In a large study of symptomatic adults with LDL-C of at least 190 mg/dL, the absence of CAC and noncalcified plaque was associated with a low risk of myocardial infarction, stroke and death over about four years.
The findings suggest that "atherosclerosis burden, including assessment of CAC, can be used to individualize treatment intensity by identifying patients who are at low risk despite having severely elevated LDL-C levels," Dr. Martin Boedtker Mortensen with Aarhus University Hospital in Denmark and colleagues write in JAMA Network Open.
U.S. and European guidelines recommend statins for all patients with severe hypercholesterolemia (LDL-C higher than 190 mg/dL) to prevent ASCVD. But some studies have suggested that a "sizeable" proportion of these patients are resilient to developing calcified coronary plaque, suggesting the possibility of more tailored treatment.
Dr. Mortensen and colleagues studied more than 23,000 symptomatic patients who underwent coronary CT angiography (CCTA) between 2008 and 2017.
They determined the 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 190 mg/dL or higher. The severity of coronary-artery disease was categorized using CAC scores of 0, 1 to 99, and 100+, with higher numbers indicating greater CAC burden.
During mean follow-up of 4.2 years, 1,029 ASCVD events and deaths occurred.
The researchers say four key points emerge from their analyses.
First, atherosclerotic burden is "heterogeneous" across the spectrum of LDL-C levels, and risk is consistently associated with plaque burden.
Second, the absence of plaque was a prevalent finding, seen in 46.2% of patients with LDL-C levels of at least 190 mg/dL and similar to that in patients with lower LDL-C levels.
Third, CAC determined by CCTA indicated no detectable plaque in 86.8% of patients, including those with LDL-C levels above 190 mg/dL, although the prevalence of noncalcified plaque increased with higher LDL-C levels.
Fourth, absence of plaque and CAC was associated with low ASCVD event rates across the LDL-C spectrum, even when nonobstructive noncalcified plaques were present. "Notably, however, when noncalcified obstructive coronary artery disease was present, event rates were high, demonstrating that CAC scores of 0 miss a small proportion of individuals at high risk," they say.
"Taken together, our results support the use of CCTA results for risk stratification (including derisking) of symptomatic patients with high LDL-C levels," Dr. Mortensen and colleagues say.
"This is important because such individuals are universally considered to be at high risk with very low LDL-C goals that can only be achieved by treatment with statins in combination with novel therapies to lower lipid levels. Among the large proportion of patients with LDL-C levels of at least 190 mg/dL who have no atherosclerotic plaque, the net benefit of such intensive treatment is questionable," they add.
This study extends the apparent "safety bubble" when CAC or plaque is absent to people with severe hypercholesterolemia and possible symptoms of coronary-artery disease, says the author of a linked editorial in JAMA Network Open.
Dr. Raul Santos of the Heart Institute University of Sao Paulo Medical School Hospital, in Brazil, notes that two other studies with about three years' follow-up found "a very low risk of ASCVD events in asymptomatic individuals with proven genetic diagnosis of familial hypercholesterolemia and CAC scores of 0, although most of them were using statins."
Importantly, "absence of CAC or plaques does not mean that people with severe hypercholesterolemia should not receive statin therapy as recommended by guidelines, especially in young individuals; however, imaging may help to guide use of effective and safe, but high-cost, proprotein convertase subtilisin/kexin type 9 inhibitors for those who still have inadequate LDL-C values," Dr. Santos writes.
"It is hoped that longer follow-ups of people with severe hypercholesterolemia and absence of CAC or plaques will confirm study findings and help improve stratification and guide more aggressive LDL-C level-lowering therapies, even in this so-called high-risk group," he concludes.
The study had no specific funding. Dr. Mortensen has no relevant disclosures.
SOURCE: https://bit.ly/3uXxvJi and https://bit.ly/33s1DkM JAMA Network Open, online February 11, 2022.
By Reuters Staff
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