"Guidelines today in my opinion overemphasize LDL cholesterol, making clinicians ignore other causal lipoproteins for atherosclerotic cardiovascular disease, including triglyceride-rich lipoproteins," Dr. Borge Gronne Nordestgaard of Copenhagen University Hospital told Reuters Health by email.
"To better understand residual cardiovascular risk in statin-treated patients," he said, "we compared head-to-head the value of high LDL cholesterol versus high apoB and high non-HDL cholesterol, both of which capture LDL and triglyceride-rich lipoproteins combined."
The findings should be considered practice-changing, he said. "In any patient at increased cardiovascular risk, look at all of LDL cholesterol, apoB, and non-HDL cholesterol to better decide the next step for further reduction of cardiovascular risk. If apoB is not available, always look at both LDL and non-HDL cholesterol."
As reported in the Journal of the American College of Cardiology, more than 13,000 statin-treated patients (median age, about 68; 37%-58% women, depending on ApoB and cholesterol values; all White) from the Copenhagen General Population Study were included, with a median of eight years follow-up.
Cox regression analyses showed that high apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction; no such associations were found for high LDL cholesterol.
Discordance analyses revealed that discordant apoB above the median with LDL cholesterol below showed an HR of 1.21 for all-cause mortality, compared with concordant apoB and LDL cholesterol below the medians. Similar results were found for discordant non-HDL cholesterol above the median with LDL cholesterol below (HR: 1.18).
By contrast, discordant high LDL cholesterol with either low apoB or low non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Further, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 for all-cause mortality and 0.93 for myocardial infarction.
Notably, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below yielded hazard ratios of 1.23 for all-cause mortality and 1.82 for myocardial infarction.
Summing up, the authors state, "In statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk...than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol."
Dr. Nordestgaard said the team's next research steps will include "looking at relative importance of elevated LDL cholesterol versus elevated remnant cholesterol (triglyceride-rich lipoprotein cholesterol) for increased cardiovascular risk in patients with and without statin use."
Dr. Neil Stone of the Feinberg School of Medicine, Northwestern University in Chicago, coauthor of a related editorial, commented in an email to Reuters Health, "These new observations add to the growing literature showing that there are patients with statin-treated levels of LDL cholesterol that are below the average level, but who still have elevated markers such as non-HDL-C or apo B."
"This is likely, for example, in patients with elevated triglycerides and metabolic disorders such as obesity, insulin resistance, metabolic syndrome or diabetes," he said. "Our editorial notes that for those with increased non-HDL-C/apoB after statin therapy, improvements in diet, weight and increased activity may help lower these numbers and attendant risk. The focus is not only on more drug therapy."
"Another implication of the (study) is that sequential use, rather than routine use, of non-HDL-C or apoB still makes sense," he added. "Starting with statins in high-risk patients is important and backed by a wealth of data."
"In situations where statin use is suboptimal, maximizing statin intensity would appear to be the most important first step in reducing residual risk, and then it may be important to consider how measurement of apoB and non-HDL-C could influence guideline-directed care," Dr. Stone concluded.
SOURCES: https://bit.ly/3eMLHNq and https://bit.ly/3s78sQ5 Journal of the American College of Cardiology, online March 15, 2021.
By Marilynn Larkin
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