scholarly journals Polygenic Hyperlipidemias and Coronary Artery Disease Risk

2020 ◽  
Vol 13 (2) ◽  
Author(s):  
Pietari Ripatti ◽  
Joel T. Rämö ◽  
Nina J. Mars ◽  
Yu Fu ◽  
Jake Lin ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Odds Ratio ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Risk Scores ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

Background: Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk. Methods: We derived polygenic risk scores (PRSs) with ≈6M variants separately for LDL-C and TG with weights from a UK Biobank–based genome-wide association study with ≈324K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the National FINRISK Study (FINRISK) cohort and to CAD risk in 135 638 individuals (13 753 CAD cases) from the FinnGen project (FinnGen). Results: In FINRISK, median LDL-C was 3.39 (95% CI, 3.38–3.40) mmol/L, and it ranged from 2.87 (95% CI, 2.82–2.94) to 3.78 (95% CI, 3.71–3.83) mmol/L between the lowest and highest 5% of the LDL-C PRS distribution. Median TG was 1.19 (95% CI, 1.18–1.20) mmol/L, ranging from 0.97 (95% CI, 0.94–1.00) to 1.55 (95% CI, 1.48–1.61) mmol/L with the TG PRS. In FinnGen, comparing the highest 5% of the PRS to the lowest 95%, CAD odds ratio was 1.36 (95% CI, 1.24–1.49) for the LDL-C PRS and 1.31 (95% CI, 1.19–1.43) for the TG PRS. These estimates were only slightly attenuated when adjusting for a CAD PRS (odds ratio, 1.26 [95% CI, 1.16–1.38] for LDL-C and 1.24 [95% CI, 1.13–1.36] for TG PRS). Conclusions: The CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and partially overlapping with a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing additional guidance for clinical translation.

scholarly journals Polygenic Hyperlipidemias and Coronary Artery Disease Risk

2019 ◽  
Author(s):  
Pietari Ripatti ◽  
Joel T Rämö ◽  
Nina J Mars ◽  
Sanni Söderlund ◽  
Christian Benner ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Cumulative Exposure ◽  
Risk Scores ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

AbstractBackgroundHyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). Monogenic familial hypercholesterolemia associates with higher increase in CAD risk than expected from a single LDL-C measurement, likely due to lifelong cumulative exposure to high LDL-C. It remains unclear to what extent a high polygenic load of LDL-C or TG-increasing variants associates with increased CAD risk.Methods and ResultsWe derived polygenic risk scores (PRS) with ∼6M variants for LDL-C and TG with weights from a UK biobank-based genome-wide association study with ∼500K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the FINRISK cohort, and to CAD risk in 135 300 individuals (13 695 CAD cases) from the FinnGen project.In FINRISK, LDL-C ranged from 2.83 (95% CI 2.79-2.89) to 3.80 (3.72-3.88) and TG from 0.99 (0.95-1.01) to 1.52 (1.48-1.58) mmol/l between the lowest and highest 5% of the respective PRS distributions. The corresponding CAD prevalences ranged from 8.2% to 12.7% for the LDL-C PRS and from 8.2% to 12.1% for the TG PRS in FinnGen. Furthermore, CAD risk was 1.36-fold higher (OR, 95% CI 1.24-1.49) for the LDL-C PRS and 1.31-fold higher (1.20-1.44) for the TG PRS for those with the PRS >95th percentile vs those without. These estimates were only slightly attenuated when adjusting for a CAD PRS (OR 1.26 [95% CI 1.15-1.39] for LDL-C and 1.21 [1.10-1.32] for TG PRS).ConclusionsThe CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and mostly independent of a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing more direct guidance for clinical translation.

scholarly journals Unique and Varied Contributions of Traditional CVD Risk Factors: A Systematic Literature Review of CAD Risk Factors in China

2013 ◽  
Vol 7 ◽  
pp. CMC.S10225 ◽  
Author(s):  
Joanne Foody ◽  
Yong Huo ◽  
Linong Ji ◽  
Dong Zhao ◽  
Dylan Boyd ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Real World ◽  
Odds Ratio ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

