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Published on: September 26, 2018
Importance of Clinical, Laboratory, and Genetic Risk Factors for Incident CAD
Romit Bhattacharya1,2, Christopher S Marnell3, So Mi Jemma Cho1,2,4
1Department of Medicine, Harvard Medical School (R.B., A.P., A.J., S.H., K.L., M.C.H., P.N.), Massachusetts General Hospital, Boston.
Insights
Novel cardiovascular risk factors, including polygenic risk scores, hsCRP, and Lp(a), are as important as traditional factors like hypertension for preventing myocardial infarction. These findings identify key residual risks for heart attack prevention.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Preventive Cardiology
Background:
- Modifiable cardiovascular risk factors (CRFs) are estimated to cause 80-90% of myocardial infarctions.
- Previous studies have not simultaneously evaluated genetic and novel CRFs alongside traditional ones.
Purpose of the Study:
- To assess the contributions of traditional, contemporary, and genetic CRFs to incident myocardial infarction.
- To identify key residual risk factors for coronary artery disease.
Main Methods:
- Utilized data from the UK Biobank, including 299,707 individuals.
- Constructed Cox proportional hazards models incorporating traditional CRFs (hypertension, diabetes, dyslipidemia, etc.) and novel/genetic CRFs (Lp(a), hsCRP, familial hypercholesterolemia variants, polygenic risk score).
- Calculated the percent contribution of each CRF by measuring the R-squared decrease upon its removal from the model.
Main Results:
- The contemporary/genetic model (R-squared 0.053) showed a higher predictive value than the clinical model (R-squared 0.045) and base model (R-squared 0.021).
- Hypertension (15.2% R-squared loss) and polygenic risk score for coronary artery disease (12.4% R-squared loss) were the most significant individual CRFs.
- Novel factors like hsCRP (1.8% R-squared loss) and Lp(a) (1.5% R-squared loss) demonstrated notable contributions.
Conclusions:
- Novel CRFs, including polygenic risk scores, hsCRP, and Lp(a), possess importance comparable to traditional CRFs for predicting myocardial infarction.
- These findings underscore the significance of these factors in identifying residual risk for coronary artery disease.
Background:
Prior work suggests modifiable cardiovascular risk factors (CRFs) account for 80% to 90% of the risk for incident myocardial infarction. The contributions of genetic and other novel CRFs have not been simultaneously assessed in contemporary data sets.
Methods:
In the United Kingdom Biobank, CRFs were identified and Cox proportional hazards models with traditional CRFs (hypertension, diabetes, dyslipidemia, waist-to-hip ratio, diet, exercise, alcohol, and socioeconomic deprivation) and contemporary/genetic CRFs (Lp(a) [lipoprotein(a)], hsCRP [high-sensitivity C-reactive protein], familial hypercholesterolemia variants, and polygenic risk score for coronary artery disease) were constructed for coronary artery disease. Coronary artery disease was defined as a first-time myocardial infarction diagnosis or coronary revascularization. R2 was calculated for each model, and the percent contribution of each individual CRF was calculated by the R2 percent decrease after its removal.
Results:
Among 299 707 individuals, the mean (SD) age was 56.2 (8.1) years, and 166 533 (55.6%) were women. Over a median (interquartile range) follow-up of 11.0 (9.6-12.5) years, 17 409 (5.8%) of participants developed myocardial infarction. R2 increased from the base model (R2, 0.021 [0.020-0.022]), to the clinical model (R2, 0.045 [0.043-0.046]), to the contemporary/genetic model (R2, 0.053 [0.052-0.055]). The most powerful individual CRFs were hypertension (R2 loss, 15.2% [14.5-17.1]) and polygenic risk score for coronary artery disease (R2 loss, 12.4% [10.8-13.3]), followed by dyslipidemia (R2 loss, 3.4% [2.6-3.5]), diabetes (R2 loss, 2.2% [1.5-2.0]), hsCRP (R2 loss, 1.8% [1.5-2.0]), and Lp(a) (R2 loss, 1.5% [1.2-1.8]).
Conclusions:
Novel CRFs like polygenic risk score for coronary artery disease, hsCRP, and Lp(a) have similar importance, comparable to traditional CRFs such as hypertension, dyslipidemia, and diabetes, for incident myocardial infarction, highlighting important identifiable residual risk factors.
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