Genetically high LDL-C may increase risk for aortic valve disease

According to a multinational study, genetically high levels of low-density lipoprotein cholesterol (LDL-C) may put patients at increased risk for aortic valve disease. No similar association was found between high-density lipoprotein cholesterol (HDL-C) or triglycerides and the development of aortic valve calcium and stenosis.

The authors hoped findings from the study published online Oct. 26 in JAMA would improve LDL-C reduction interventions to determine if better control would prevent aortic valve disease.

Patients from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium—which includes the Framingham Heart, MESA (Multi-ethnic Study on Atherosclerosis), AGES (Age, Gene/Environment Susceptibility – Reykjavik) and  Malmö Diet and Cancer Study—were tapped for this Mendelian randomized investigation. J. Gustav Smith, MD, from the cardiology department at Lund University in Lund, Sweden, and colleagues evaluated genetic data, CT images and, in the case of the Malmö data, diagnosed stenosis through a national registry. Patients were largely of European descent.

Genome-wide association study summary-level data were used in evaluating the CHARGE cohorts, while direct genotype-phenotype data were analyzed in the Malmö cohort. In both groups, they used single-nucleotide polymorphisms to determine whether patient cholesterol was weighted toward high LDL-C, HDL-C, or triglycerides.

In keeping with observations made in prior studies on high risk of stenosis due to familial hypercholesterolemia and high levels of LDL-C, Smith et al found a link between patients with genetically high predisposition to LDL-C and both aortic valve calcium and aortic stenosis. They found risk for aortic stenosis with elevated LDL-C increased per mmol/L (hazard ratio 1.28) over recommended levels. Patients with LDL-C dominant genetic risk scores had one-third greater risk of aortic valve calcium on imaging. Stenosis incidence was nearly tripled in in patients with LDL-C dominant genetic risk scores (hazard ratio: 2.78).

Smith et al noted that these findings strongly suggest that the mechanism for increased LDL-C was “likely responsible for the association with aortic valve disease” as opposed to HDL-C or triglycerides. They wrote that early intervention in patients with high LDL-C levels, particularly due to genetics, may offer protection for these patients against developing the calcification and stenosis associated with aortic valve disease.

While some randomized trials suggested that changes to LDL-C through statin therapy would not affect aortic valve disease progression, Smith et al noted patients in those studies were older with established valve disease. “Once valve calcification and remodeling are well established, factors other than LDL-C, including hemodynamic forces and other procalcifying mediators, may become more important for progression,” they wrote, emphasizing the need to tackle LDL-C levels early to improve patient outcomes.

Around the web

Eleven medical societies have signed on to a consensus statement aimed at standardizing imaging for suspected cardiovascular infections.

Kate Hanneman, MD, explains why many vendors and hospitals want to lower radiology's impact on the environment. "Taking steps to reduce the carbon footprint in healthcare isn’t just an opportunity," she said. "It’s also a responsibility."

Philips introduced a new CT system at ECR aimed at the rapidly growing cardiac CT market, incorporating numerous AI features to optimize workflow and image quality.

Trimed Popup
Trimed Popup