This study is the first systematic review of risk factors for stroke in China and supports the importance of current public health initiatives to manage the risk factors appropriately to reduce risk of stroke in high risk patients. Additionally, this study has been co-authored by prominent Chinese and US physicians and researchers with expertise in cardiovascular disease, neurologic disorders, epidemiology, and real world data. While there have been several systematic reviews of real world associations of risk factors for coronary artery disease, none focus specifically on the population of China, where there is growing evidence that such risk factors are poorly treated or uncontrolled, especially in rural areas. Background To better understand the impact of traditional cardiovascular risk factors on risk of coronary artery disease (CAD) in China, a systematic review of all Chinese observational studies published in either English or Chinese in MEDLINE and EMBASE over the last 5 years was performed and the association between any of 5 traditional risk factors (ie, hypertension, diabetes, elevated lipid levels, obesity, and smoking) and the risk of CAD was studied. Methods and Results The study found a consistent relationship between lipid levels and CAD. Higher low-density lipoprotein cholesterol values were associated with greater risk of CAD, with an odds ratio as high as 3.31. Other factors found to be significant contributors to the risk of CAD included hypertension (crude odds ratio range of 1.40-5.11), diabetes (1.50-5.97), and smoking (1.37-5.19). An association between obesity and CAD in China was observed, but the evidence supporting this was considered weak due to the paucity of studies found as part of this review. Conclusions This review provides a systematic summary of CAD risk factors in China and demonstrates the important differences that exist in CAD risk factors between countries and regions. Approaches to reduce CAD globally must take into account the unique risk factors that drive CAD in each country and region as is demonstrated by these findings.

scholarly journals Validation of genome-wide polygenic risk scores for coronary artery disease in French Canadians

2019 ◽  
Author(s):  
Florian Wünnemann ◽  
Ken Sin Lo ◽  
Alexandra Langford-Avelar ◽  
David Busseuil ◽  
Marie-Pierre Dubé ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Scores ◽  
French Canadian ◽  
French Canadians ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

AbstractCoronary artery disease (CAD) represents one of the leading causes of morbidity and mortality worldwide. Given the healthcare risks and societal impacts associated with CAD, their clinical management would benefit from improved prevention and prediction tools. Polygenic risk scores (PRS) based on an individual’s genome sequence are emerging as potentially powerful biomarkers to predict the risk to develop CAD. Two recently derived genome-wide PRS have shown high specificity and sensitivity to identify CAD cases in European-ancestry participants from the UK Biobank. However, validation of the PRS predictive power and transferability in other populations is now required to support their clinical utility. We calculated both PRS (GPSCAD and metaGRSCAD) in French-Canadian individuals from three cohorts totaling 3639 prevalent CAD cases and 7382 controls, and tested their power to predict prevalent, incident and recurrent CAD. We also estimated the impact of the founder French-Canadian familial hypercholesterolemia deletion (LDLR delta > 15kb deletion) on CAD risk in one of these cohorts and used this estimate to calibrate the impact of the PRS. Our results confirm the ability of both PRS to predict prevalent CAD comparable to the original reports (area under the curve (AUC) = 0.72-0.84). Furthermore, the PRS identified about 6-7% of individuals at CAD risk similar to carriers of the LDLR delta > 15kb mutation, consistent with previous estimates. However, the PRS did not perform as well in predicting incident (AUC= 0.56 - 0.60) or recurrent (AUC= 0.56 - 0.60) CAD. This result suggests that additional work is warranted to better understand how ascertainment biases and study design impact PRS for CAD. Collectively, our results confirm that novel, genome-wide PRS are able to predict CAD in French-Canadians; with further improvements, this is likely to pave the way towards more targeted strategies to predict and prevent CAD-related adverse events.

