This article is more than 5 years old. Information may no longer be current.
Lifetime genetic exposure to low LDL, BP impacts CV risk
Click Here to Manage Email Alerts
PARIS — Lifetime genetic exposure to lower systolic BP and lower LDL levels was linked with lower CV risk, according to data presented at the European Society of Cardiology Congress.
“These large proportional reductions in [CVD] risk with relatively small decreases in exposure to LDL and blood pressure suggest that both for LDL, systolic BP and the combination [of LDL and systolic BP], that benefit really depends on both the magnitude and duration of exposure,” Brian A. Ference, MD, MPhil, MSc, FACC, FESC, director of research (professor) in translational therapeutics and executive director of the Center for Naturally Randomized Trials at the University of Cambridge, U.K., said during a press conference.
Ference and colleagues analyzed data from 438,952 adults (mean age, 65 years; 54% women) enrolled in the UK Biobank. The researchers used 100 exome variants associated with LDL and 61 exome variants associated with systolic BP to construct genetic scores. Weighted genetics LDL and systolic BP scores were also calculated.
“Ideally we’d like to evaluate the effect of long-term exposure to both LDL lowering and systolic BP in a long-term randomized trial, but that trial would take several decades to complete, so it’s unlikely to occur,” Ference said here. “Instead, we used genetic variants associated with lower LDL and systolic BP to conduct a ‘naturally randomized’ trial. Specifically, the way we did that was we randomized people to higher and lower LDL based on their genetic risk score then re-randomized them to higher or lower systolic blood pressure, creating four groups: a reference group, a group of lifetime exposure to lower LDL, a group of lifetime exposure to systolic blood pressure and a group of lifetime exposure to both.”
A total of 24,980 participants had a first major coronary event.
The main outcome was the odds ratio for major coronary events, which the researchers defined as a composite of nonfatal MI, coronary death or coronary revascularization. The main outcome results presented here were as follows:
- those with LDL genetic scores greater than the median had 14.7 mg/dL lower levels of LDL compared with the reference group: OR = 0.73 (95% CI, 0.7-0.75);
- those with systolic BP genetic scores greater than the median had 2.9 mm Hg lower levels of systolic BP compared with the reference group: OR = 0.82 (95% CI, 0.79-0.85); and
- those with both genetic scores higher than the median had 3.1 mm Hg lower levels of systolic BP and 13.9 mg/dL lower levels of LDL compared with the reference group: OR = 0.61 (95% CI, 0.59-0.64).
Ference and colleagues also performed a 4x4 factorial analysis, which revealed that increases in genetic scores and lower levels of LDL and systolic BP were linked with a dose-dependent lower risk for major coronary events.
Combined exposure to 10-mm Hg lower systolic BP and 38.67-mg/dL lower LDL was associated with a 68% lower lifetime risk for CV death (OR = 0.32; 95% CI, 0.25-0.4) and an 80% lower lifetime risk for CVD (OR = 0.22; 95% CI, 0.17-0.26), Ference said during the Hot Line Session presentation.
“Most importantly, this confirms the notion that most cardiovascular events are preventable, and it suggests that most cardiovascular events can be prevented with prolonged exposure to the combination of both lower LDL and lower systolic blood pressure,” Ference said during the press conference. – by Darlene Dobkowski
References:
Ference BA. Hot Line 3. Presented at: European Society of Cardiology Congress; Aug. 31-Sept. 4, 2019; Paris.
Ference BA, et al. JAMA. 2019;doi:10.1001/jama.2019.14120.
Disclosures: Ference reports he receives grants from Afimmune, Amgen, Esperion Therapeutics, Merck & Co., Novartis and Regeneron and personal fees from American College of Cardiology, Amgen, CiVi Pharma, dalCOR, Eli Lilly, European Atherosclerosis Society, European Society of Cardiology, Integral Therapeutics, Ionis Pharmaceuticals, KrKa Pharmaceuticals, Merck & Co., Mylan, Novo Nordisk, Pfizer, Regeneron, Sanofi, Silence Therapeutics and The Medicine Company. Please see the study for all other authors’ relevant financial disclosures.
Perspective
Back to Top
Natasja M.S. de Groot, MD, PhD
This is a very interesting study in a way that you can see that the reduction of CV risk factors has such an important impact. We tend to forget that and apply complex therapies for CV diseases. This is just a simple thing that can also be taken care of by primary care physicians. This is very important.
Click Here to Manage Email Alerts