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Determinants of ASCVD Events in Those With Absent CAC
Quick Takes
- Among individuals without coronary artery calcium (CAC = 0), cigarette smoking (CHD), diabetes mellitus, and hypertension (stroke) are independently associated with incident ASCVD events over long-term follow-up.
- The findings refute the warranty of a CAC = 0 against ASCVD events for major risk factors with the exception of delaying statins for high LDL-C.
- Among persons with CAC = 0 who are current smokers, have diabetes or hypertension, and women with family history of premature ASCVD, initiation of long-term statin therapy, a healthy lifestyle, and risk factor modification may be warranted as part of the clinician patient risk discussion.
Study Questions:
Are traditional cardiovascular risk factors associated with incident atherosclerotic cardiovascular disease (ASCVD) in persons with a coronary artery calcium score (CAC) = 0 when followed long-term?
Methods:
The authors used participants in the MESA (Multi-Ethnic Study of Atherosclerosis) prospective cohort study free of clinical ASCVD and with a baseline CAC = 0. Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors (cigarette smoking, diabetes mellitus, hypertension, systolic blood pressure ≥130 mm Hg and diastolic blood pressure ≥80 mm Hg), preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes.
Results:
There were 3,416 individuals (mean [standard deviation] age, 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese-American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease [CHD] and stroke), of which 91 were CHD, 88 were stroke, and 10 were both CHD and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1,000 person-years among individuals with CAC = 0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes mellitus (8.9), hypertension (5.4), and chronic kidney disease (6.8) (each per 1,000 person-years). After multivariable adjustment, risk factors that were significantly associated with ASCVD (hazard ratio and 95% confidence interval) included current cigarette smoking: 2.12 (1.32, 3.42), diabetes mellitus: 1.68 (1.01, 2.80), and hypertension: 1.57 (1.06, 2.33).
Conclusions:
Current cigarette smoking, diabetes mellitus, and hypertension are independently associated with incident ASCVD over 16-year follow-up among those with CAC = 0. Family history of premature ASCVD may be associated with ASCVD risk among women only.
Perspective:
CAC score has a Class IIa recommendation to guide statin treatment in persons who are borderline or intermediate 10-year risk of ASCVD. CAC = 0 is associated with low risk of ASCVD and may be used to justify withholding or postponing statin therapy if there is clinical uncertainty. The 2018 American Heart Association/American College of Cardiology cholesterol guideline endorses statin therapy despite CAC = 0 in diabetics, current smokers, or those with a strong family history of premature ASCVD because of the higher risk of ASCVD events over 10 years. This study extended the analysis by adding advanced lipid and inflammatory markers to the conventional cardiovascular risk factors to assess whether they are independently associated with incident ASCVD in those with baseline CAC = 0 over a long-term follow-up. None of the ‘risk enhancers’ predicted ASCVD in those with CAC = 0, nor significant association of incident cardiovascular risk factors and incident ASCVD.
Clinical Topics: Cardiovascular Care Team, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Hypertension, Smoking
Keywords: Aspirin, Atherosclerosis, Blood Pressure, Coronary Disease, Cigarette Smoking, Diabetes Mellitus, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Inflammation, Lipids, Plaque, Atherosclerotic, Primary Prevention, Renal Insufficiency, Chronic, Risk Factors, Smoking, Stroke, Waist Circumference
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