By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: Among those with a coronary calcium score of 0 after a median follow-up of 16 years, current cigarette smoking, diabetes, and hypertension were independently associated with the development of atherosclerotic cardiovascular disease.
SOURCE: Al Rifai M, Blaha MJ, Nambi V, et al. Determinants of incident atherosclerotic cardiovascular disease events among those with absent coronary artery calcium: Multi-Ethnic Study of Atherosclerosis. Circulation 2022;145:259-267.
Investigators from the Multi-Ethnic Study of Atherosclerosis (MESA) analyzed whether traditional atherosclerotic cardiovascular disease (ASCVD) risk factors and advanced lipid and inflammatory markers are independently associated with ASCVD events, even in those with a coronary calcium score (CAC) of 0 over a median follow-up of 16 years.
The MESA authors enrolled 6,814 U.S. subjects free of ASCVD age 45-84 years of white, Black, Hispanic, or Chinese race/ethnicity between 2000 and 2002 and conducted five follow-up visits up to 2018. The population for this analysis consisted of 3,416 subjects with a CAC score of 0 whose mean age was 58 years (63% women, 33% white, 31% Black, 24% Hispanic, and 12% Chinese). A pooled cohort equation measuring intermediate 10-year risk of ASCVD (7.5% to 19%) was present in 27%. During follow-up, 189 ASCVD events occurred, of which 91 were coronary, 88 were stroke, 10 were both, and 443 were all-cause deaths. After multivariate adjustment, risk factors associated with ASCVD events were current cigarette smoking (HR, 2.12; 95% CI, 1.32-3.42), diabetes (HR, 1.68; 95% CI, 1.01-2.80), and hypertension (HR, 1.57; 95% CI, 1.06-2.33). Smoking was associated mainly with coronary events and hypertension with stroke. The authors concluded that over a 16-year median follow-up, in those with a CAC score of 0, current cigarette smoking, diabetes, and hypertension were independently associated with incident ASCVD.
COMMENTARY
In patients with an intermediate risk of ASCVD, the 2018 guidelines provide a level IIa recommendation for CAC score determination and to withhold treatment with statins if such a score is 0. The caveat is those with diabetes, current cigarette smoking, or a strong family history of premature ASCVD should be treated, even if the CAC score is 0.1 However, a small proportion of patients with a CAC score of 0 will develop ASCVD, especially with long-term follow up. This study of the MESA database analyzed a longer follow-up than prior studies to determine the risk of ASCVD in CAC 0 patients. The authors showed ASCVD events were low, fewer than five per 1,000 patient-years in patients a median age of 58 years to 74 years.
However, current smoking, diabetes, and hypertension were associated with ASCVD events, and the event rates for smoking and diabetes almost achieved the 7.5% incidence threshold for statin therapy consideration according to the guidelines. Thus, the guideline caveat to treat smokers and diabetics with statins, even with a CAC score of 0, was supported by the results of this study. Also, these results suggest those with hypertension may be another caveat. A strong family history of premature ASCVD was not associated with ASCVD events in the MESA study of CAC 0 patients. However, when analyzed by sex, it was a significant risk factor in women.
With these caveats, this analysis supports the suggestion that it may be reasonable to not treat intermediate-risk patients with a CAC score of 0 with statins. Instead, clinicians may need to follow these patients closely for the development of other risk factors and perhaps repeat the CAC test after five years. The MESA analysis suggests a CAC score of 0 carries a 15-year warranty for most. However, a CT angiogram in patients with a CAC score of 0 might reveal soft plaques in some; withholding statins in CAC 0 patients is reasonable with the caveats mentioned.
There were limitations to the MESA study. The authors examined average event rates, which may not be evenly distributed (and could even increase with age), but this was not considered. Also, the study was underpowered to analyze the data by race/ethnicity. In addition, initiation of treatment for hypertension, hyperlipidemia, or smoking cessation after enrollment was not assessed adequately. Finally, the criteria for what constitutes high blood pressure have evolved over the course of the study. However, when the MESA authors used the various recommended definitions, the results were not significantly different. Nevertheless, MESA suggests that if borderline to intermediate risk for ASCVD patients balk at statin therapy, a CAC score determination is reasonable. If the score is 0, statins can be withheld as long as patients are not current smokers, diabetics, or hypertensive.
REFERENCE
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1082-e1143.
Among those with a coronary calcium score of 0 after a median follow-up of 16 years, current cigarette smoking, diabetes, and hypertension were independently associated with the development of atherosclerotic cardiovascular disease.
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