Christie M. Ballantyne
Triglycerides in LDL predicted CVD events and were associated with a genetic variant, according to new findings.
The researchers assessed whether triglycerides in LDL (LDL-TG) and remnant-like particle cholesterol (RLP-C) were associated with incident CVD and genetic variants in 9,334 participants (5,527 women) from the ARIC study without CVD at baseline.
“A lot of information we have gathered over the years has indicated that high triglyceride levels increase the risk for cardiovascular disease. Since triglycerides and cholesterol are carried through the bloodstream in multiple particles known as lipoproteins, our focus was to take a closer look at the levels in those particles and how they affect outcomes,” Christie M. Ballantyne, MD, professor of medicine and chief of the sections of cardiology and cardiovascular research at Baylor College of Medicine, said in a press release.
Participants were followed for incident CHD or ischemic stroke for up to 16 years.
The researchers conducted whole-exome sequencing using single-variant analysis for common variants and gene-based burden tests for rare variants to determine associations between variants and LDL-TG or RLP-C.
According to the researchers, LDL-TG (r = 0.64; P < .0001) and RLP-C (r = 0.85; P < .0001) correlated with triglyceride levels.
After minimal adjustment, LDL-TG and RLP-C were associated with elevated CVD risk, but after further adjustment for traditional risk factors including lipids, LDL-TG was associated with increased risk for CHD (HR = 1.28; 95% CI, 1.1-1.5) and ischemic stroke (HR = 1.47; 95% CI, 1.13-1.92), but RLP-C was not.
“Usually lipid measurements are not associated with risk for stroke, so this is the first time we are seeing LDL-TG have a positive association on predicting the risk of both heart attack and stroke,” Anum Saeed, MD, a clinical postdoctoral fellow in cardiovascular disease prevention (lipids and atherosclerosis) at Baylor and also with the Center for Cardiometabolic Disease Prevention, said in the release. “This was a new finding; we normally don’t check these levels, but our results are showing us that this appears to be the best predictor of heart attack and stroke.”
The variant with the strongest association with LDL-TG and RLP-C was the rs7412 variant of APOE, also known as APOE2, (P < 5 x 10-8), Ballantyne and colleagues wrote.
“We already know that APOE2 is associated with lower risk of cardiovascular disease; thus, the lower level of LDL-TG observed in these individuals suggests that reduced LDL-TG may play an important role in protection from cardiovascular disease,” Ballantyne said in the release.
“We know that there is an emerging problem of obesity and diabetes and the risk profile has changed for many populations, so we are in need of a more accurate way to predict cardiovascular disease. These findings are pointing to a new way to assess risk but also to a potential treatment target,” Saeed said in the release. “Our next step will be to see how lifestyle modifications or medications affect LDL-TG levels and if that affects outcomes of cardiovascular disease.”
Randomized trials needed
“To advance LDL-TG as a potential target of therapy, it will be important to validate its role as an independent predictor of CVD in randomized controlled trials,” Michael Miller, MD, from the division of cardiovascular medicine, department of medicine, University of Maryland School of Medicine, wrote in a related editorial. “To date however, the sole randomized controlled trial to report LDL-TG, AIM-HIGH, did not identify LDL-TG as a significant predictor of CVD events. Fortunately, several ongoing randomized controlled trials provide such an opportunity, and positive results may help further solidify a role for LDL-TG in the atherogenic landscape beyond non-high-density lipoprotein cholesterol, apolipoprotein B and other conventional measures.” – by Erik Swain
Disclosures: Ballantyne and Saeed report no relevant financial disclosures. One author reports he received a research grant from Denka Seiken.