This article is more than 5 years old. Information may no longer be current.
Reduction in apoB particles may play key role in benefit from LDL lowering
Click Here to Manage Email Alerts
Drop in risk for CV events corresponded more closely with reduction in apolipoprotein B levels than with reduction in LDL levels, according to a Mendelian randomization study published in JAMA.
“The clinical benefit of lowering LDL levels may therefore depend on the corresponding reduction in apoB-containing lipoprotein particles,” Brian A. Ference, MD, MPhil, MSc, from the division of cardiovascular medicine at Wayne State University School of Medicine, Detroit, and colleagues wrote.
Ference and colleagues undertook the study to estimate the association between changes in levels of LDL and other lipoprotein levels and risk for CV events related to variants in the CETP gene alone or in conjunction with variants in the HMGCR gene.
They conducted Mendelian randomization analyses for 102,837 individuals (mean age, 60 years; 58% women) from 14 cohort or case-control studies conducted between 1948 and 2012, and validated the findings in 189,539 individuals (mean age, 59 years; 39% women) from 48 studies conducted between 2011 and 2015.
LDL and apoB
In the primary cohort, there were 13,821 major CV events, and in the validation cohort, 62,240 people developed CHD, the researchers wrote.
CETP score was associated with higher levels of HDL, lower levels of LDL, lower levels of apoB and lower risk for major vascular events (OR = 0.946; 95% CI, 0.921-0.972), similar in magnitude to the link between HMGCR score and risk for major CV events per unit change in levels of LDL and apoB, Ference and colleagues wrote.
When the CETP score was combined with HMGCR score, its association with reduction in LDL levels did not change but its association with reduction in apoB levels was attenuated, as was its association with risk for major CV events (OR = 0.985; 95% CI, 0.955-1.015), the researchers wrote.
In the validation cohort, compared with a genetic score associated with concordant changes in levels of LDL and apoB, a genetic score consisting of variants associated with discordant levels of LDL and apoB was associated with similarly reduced risk for CHD per unit change in apoB (OR = 0.782; 95% CI, 0.793 vs. OR = 0.793; 95% CI, 0.774-0.812; P for difference = .79) but attenuated risk for CHD per unit change in LDL level (OR = 0.916; 95% CI, 0.89-0.943 vs. OR = 0.831; 95% CI, 0.816-0.847; P for difference < .001), according to the researchers.
ApoB confers risk
“These genetic studies were consistent not only with results of the CETP inhibitor trials but also with several prior epidemiologic discordance analyses, which demonstrated that when the LDL level is high but the apoB level is low, [CV] risk is low. By contrast, when the LDL level is low but the apoB level is high, [CV] risk is high,” Allan D. Sniderman, MD, FRCP(C), FRSC, from the department of medicine/cardiology at McGill University, Montreal, and Eric D. Peterson, MD, from Duke University Medical Center, wrote in a related editorial.
“Clinicians could consider the utility of apoB levels as the primary target of lipid lowering rather than LDL levels,” they wrote. “The logical next step is to reframe the lipid hypothesis as the lipoprotein particle hypothesis.”
The findings were also presented at the European Society of Cardiology Congress. – by Erik Swain
Disclosures: Ference reports he receives personal fees from Amgen, Ionis, KrKA and Merck, and grants from Amgen, Esperion and Merck. Please see the full study for a list of the other authors’ relevant financial disclosures. Peterson reports he receives grants from Amgen and grants and personal fees from AstraZeneca, Merck and Sanofi Aventis. Sniderman reports he has no relevant financial disclosures.
Click Here to Manage Email Alerts