Coronary Heart Disease Genetic Risk Score Predicts Cardiovascular Disease Risk in Men, Not Women

Hajek, Catherine; Guo, Xiuqing; Yao, Jie; Hai, Yang; Johnson, W. Craig; Frazier‐Wood, Alexis C.; Post, Wendy S.; Psaty, Bruce M.; Taylor, Kent D.; Rotter, Jerome I.

doi:10.1161/circgen.118.002324

Cited by 25 publications

(25 citation statements)

References 3 publications

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“…Here we suggest, for the first time, the potential of circulating miRNAs to identify specific subgroups of patients. Similar to proposed genetic risk scores and risk assessment tools , circulating miRNAs lack biomarker value in the whole population, though such value may exist for selective subpopulations. For instance, according to our CHAID models, in the subgroup of male patients older than 64 years, miR‐143‐3p holds the potential to improve the diagnosis of those individuals with high coronary stenosis extension (SIS > 5) and severity (SSS > 5), and who are therefore at high risk for adverse events .…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs in suspected stable coronary artery disease: A coronary computed tomography angiography study

et al. 2019

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Objectives To explore the diagnostic performance of circulating microRNAs (miRNAs) as biomarkers in patients with suspected stable coronary artery disease (CAD). Methods Plasma samples were collected from 237 consecutive patients referred for coronary computed tomography angiography (CCTA). Presence, extension and severity of coronary stenosis were evaluated using the indexes: presence of diameter stenosis ≥ 50%, segment involvement score (SIS), segment stenosis score (SSS) and 3‐vessel plaque score. A panel of 10 miRNAs previously associated with CAD was analysed using RT‐qPCR. Multivariate analyses were used to analyse the associations between biomarkers and indexes. Discrimination was evaluated using the area under the ROC curve (AUC). Decision trees were generated using chi‐squared Automatic Interaction Detector (CHAID) prediction models. Results After comprehensive adjustment including cardiovascular risk factors, medication use, confounding factors and protein‐based biomarkers (hs‐TnT and hs‐CRP), several circulating miRNAs were inversely associated with coronary atherosclerosis extension (SIS and 3‐vessel plaque score) and severity (SSS). In the whole population, circulating miRNAs showed a poor discrimination value for all indexes (AUC = 0.539–0.644) and did not increase the discrimination capacity of a clinical model of coronary stenosis presence, extension and severity based on conventional cardiovascular risk factors. Conversely, the inclusion of circulating miRNAs in decision trees produces models that improve the classification of cases and controls in specific patient subgroups. Conclusions This study identifies a group of circulating miRNAs that failed to improve the discrimination capacity of cardiovascular risk factors but that has the potential to define specific subpopulations of patients with suspected stable CAD.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNAs in suspected stable coronary artery disease: A coronary computed tomography angiography study

et al. 2019

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“…The heritability of CHD has been estimated to be between 40 and 60% based on family, twin and genomewide association studies (GWAS) [8][9][10]. Genetic risk scores based on single nucleotide polymorphisms (SNPs) that are associated with coronary artery disease (CAD) have been shown to improve the risk prediction of CHD [11][12][13][14][15][16]. Most of these genetic studies used Framingham or established RFs to estimate the CHD risk.…”

Section: Introductionmentioning

confidence: 99%

“…Most of these genetic studies used Framingham or established RFs to estimate the CHD risk. A recent study from MESA could show an association between CAD genetic risk score and incident CHD only in men [11]. However, it has not been fully assessed i) whether the use of a CAD genetic risk score is superior to the measurement of CAC for CHD risk assessment and ii) whether the CHD risk assessment using a CAD genetic risk score differs between men and women.…”

Section: Introductionmentioning

confidence: 99%

Risk prediction for coronary heart disease by a genetic risk score - results from the Heinz Nixdorf Recall study

