"LDL cholesterol is the main lipid measurement to guide clinical decisions," Dr. John Burnett of Royal Perth Hospital and Fiona Stanley Hospital Network told Reuters Health by email. "However, residual risk of atherosclerotic cardiovascular disease (ASCVD) remains even after LDL cholesterol is treated."
"Triglycerides (TG) and/or the cholesterol content within TG-rich lipoproteins may contribute to residual lipid-related ASCVD risk," said Dr. Burnett, coauthor of an editorial commenting on both studies.
In one study, Dr. Borge Nordestgaard of Copenhagen University Hospital and colleagues analyzed records of more than 25,000 individuals in the Copenhagen General Population Study (CPGS) to see whether VLDL cholesterol and triglycerides each explain part of the myocardial infarction (MI) risk from plasma apolipoprotein B (apoB)-containing lipoproteins that cause ASCVD.
Multivariable-adjusted hazard ratios for MI per 1-mmol/L higher levels were 2.07 for VLDL cholesterol, 1.19 for VLDL triglycerides, 5.38 for intermediate-density lipoprotein (IDL) cholesterol, and 1.86 for LDL cholesterol.
In a step-up Cox regression, risk factors for MI (in order of importance) were VLDL cholesterol, systolic blood pressure, smoking, and IDL plus LDL cholesterol. VLDL triglycerides did not enter the model.
"The take-home message is that VLDL cholesterol explained one-half of the myocardial infarction risk from elevated apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk," Dr. Nordestgaard said.
"Also, VLDL cholesterol explained more of the MI risk from elevated apoB than LDL cholesterol," he noted. "These data underscore the importance of targeting VLDL cholesterol, which should be discussed with patients having elevated plasma triglycerides."
"Future work includes the role of VLDL cholesterol in explaining part of the excess risk of MI in individuals with obesity," he added. "This is important, as elevated VLDL cholesterol is particularly prevalent in the obese."
In the second study, Dr. Montserrat Fito of Hospital del Mar Medical Research Institute in Barcelona and colleagues studied the association of TG and remnant cholesterol with major adverse cardiovascular events (MACEs) in the high-risk primary prevention PREDIMED trial population after a median follow-up of 4.8 years (mean age, 67; 43% men, of whom 48% had diabetes; mean BMI, 30 kg/m2).
In multivariable-adjusted analyses, TG (hazard ratio,1.04), non-high-density lipoprotein (HDL) cholesterol (HR, 1.05), and remnant cholesterol (HR, 1.21), but not LDL or HDL cholesterol, were associated with MACEs.
Atherogenic dyslipidemia (triglycerides >150 mg/dl and HDL <40 mg/dl in men or <50 mg/dl in women) was also associated with MACEs (HR: 1.44).
Notably, remnant cholesterol at 30 mg/dl or greater differentiated participants at a higher risk of MACEs compared with those at lower concentrations, regardless of whether LDL levels were on target at 100 mg/dl or less.
Editorialist Dr. Burnett noted that under different experimental designs and analytical methods, CGPS and PREDIMED "both showed significant atherosclerotic risk attributable to cholesterol within TG-rich lipoproteins and remnant particles. Assessment of residual ASCVD risk with non-traditional lipid biomarkers, including VLDL cholesterol and remnant cholesterol as well as lipoprotein (a) and apolipoprotein (apo)B may improve prognostication and help guide preventive treatments."
"Recent European consensus-based recommendations give the option of calculating remnant cholesterol from a traditional lipid profile, as was done in the PREDIMED study," he said. "However, remnant cholesterol, like Lp(a) and apoB, is not currently part of ASCVD risk estimation models."
"NMR spectroscopy, as used in the CGPS, while promising, is relatively new, expensive, not widely available and needs to be further field tested and validated," he said.
"In contrast to LDL-cholesterol, evidence from clinical intervention trials is lacking for remnant lipoproteins," he added. "At least four or five more years of work are needed, particularly clinical trials in which these new lipid markers are intentionally included in entry criteria, are specifically targeted and the outcomes are followed."
Dr. Fito did not respond to a request for a comment.
SOURCE: https://bit.ly/3lqyxVM, https://bit.ly/3lxe2Hn and https://bit.ly/2Jqdtl8 Journal of the American College of Cardiology, online November 30, 2020.
By Marilynn Larkin
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