An Overview of Genetic Factors Influencing Plasma Lipid Levels and Coronary Artery Disease Risk

1999 ◽  
Vol 123 (12) ◽  
pp. 1219-1222 ◽  
Author(s):  
I. Cetin Ozturk ◽  
Anthony A. Killeen
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Disease Risk ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Major Effect ◽  
Genetic Component ◽  
Cholesterol Acyl Transferase ◽  
Artery Disease ◽  
Cad Risk

Abstract Background.—Coronary artery disease (CAD) is a major cause of morbidity and mortality in most Western countries and its origin involves a significant genetic component. Methods.—Genetic and epidemiologic studies have been performed to identify factors that influence the CAD risk in the population. Results.—The primary loci that have been demonstrated to be associated with increased CAD risk owing to genetic mutations include the low-density lipoprotein receptor, apolipoprotein B-100, and lipoprotein(a). Additional implicated loci include lipoprotein lipase, apolipoprotein CII, cholesteryl ester transfer protein, apolipoprotein AI, and lecithin–cholesterol acyl transferase. Conclusions.—Numerous mutations in known genes exert a major effect on CAD risk in some patients. However, in most patients with CAD, the genetic component is believed to be attributable to the aggregate effect of loci that, individually, exert only a minor influence on lipoprotein levels.

scholarly journals Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association

Circulation ◽  
2021 ◽  
Author(s):  
Tiffany M. Powell-Wiley ◽  
Paul Poirier ◽  
Lora E. Burke ◽  
Jean-Pierre Després ◽  
Penny Gordon-Larsen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Weight Loss ◽  
Coronary Artery ◽  
Disease Risk ◽  
Artery Disease ◽  
The Impact

The global obesity epidemic is well established, with increases in obesity prevalence for most countries since the 1980s. Obesity contributes directly to incident cardiovascular risk factors, including dyslipidemia, type 2 diabetes, hypertension, and sleep disorders. Obesity also leads to the development of cardiovascular disease and cardiovascular disease mortality independently of other cardiovascular risk factors. More recent data highlight abdominal obesity, as determined by waist circumference, as a cardiovascular disease risk marker that is independent of body mass index. There have also been significant advances in imaging modalities for characterizing body composition, including visceral adiposity. Studies that quantify fat depots, including ectopic fat, support excess visceral adiposity as an independent indicator of poor cardiovascular outcomes. Lifestyle modification and subsequent weight loss improve both metabolic syndrome and associated systemic inflammation and endothelial dysfunction. However, clinical trials of medical weight loss have not demonstrated a reduction in coronary artery disease rates. In contrast, prospective studies comparing patients undergoing bariatric surgery with nonsurgical patients with obesity have shown reduced coronary artery disease risk with surgery. In this statement, we summarize the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation. In particular, we examine the influence of obesity on noninvasive and invasive diagnostic procedures for coronary artery disease. Moreover, we review the impact of obesity on cardiac function and outcomes related to heart failure with reduced and preserved ejection fraction. Finally, we describe the effects of lifestyle and surgical weight loss interventions on outcomes related to coronary artery disease, heart failure, and atrial fibrillation.

scholarly journals The Synergistic Effect of Plasminogen Activator Inhibitor-1 (PAI-1) Polymorphisms and Metabolic Syndrome on Coronary Artery Disease in the Korean Population

2020 ◽  
Vol 10 (4) ◽  
pp. 257
Author(s):  
Han Sung Park ◽  
Jung-Hoon Sung ◽  
Chang Soo Ryu ◽  
Jeong Yong Lee ◽  
Eun Ju Ko ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Coronary Artery ◽  
Synergistic Effect ◽  
Odds Ratio ◽  
Metabolic Syndrome Component ◽  
The Metabolic Syndrome ◽  
Artery Disease ◽  
Cad Risk ◽  
Pai 1

