Association Between Family History, a Genetic Risk Score, and Severity of Coronary Artery Disease in Patients With Premature Acute Coronary Syndromes

Hindieh, Waseem; Pilote, Louise; Cheema, Asim N.; Al-Lawati, Hatim; Labos, Christopher; Dufresne, Line; Engert, James C.; Thanassoulis, George

doi:10.1161/atvbaha.115.306944

Cited by 48 publications

(28 citation statements)

References 46 publications

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“…(43) Due to lack of data, we could not confirm whether the effect of genetic profiling on fracture risk is dependent on parental history variable. However, studies in the field of cardiovascular disease have suggested that the effect of genetic profiling on coronary heart disease (44,45) is independent of family history.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling

Ho-Le

Center

Eisman

et al. 2016

Journal of Bone and Mineral Research

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Although the susceptibility to fracture is partly determined by genetic factors, the contribution of newly discovered genetic variants to fracture prediction is still unclear. This study sought to define the predictive value of a genetic profiling for fracture prediction. Sixty-two bone mineral density (BMD)-associated single-nucleotide polymorphisms (SNPs) were genotyped in 557 men and 902 women who had participated in the Dubbo Osteoporosis Epidemiology Study. The incidence of fragility fracture was ascertained from X-ray reports between 1990 and 2015. Femoral neck BMD was measured by dual-energy X-ray absorptiometry. A weighted polygenic risk score (genetic risk score [GRS]) was created as a function of the number of risk alleles and their BMD-associated regression coefficients for each SNP. The association between GRS and fracture risk was assessed by the Cox proportional hazards model. Individuals with greater GRS had lower femoral neck BMD (p < 0.01), but the variation in GRS accounted for less than 2% of total variance in BMD. Each unit increase in GRS was associated with a hazard ratio of 1.20 (95% CI, 1.04 to 1.38) for fracture, and this association was independent of age, prior fracture, fall, and in a subset of 33 SNPs, independent of femoral neck BMD. The significant association between GRS and fracture was observed for the vertebral and wrist fractures, but not for hip fracture. The area under the receiver-operating characteristic (ROC) curve (AUC) for the model with GRS and clinical risk factors was 0.71 (95% CI, 0.68 to 0.74). With GRS, the correct reclassification of fracture versus nonfracture ranged from 12% for hip fracture to 23% for wrist fracture. A genetic profiling of BMD- associated genetic variants could improve the accuracy of fracture prediction over and above that of clinical risk factors alone, and help stratify individuals by fracture status. © 2016 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling

Ho-Le

Center

Eisman

et al. 2016

Journal of Bone and Mineral Research

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“…As performed previously [15], we defined multivessel stenosis as having at least two lesions, each with ≥ 50% stenosis, influencing at least two of the four major coronary arteries (left main coronary artery, right coronary artery, left circumflex artery and left anterior descending artery). Each stenotic lesion was graded by a board-certified cardiologist who had additional training in angiography.…”

Section: Definition Of Atherosclerotic Burden In the Mccd Cohortmentioning

confidence: 99%

Polygenic risk for coronary heart disease acts through atherosclerosis in type 2 diabetes

Forgetta

et al. 2020

Cardiovasc Diabetol

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Background: Type 2 diabetes increases the risk of coronary heart disease (CHD), yet the mechanisms involved remain poorly described. Polygenic risk scores (PRS) provide an opportunity to understand risk factors since they reflect etiologic pathways from the entire genome. We therefore tested whether a PRS for CHD influenced risk of CHD in individuals with type 2 diabetes and which risk factors were associated with this PRS. Methods:We tested the association of a CHD PRS with CHD and its traditional clinical risk factors amongst individuals with type 2 diabetes in UK Biobank (N = 21,102). We next tested the association of the CHD PRS with atherosclerotic burden in a cohort of 352 genome-wide genotyped participants with type 2 diabetes who had undergone coronary angiograms. Results:In the UK Biobank we found that the CHD PRS was strongly associated with CHD amongst individuals with type 2 diabetes (OR per standard deviation increase = 1.50; p = 1.5 × 10 − 59 ). But this CHD PRS was, at best, only weakly associated with traditional clinical risk factors, such as hypertension, hyperlipidemia, glycemic control, obesity and smoking. Conversely, in the angiographic cohort, the CHD PRS was strongly associated with multivessel stenosis (OR = 1.65; p = 4.9 × 10 − 4 ) and increased number of major stenotic lesions (OR = 1.35; p = 9.4 × 10 − 3 ). Conclusions:Polygenic predisposition to CHD is strongly associated with atherosclerotic burden in individuals with type 2 diabetes and this effect is largely independent of traditional clinical risk factors. This suggests that genetic risk for CHD acts through atherosclerosis with little effect on most traditional risk factors, providing the opportunity to explore new biological pathways.

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“…In this study, it was also shown that the CAD is more severe among patients with a positive family history of heart disease than among patients without a positive family history. [31] Other studies on 349 individuals who had referred for angiography were researched by Sunman et al . Patients with a positive family history of heart disease suffered from a higher severity of CAD.…”

Section: Discussionmentioning

confidence: 99%

Assessment of risk factors for coronary artery disease in military personnel: A study from Iran

Mirzaeipour

Seyedmazhari

Pishgooie

et al. 2019

J Family Med Prim Care

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Introduction: Cardiovascular diseases are the most significant cause of mortality. Although the risk factors of this disease are well known, the strength of these factors varies in different populations and needs to be investigated. Aim: The aim of this study is to estimate the amount of the effect of each classic risk factor on CAD (coronary artery disease) among Aja personnel. Materials and Methods: This matched case-control study was conducted on 1000 male Aja personnel admitted selecting Aja hospitals in Tehran in 2017. The samples were selected using purposive-graded sampling method. The 250 military patients hospitalized for CAD were considered as a case group. Each case was individually matched for age and service force with tree military patients without CAD. Data were gathered using standard demographic information and history of risk factors questionnaire and analyzed using SPSS 23 and statistical tests. Odds ratio measured trough Cochran–Mantel–Haenszel test and used to estimate the amount of the effect of each classic risk factors on CAD. Results: Data analysis indicated that the risk factors including diabetes, hyperlipidemia, smoking, hypertension, and positive family history of CAD enhance the probability of CAD as much as 79.2%, 77.3%, 67.7%, 64.1%, and 56.6%, respectively. Conclusion: Diabetes and other modifiable risk factors have the greatest impact on CAD among the concerned Aja personnel. Hence, the authorities can consider the independent amount of the effect of each risk factor and modify them in order to prevent the disease more effectively and purposefully among the personnel.

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Association Between Family History, a Genetic Risk Score, and Severity of Coronary Artery Disease in Patients With Premature Acute Coronary Syndromes

Cited by 48 publications

References 46 publications

Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling

Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling

Polygenic risk for coronary heart disease acts through atherosclerosis in type 2 diabetes

Assessment of risk factors for coronary artery disease in military personnel: A study from Iran

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