et al. 2020

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Background A Genetic risk score for coronary artery disease (CAD) improves the ability of predicting coronary heart disease (CHD). It is unclear whether i) the use of a CAD genetic risk score is superior to the measurement of coronary artery calcification (CAC) for CHD risk assessment and ii) the CHD risk assessment using a CAD genetic risk score differs between men and women. Methods We included 4041 participants (age-range: 45–76 years, 1919 men) of the Heinz Nixdorf Recall study without CHD or stroke at baseline. A standardized weighted CAD genetic risk score was constructed using 70 known genetic variants. The risk score was divided into quintiles (Q1-Q5). We specified low (Q1), intermediate (Q2-Q4) and high (Q5) genetic risk groups. Incident CHD was defined as fatal and non-fatal myocardial infarction, stroke and coronary death. The association between the genetic risk score and genetic risk groups with incident CHD was assessed using Cox models to estimate hazard ratios (HR) and 95%-confidence intervals (CI). The models were adjusted by age and sex (Model1), as well as by established CHD risk factors (RF) and CAC (Model2). The analyses were further stratified by sex and controlled for multiple testing. Results During a median follow-up time of 11.6 ± 3.7 years, 343 participants experienced CHD events (219 men). Per-standard deviation (SD) increase in the genetic risk score was associated with 18% increased risk for incident CHD (Model1: p = 0.002) which did not change after full adjustment (Model2: HR = 1.18 per-SD (p = 0.003)). In Model2 we observed a 60% increased CHD risk in the high (p = 0.009) compared to the low genetic risk group. Stratifying by sex, only men showed statistically significantly higher risk for CHD (Model2: HR = 1.23 per-SD (p = 0.004); intermediate: HR = 1.52 (p = 0.04) and high: HR = 1.88 (p = 0.008)) with no statistically significant risk observed in women. Conclusion Our results suggest that the CAD genetic risk score could be useful for CHD risk prediction, at least in men belonging to the higher genetic risk group, but it does not outbalance the value of CT-based quantification of CAC which works independently on both men and women and allows better risk stratification in both the genders.

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“…The TTE population was 53% male and had a mean age of 64 (standard deviation[s.d. ], 12) years (Supplementary Table 1). The most prevalent diagnoses were hypertension (81%), respiratory symptoms (75%), arrhythmias (68%) and lipid disorders (67%).…”

Section: Resultsmentioning

confidence: 99%

“…There were differences in the patterns of associations between men and women with respect to SBP and CAD. One explanation for the CAD difference is the fact that men at elevated CAD genetic risk are more likely to have CAD events, as compared to women with comparable genetic risk 12,13 . Thus, a CAD GRS is a poorer surrogate for CAD events among women, and this would lead to an attenuation of the association among women.…”

Section: Discussionmentioning

confidence: 99%

The polygenic architecture of left ventricular mass mirrors the clinical epidemiology

Mosley

Levinson

Farber‐Eger

et al. 2020

Sci Rep

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Left ventricular (LV) mass is a prognostic biomarker for incident heart disease and all-cause mortality. Large-scale genome-wide association studies have identified few SNPs associated with LV mass. We hypothesized that a polygenic discovery approach using LV mass measurements made in a clinical population would identify risk factors and diseases associated with adverse LV remodeling. We developed a polygenic single nucleotide polymorphism-based predictor of LV mass in 7,601 individuals with LV mass measurements made during routine clinical care. We tested for associations between this predictor and 894 clinical diagnoses measured in 58,838 unrelated genotyped individuals. There were 29 clinical phenotypes associated with the LV mass genetic predictor at FDR q < 0.05. Genetically predicted higher LV mass was associated with modifiable cardiac risk factors, diagnoses related to organ dysfunction and conditions associated with abnormal cardiac structure including heart failure and atrial fibrillation. Secondary analyses using polygenic predictors confirmed a significant association between higher LV mass and body mass index and, in men, associations with coronary atherosclerosis and systolic blood pressure. In summary, these analyses show that LV mass-associated genetic variability associates with diagnoses of cardiac diseases and with modifiable risk factors which contribute to these diseases. Left ventricular (LV) mass captures the cardiac response to the cumulative exposure of a diverse set of risk factors, and is strongly predictive of future cardiac events and all-cause mortality 1-3. Determining the genetic factors associated with LV mass could identify important predisposing mechanisms that contribute to heart disease. Three genome-wide association studies (GWAS) have only identified a single nucleotide polymorphism (SNP) associated with LV mass 4-6. Thus, the genetic architecture underlying LV mass remains uncharacterized.

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Coronary Heart Disease Genetic Risk Score Predicts Cardiovascular Disease Risk in Men, Not Women

Cited by 25 publications

References 3 publications

Circulating microRNAs in suspected stable coronary artery disease: A coronary computed tomography angiography study

Circulating microRNAs in suspected stable coronary artery disease: A coronary computed tomography angiography study

Risk prediction for coronary heart disease by a genetic risk score - results from the Heinz Nixdorf Recall study

The polygenic architecture of left ventricular mass mirrors the clinical epidemiology

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