The most common type of cardiovascular disease is coronary artery disease (CAD), in which a plaque builds up inside the coronary arteries that can lead to a complete blockage of blood flow to the heart, resulting in a heart attack. The CAD may be affected by various factors including age, gender, and lipoprotein disposition as well as genetic factors and metabolic syndrome. In this study, we investigated whether three PAI-1 polymorphisms (−844 G > A, −675 4G > 5G, and +43 G > A) and CAD-related clinical parameters are associated with CAD susceptibility. Genotyping of 463 CAD patients and 401 controls was performed using polymerase chain reaction restriction fragment length polymorphism analysis. We report that the 4G5G genotype (crude odds ratio(COR), 1.392; 95% confidence interval (CI), 1.036–1.871; p = 0.028) and dominant model (4G4G vs. 4G5G + 5G5G; COR, 1.401; 95% CI, 1.060–1.850; p = 0.018; adjust odds ratio, 1.371; 95% CI, 1.027–1.831; p = 0.032) of PAI-1 −675 polymorphisms were associated with increased CAD risk. Haplotype and genotype combinations of PAI-1 −675 and +43 polymorphisms show an increased risk of CAD according to alterations of the −675 polymorphism allele or genotype. Moreover, the PAI-1 -675 polymorphisms show a synergistic effect with the metabolic syndrome component of CAD risk. This study suggests that polymorphisms in the PAI-1 genes along with the metabolic syndrome component of CAD can be useful biomarkers for CAD diagnosis and treatment.

scholarly journals Polygenic Scores to Assess Atherosclerotic Cardiovascular Disease Risk

2020 ◽  
Vol 126 (9) ◽  
pp. 1159-1177 ◽  
Author(s):  
Krishna G. Aragam ◽  
Pradeep Natarajan
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Clinical Utility ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Risk Scores ◽  
Atherosclerotic Cardiovascular Disease ◽  
Artery Disease ◽  
Atherosclerotic Cardiovascular Disease Risk

An individual’s susceptibility to atherosclerotic cardiovascular disease is influenced by numerous clinical and lifestyle factors, motivating the multifaceted approaches currently endorsed for primary and secondary cardiovascular disease prevention. With growing knowledge of the genetic basis of atherosclerotic cardiovascular disease—in particular, coronary artery disease—and its contribution to disease pathogenesis, there is increased interest in understanding the potential clinical utility of a genetic predictor that might further refine the assessment and management of atherosclerotic cardiovascular disease risk. Rapid scientific and technological advances have enabled widespread genotyping efforts and dynamic research in the field of coronary artery disease genetic risk prediction. In this review, we describe how genomic analyses of coronary artery disease have been leveraged to create polygenic risk scores. We then discuss evaluations of the clinical utility of these scores, pertinent mechanistic insights gleaned, and practical considerations relevant to the implementation of polygenic risk scores in the health care setting.

scholarly journals Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Majid Nikpay ◽  
Ruth McPherson
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Protein Level ◽  
Human Leukocyte ◽  
Trait Loci ◽  
Artery Disease ◽  
Associated Risk Factors ◽  
The Impact ◽  
Cad Risk

AbstractHere we seek to identify molecular biomarkers that mediate the effect of risk factors on coronary artery disease (CAD). We perform a SNP-based multiomics data analysis to find biomarkers (probes) causally associated with the risk of CAD within known genomic loci for its risk factors. We identify 78 biomarkers, the majority (64%) of which are methylation probes. We detect the convergence of several CNS and lifestyle trait loci and their biomarkers at the 3p21.31 and human leukocyte antigen (HLA) regions. The 3p21.31 locus was the most populated region in the convergence of biomarkers and risk factors. In this region, we noted as the BSN gene becomes methylated the level of stomatin (STOM) in blood increases and this contributes to higher risk of CAD. In the HLA locus, we identify several methylation biomarkers associated with various CAD risk factors. SNPs in the CFB gene display a trans-regulatory impact on the GRIA4 protein level. A methylation site upstream of the APOE gene is associated with a higher protein level of S100A13 which in turn leads to higher LDL-C and greater CAD risk. We find UHRF1BP1 and ILRUN mediate the effect of obesity on CAD whereas methylation sites within NOS3 and CKM mediate the effect of their associated-risk factors on CAD. This study provides further insight into the biology of CAD and identifies a list of biomarkers that mediate the impact of risk factors on CAD. A SNP-based initiative can unite data from various fields of omics into a single network of knowledge.

