Low ASCVD Risk in Patients With Elevated LDL-C Linked to Absence of Plaque

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Data show atherosclerotic burden was heterogeneous across LDL-C levels and risk is shown to be consistently associated with plaque burden.

New data suggest the absence of coronary artery calcium (CAC) and noncalcified plaque on coronary computed tomographic angiography (CCTA) was associated with low risk for atherosclerotic cardiovascular disease (ASCVD) events in symptomatic patients with severely elevated low-density lipoprotein cholesterol (LDL-C).

Investigators noted a number of additional factors beyond elevated LDL-C affected atherogenesis in the individual patient, despite it being the pathophysiologic causal agent in atherogenesis.

“Thus, the theoretical advantage of using information about coronary artery disease severity from CCTA in patients with high LDL-C levels is its ability to provide insight into the lifetime exposure to both known and unknown risk modifiers as well as the susceptibility for developing atherosclerosis in the individual patients,” said study author Martin Bødtker Mortensen, MD, PhD, Department of Cardiology, Aarhus University Hospital.

The study described the prevalence of calcified and noncalcified plaque in a large, phenotyped cohort of symptomatic patients undergoing CCTA assessment and additionally describe the association of the phenotypes with cardiovascular events across the following 5 LDL-C groups:

  • 77
  • 77 to 112
  • 113 to 154
  • 155 to 189
  • ≥190 mg/dL

Data was collected from the longitudinal health registry Western Denmark Heart Registry (WDHR). The study population consisted of all adult individuals (≥18 years old) from the WDHR undergoing CCTA from January 2008 - December 2017, due to symptoms suggesting coronary artery disease (CAD).

Severity of CAD was categorized according to the presence versus absence of obstructive disease based on the calcified atherosclerotic burden (CAC score: 0, 1- 99, and ≥100). Then, defined groups included no CAD (0% luminal stenosis and absence of any plaque), nonobstructive CAD (any plaque and <50% luminal stenosis), and obstructive CAD (>50% luminal stenosis).

A main composite endpoint was made up of myocardial infarction, ischemic stroke, and all-cause death occurring more than 90 days after a CCTA until first occurrence, or July 2018. Data were analyzed from April - December 2021.

The analysis included a total of 23,143 patients, at a median age of 58 years and made up of 55.6% women (n = 12,857). From a median of 4.2 years of follow-up, 1029 patients experienced a first event (myocardial infarction, n = 219; stroke, n = 299; death, n = 511).

Mortensen and colleagues stratified patients by presence of calcified plaque

  • CAC score, 0: 12,341 (55.3%)
  • CAC score, 1 to 99: 6282 (27.1%)
  • CAC score, ≥100: 4520 (19.5%)

Across LDL-C strata, the 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 4370 of 7964 (54.9%) in patients with LDL-C levels of 77 - 112 mg/dL.

It was associated with no detectable plaque in most patients, with a range from 338 of 438 (77.2%) in patients with LDL-C levels of ≥190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of ≥77 mg/dL.

Further, the team observed in all LDL-C groups, the 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 - 99 (11.1; 95% CI, 10.0 - 12.5 per 1000 person-years) and CAC scores of ≥100 (21.9; 95% CI, 19.9 - 24.4 per 1000 person-years).

The event rate per 1000 person-years in those with CAC scores of 0 was 6.3 (95% CI, 5.6 - 7.0) in the overall population, compared to 6.9 (95% CI, 4.0 - 11.9) in those with LDL-C levels of ≥190 mg/dL.

“These findings demonstrate that a number of additional factors beyond elevated LDL-C levels affect atherogenesis in the individual patient, despite LDL-C level being the pathophysiological causal agent in atherogenesis,” Mortensen concluded.

The study, “Association of Coronary Plaque With Low-Density Lipoprotein Cholesterol Levels and Rates of Cardiovascular Disease Events Among Symptomatic Adults,” was published in JAMA Network Open.