Abstract
Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk. To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum. This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021. Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden. Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death. A total of 23 143 patients with a median age of 58 (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, 1029 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 at least 190 mg/dL to 4370 of 7964 [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 at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 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 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 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 at least 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. The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 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. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.
Highlights
US and European guidelines for the management of dyslipidemias in the prevention of atherosclerotic cardiovascular disease (ASCVD) provide strong recommendations for treating all patients with severe hypercholesterolemia with statins.[1,2] the 2019 dyslipidemia guidelines from the European Society of Cardiology universally classify patients with low-density lipoprotein cholesterol (LDL-C) levels of greater than 190 mg/dL as high-risk individuals, with an LDL-C treatment goal of less than 70 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 1000 person-years), with increasing rates in patients with CAC scores of 1 to (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least (21.9 [95% CI, 19.9-24.4] per 1000 person-years)
The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 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
Summary
US and European guidelines for the management of dyslipidemias in the prevention of atherosclerotic cardiovascular disease (ASCVD) provide strong recommendations (ie, class IA) for treating all patients with severe hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels Ն190 mg/dL) (to convert to mmol/L, multiply by 0.0259) with statins.[1,2] the 2019 dyslipidemia guidelines from the European Society of Cardiology universally classify patients with LDL-C levels of greater than 190 mg/dL as high-risk individuals, with an LDL-C treatment goal of less than 70 mg/dL. US and European guidelines for the management of dyslipidemias in the prevention of atherosclerotic cardiovascular disease (ASCVD) provide strong recommendations (ie, class IA) for treating all patients with severe hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels Ն190 mg/dL) (to convert to mmol/L, multiply by 0.0259) with statins.[1,2]. The 2019 dyslipidemia guidelines from the European Society of Cardiology universally classify patients with LDL-C levels of greater than 190 mg/dL as high-risk individuals, with an LDL-C treatment goal of less than 70 mg/dL. To achieve such a low LDL-C level in patients with severely elevated baseline levels, other therapies to lower lipid levels, such as ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, are needed despite use of maximally tolerated statin therapy.[1,2]. CAC burden has been shown to stratify risk among various other lipid disorders, allowing for the identification of individuals with lowest and highest event rates.[6]
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