Fixed Traits, Changeable Paths: What We Inherit, What We Influence, and the Future of Coronary Health

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide [1]. Coronary computed tomography angiography (CCTA) is a powerful tool for ruling out CAD in patients with stable chest pain or symptoms that can mimic myocardial ischemia [2]. In asymptomatic patients, CAD presence can be estimated regardless of stenosis degree by evaluating coronary artery calcium score (CACS) on non-contrast ECG-gated CT [3]. CACS is an important prognostic marker; patients with high calcium scores have worse outcomes [4]. Several articles have demonstrated the prognostic impact of CACS in patients with suspected CAD. However, CACS values vary significantly by age and sex [5] and may indicate plaque burden or the presence of stable coronary calcified plaques [6], which are less likely to cause acute myocardial ischemic events. Kerut et al. [7] developed predictive models using cardiovascular risk factors and clinical data to calculate the probability of having specific CACS values approximately one decade into the future. Their cohort included 656 Black participants from the GENOA study. They created three models to predict CACS of zero, greater than 10, and greater than 100, achieving ROC values of 0.78, 0.77, and 0.76 respectively. Age, height, smoking duration, sex, and hypertension were common predictive factors across all models. Interestingly, patients receiving antihypertensive therapy had a lower probability of CACS zero and higher probability of CACS ≥ 10 and CACS ≥ 100. One unexpected finding was that height showed an inverse correlation with future CACS: greater height was associated with a higher probability of CACS zero and lower probability of elevated CACS. The study did not demonstrate any significant relationship between weight or BMI and future CAC burden. As expected, women had lower probabilities of elevated CACS compared to men. Smoking emerged as the strongest modifiable risk factor. The study also confirmed the so-called “CACS paradox”: lipid-lowering medications were associated with increased CACS, likely reflecting plaque stabilization and conversion from noncalcified to calcified plaque rather than disease progression. The ability to predict the general range of coronary calcium scores and plaque burden a decade in advance using traditional cardiovascular risk factors could potentially motivate earlier preventive lifestyle modifications. These CT findings support the concept that lifestyle modification can influence CACS values, reflecting plaque burden and potentially reducing the probability of acute ischemic myocardial events. Smoking was consistently one of the most influential factors associated with high CACS values in all models analyzed. This finding reinforces the importance of evaluating CACS during lung cancer screening programs, given the established relationship between CAD development and lung cancer [8]. The “CACS paradox” found in the study of Kerut et al. [7] is another important finding: high CACS values after statin therapy could indicate a change in coronary plaque phenotype to a more calcified and stable form, reflecting stabilization of CAD progression. CACS should be contextualized based on the patient's clinical history and could show both plaque burden and CAD stabilization. This article raises important questions about primary prevention and CAD. Our lifestyle choices today essentially determine our cardiovascular health decades from now, influenced by our clinical predisposition. Even when high CACS values reflect stable coronary plaque compositions, this can lead to chronic stable ischemia with reduced quality of life. The study's main limitation is the lack of ethnic diversity in the cohort. Nevertheless, an important clinical message emerges: there is a window in every patient's clinical history where CAD progression can still be slowed or halted while the disease remains subclinical. We should not miss this opportunity to intervene before our patients pay the price with their health.