Abstract 534: A Common Null Allele of LPA is Associated With Lp(a) Levels and Coronary Artery Disease Risk

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Theodosios Kyriakou ◽  
Udo Seedorf ◽  
Anuj Goel ◽  
Jemma C Hopewell ◽  
Robert Clarke ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Null Allele ◽  
Disease Risk ◽  
Case Control ◽  
Control Cohort ◽  
Apolipoprotein A ◽  
Artery Disease ◽  
The Relationship ◽  
Cad Risk

Objective: Increased levels of Lp(a) lipoprotein are a highly heritable risk factor for coronary artery disease (CAD). The genetic determinants of Lp(a) levels are mainly due to genetic variation in the apolipoprotein(a) gene (LPA). We have tested the association of a null allele of LPA with Lp(a) levels and CAD risk in a large case-control cohort. We have also examined how null allele genotyping complements apolipoprotein(a) isoform typing to refine the relationship between LPA isoform size and circulating Lp(a) levels. Approach and Results: The LPA null allele (rs41272114) was genotyped in the PROCARDIS case-control cohort (4,073 CAD cases, 4,225 controls). Lp(a) lipoprotein levels were measured in 909 CAD cases and 922 controls; apolipoprotein(a) isoform size was estimated using SDS-agarose gel electrophoresis and a high-throughput qPCR based method. Null carriers are common (null allele frequency 3%) and have significantly lower circulating Lp(a) levels (p=2.1x10-10) and reduced CAD risk (p=0.023) compared to non-carriers. An additive allelic model of apolipoprotein(a) isoform size, refined by null allele genotype and qPCR values, showed a sigmoid relationship with Lp(a) levels with baseline levels for longer isoform alleles and progressively higher levels of Lp(a) for shorter isoform alleles. Conclusions: The LPA null allele (rs41272444) is associated with decreased circulating Lp(a) levels and decreased CAD risk. A joint genomic and isoform analysis revealed details of the relationship between apolipoprotein(a) isoform size and circulating Lp(a) level consistent with a threshold effect on lipoprotein secretion.

scholarly journals Metabolic Syndrome and Coronary Artery Disease Risk: A Meta-Analysis of Observational Studies

2021 ◽  
Vol 18 (4) ◽  
pp. 1773
Author(s):  
Amal F. Alshammary ◽  
Khalid Khalaf Alharbi ◽  
Naif Jameel Alshehri ◽  
Vishal Vennu ◽  
Imran Ali Khan
Keyword(s):  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Coronary Artery ◽  
Observational Studies ◽  
Web Of Science ◽  
Disease Risk ◽  
Meta Analysis ◽  
Coronary Artery Disease Risk ◽  
Artery Disease ◽  
Cad Risk

Although numerous studies have described the link between metabolic syndrome (MetS) and Coronary Artery Disease (CAD), no meta-analysis has been carried out on this relationship. Thus, the present study intended to address this limitation. A systematic search was carried out using electronic databases, such as PubMed, CINAHL Plus, Medline, and Web of Science. A sum of 10 studies (n = 9327) was incorporated in the meta-analysis. Compared with non-MetS, MetS was significantly associated with high CAD risk (OR = 4.03, 95% CI = 3.56–4.56). The MetS components were also significantly correlated with high CAD risk (OR = 3.72, 95% CI = 3.22–4.40). The presence of two (OR = 3.93, 95% CI = 2.81–5.49), three (OR = 4.09, 95% CI = 2.85–5.86), four (OR = 4.04, 95% CI = 2.83–5.78), or all five MetS components (OR = 3.92, 95% CI = 3.11–4.93), were significantly associated with a high risk of CAD. MetS and its individual or combined elements were linked with high CAD risk based on contemporary evidence. Thus, the assessment of MetS and its components might help identify people at a higher risk of advancing CAD in the future.

Sign in / Sign up

Export Citation Format

Share Document