Cardiovascular disease (CVD) remains a significant public health challenge, affecting individuals of all ages. In recent years, there has been a growing realization that risk assessment for CVD should extend beyond the traditional focus on older adults. Young adults, too, can be susceptible to CVD, and early identification of risk factors is crucial for preventive interventions. In a series of consecutive patients aged <50 years admitted for myocardial infarction, approximately 20% were aged < 40 years. They had similar risk profiles except for more substance abuse, smoking, and less hypertension. At-risk groups should be candidates for more intensive evaluation and management. Those with tobacco use, a family history of premature coronary heart disease, primary severe hypercholesterolemia, and diabetes mellitus would benefit from early intervention. So how do we improve risk stratification in young adults?
Pooled cohort equations are not designed for young adults under the age of 40 years of age. For young adults, 30-year or lifetime risk of a first ASCVD event should be used and can help with risk factor modification strategies. The 30-year risk model is based on the Framingham Heart Study and includes age, sex, systolic and diastolic blood pressure, total cholesterol, HDL and LDL cholesterol, history of diabetes, smoker, on HTN treatment, on statin treatment or on aspirin treatment. The presence of a family history of premature ASCVD in first-degree relatives <55 years in men and <65 years in women is a risk enhancer and prompts special assessment and treatment of risk factors such as hypertension, hypercholesterolemia, or diabetes. Ethnicity, particularly of South Asian ancestry, is associated with increased prevalence of insulin resistance diabetes.
Calcium score testing (CAC) using a CT scan allows the detection of atherosclerosis in relatively early stages. A non-contrast cardiac-gated CT of the heart is obtained with minimal radiation (<1 mSv) in 15 mins. There is an increasing interest in detecting low CAC burden in young adults at increased ASCVD risks. It is uncommon to find some coronary calcium before the age of 40, but men with risk factors of obesity, hypercholesterolemia, and hypertension constitute a higher risk group where a CAC >0 may confer prognostic relevance. Since the unit of measurement, the Agatston score is measured on an exponential scale, a 70-year-old man with a calcium score of 1,000 (defining the presence of coronary disease) would have had a CAC of 10 at the age of 40. The Walter Reed Cohort Study of over 13,000 young adults of 30-49 years, found that the presence and the severity of CAC >0 (0-100) were associated with an increased risk of ASCVD events over the follow-up period of 11 years.
POLYGENIC RISK SCORE
Heritability of coronary artery disease has been estimated to be around 40-60%. The genetic cause of coronary artery disease is composed of many genetic variants. Several genomic studies have identified the most common coronary disease-associated genetic variants. The combined effect size of each variant can explain heritability and the polygenic risk (PRS) that can be used to predict CAD. PRS is calculated using genome-wide association studies using germline DNA and can define the lifetime risk of developing CAD. Depending on the method used, there are multiple CAD-PRS. Risk prediction using PRS genetic susceptibility could develop into an innovative way to personalize primary prevention. The UK Biobank Cardiometabolic Consortium CHD Working group developed a CAD-PRS using 1.7 million genetic variants. PRS was tested and compared to traditional risk factors in over 22,000 patients with CAD and over 460,000 without CAD from the UK Biobank. Patients in the top 20% percentile had a 4 times higher risk of developing CAD compared to the group in the lowest percentile. In this study, the CAD-PRS did better for incident CAD than the 6 common risk factors: smoking, DM, HTN, Body mass index, self-reported high cholesterol, or family history. On the negative side, reproducibility, Eurocentric bias of population, and the potential for discrimination based on genetic risk. So, how the genetic risk is best related to the patients is an issue and necessitates a team approach integrating cardiology services and genetic counselors.