) did not differ between the first and third tertiles. CONCLUSIONS:In asymptomatic individuals, homocysteine is not associated with an increased risk of subclinical coronary atherosclerosis.
| S-EPMC7141661 | biostudies-literature