This article is more than 5 years old. Information may no longer be current.
Two genetic variants may reduce CV event risk, increase diabetes risk
Click Here to Manage Email Alerts
Variants of the PCSK9 and HMGCR genes linked to lower LDL were associated with protection from CV events and increased risk for diabetes in certain populations, according to findings published in The New England Journal of Medicine.
The researchers compared the effects of lower LDL levels conferred by the variants of PCSK9 and HMGCR on risk for CV events and diabetes. They wrote that PCSK9 variants mimic the effects of PCSK9 inhibitors, and the HMGCR variants mimic the effects of statins.
Brian A. Ference, MD, and colleagues stratified 112,772 participants (weighted mean age, 60 years) from 14 studies by genetic score composed of seven independently inherited variants of the PCSK9 gene and six independently inherited variants of the HMGCR gene known to confer lower LDL. Among the study population, there were 14,120 CV events and 10,635 cases of diabetes.
The researchers compared those with a genetic score above the median with those with a score below the median.
Ference, from the division of cardiovascular medicine, Wayne State University School of Medicine, Detroit, and colleagues found the PCSK9 variants had protective effects on the risk for CV events (OR per LDL decrease of 10 mg/dL = 0.81; 95% CI, 0.74-0.89), as did the HMGCR variants (OR per LDL decrease of 10 mg/dL = 0.81; 95% CI, 0.72-0.9).
However, the PCSK9 variants were associated with an increase in risk for diabetes (OR per LDL decrease of 10 mg/dL = 1.11; 95% CI, 1.04-1.19), as were the HMGCR variants (OR per LDL decrease of 10 mg/dL = 1.13; 95% CI, 1.06-1.2), according to the researchers.
The researchers wrote that for both sets of variants, the increased risk for diabetes was limited to individuals who had impaired fasting glucose levels, and was not as strong as the protective effect for CV events.
“We found that genetic variants that mimic the effect of PCSK9 inhibitors had remarkably similar effects on the risk [for CV] events and the risk of diabetes as compared with variants that mimic the effect of statins when measured per unit change in the LDL level,” Ference and colleagues wrote. “Furthermore, we found that when variants that mimic the effect of PCSK9 inhibitors and statins were present together, they had independent and additive effects on the risk of both [CV] events and diabetes.”
Marc S. Sabatine, MD, MPH, chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group and the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, said in a press release that “Our findings suggest that treatment with a PCSK9 inhibitor, used either alone or in combination with a statin, should reduce the risk [for CV] events to the same degree as do statins per unit reduction in LDL.” – by Erik Swain
Disclosure: Ference reports receiving grant support and personal fees from Amgen, Esperion and Merck, and receiving personal fees from Ionis. Please see the full study for a list of the other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts