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Coronary Plaque, LDL-C Levels, and Rates of CVD Events
Quick Takes
- Atherosclerotic burden is heterogeneous across the spectrum of LDL-C levels, and risk is consistently associated with plaque burden.
- Measurement of atherosclerosis burden, including assessment of CAC, may be used to individualize treatment intensity by identifying patients who are at low risk despite having severely elevated LDL-C levels.
- Longer follow-up of people with severe hypercholesterolemia and absence of CAC or plaques are indicated to confirm these study findings to help improve stratification and to guide intensity of LDL-C level–lowering therapies, even in this high-risk group.
Study Questions:
What is the prevalence of noncalcified and calcified plaque in symptomatic adults and its association with cardiovascular disease (CVD) events across the low-density lipoprotein cholesterol (LDL-C) spectrum?
Methods:
The investigators conducted a cohort study of symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Prevalence of calcified and noncalcified plaque according to LDL-C strata of <77, 77-112, 113-154, 155-189, and ≥190 mg/dL was ascertained. Severity of coronary artery disease was categorized using coronary artery calcium (CAC) scores of 0, 1-99, and ≥100, where higher numbers indicate greater CAC burden. The main outcomes and measures were atherosclerotic CVD (ASCVD) events (myocardial infarction and stroke) and death.
Results:
A total of 23,143 patients with a median age of 58 (interquartile range [IQR], 50-65) years (12,857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1,029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of ≥190 mg/dL to 4,370 of 7,964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of ≥190 mg/dL to 1,067 of 1,204 (88.6%) in those with LDL-C levels of <77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1,000 person-years), with increasing rates in patients with CAC scores of 1-99 (11.1 [95% CI, 10.0-12.5] per 1,000 person-years) and CAC scores of ≥100 (21.9 [95% CI, 19.9-24.4] per 1,000 person-years). Among those with CAC scores of 0, the event rate per 1,000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of ≥190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque.
Conclusions:
The authors concluded that in symptomatic patients with severely elevated LDL-C levels of ≥190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events.
Perspective:
This study reports that atherosclerotic burden is heterogeneous across the spectrum of LDL-C levels, and risk is consistently associated with plaque burden. Of note, absence of plaque was noted in 46.2% of patients with LDL-C levels of ≥190 mg/dL. Furthermore, absence of plaque and CAC was associated with low event rates across the LDL-C spectrum. Overall, these data suggest that measurement of atherosclerosis burden, including assessment of CAC, may be used to individualize treatment intensity by identifying patients who are at low risk despite having severely elevated LDL-C levels. Longer follow-up of people with severe hypercholesterolemia and absence of CAC or plaques are indicated to confirm these study findings and help improve stratification and guide intensity of LDL-C level–lowering therapies, even in this so-called high-risk group.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging
Keywords: Atherosclerosis, Cardiometabolic Risk Factors, Cholesterol, LDL, Coronary Angiography, Coronary Artery Disease, Diagnostic Imaging, Dyslipidemias, Hypercholesterolemia, Myocardial Infarction, Myocardial Ischemia, Plaque, Atherosclerotic, Primary Prevention, Stroke, Vascular Diseases
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