News | November 04, 2014

Genetic Predisposition to Elevated LDL-C Linked to Aortic Valve Stenosis

The study is being released to coincide with its presentation at the Canadian Cardiovascular Congress

aortic stenosis, Canadian Cardiovascular Conference, LDL-C

Nov. 4, 2014 — In an analysis that included approximately 35,000 participants, genetic predisposition to elevated low-density lipoprotein cholesterol (LDL-C) was associated with aortic valve calcium and narrowing of the aortic valve, findings that support a causal association between LDL-C and aortic valve disease, according to a study appearing in JAMA. The study is being released to coincide with its presentation at the Canadian Cardiovascular Congress.

Aortic valve disease remains the most common form of heart valve disease in Europe and North America and is the most common indication for valve replacement. Despite the heavy disease burden, no medical treatments are known to stop or slow disease progression. Plasma LDL-C has been associated with aortic in observational studies. Randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression. If LDL-C plays a causal role in the earlier stages of aortic valve disease, this could have important implications for prevention, according to background information on the article.

Because of the random allocation of genetic information that occurs at conception, genetic variation can be used as an effective tool to distinguish potentially causal from noncausal biomarkers. Termed "Mendelian randomization," this approach has been successfully applied to assess for causality of several biomarkers with various clinical end points. Using this approach, J. Gustav Smith, M.D., of Lund University, Lund, Sweden, and colleagues, evaluated whether weighted genetic risk, a measure of the genetic predisposition to elevations in plasma lipids, were associated with aortic valve disease. The researchers included community-based cohorts participating in the CHARGE consortium (n = 6,942), including the Framingham Heart Study (cohort inception to last follow-up: 1971-2013; n = 1,295), Multi-Ethnic Study of Atherosclerosis (2000-2012; n = 2,527), Age Gene/Environment Study–Reykjavik (2000-2012; n = 3,120), and the Malmö Diet and Cancer Study (MDCS, 1991-2010; n = 28,461). Aortic valve calcium was quantified by computed tomography; prevalent and new diagnoses of aortic stenosis and aortic valve replacement were identified by record linkage with nationwide registers on hospitalizations and causes of death. 

The researchers found that in the subgroup of the MDCS where lipid fractions were measured (n = 5,269), baseline LDL-C, but not HDL-C or TG levels, was significantly associated with new aortic stenosis. Also, the LDL-C GRS, but not HDL-C or TG GRS, was significantly associated with presence of aortic valve calcium in CHARGE and with new aortic stenosis in MDCS.

"Our findings link a genetically mediated increase in plasma LDL-C with early subclinical valve disease, as measured by aortic valve calcium, and incident clinical aortic stenosis, providing supportive evidence for a causal role of LDL-C in the development of aortic stenosis," the authors write. "These data suggest that, in addition to the established risks for myocardial infarction and other vascular diseases, increases in LDL-C are also associated with increased risk for aortic stenosis."

"Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation."

Related Content

New Best Practices Help Manage Heart Attack Patients Without Significant Signs
News | Cardiac Diagnostics | April 15, 2019
For the first time in the United States, doctors with the American Heart Association (AHA) have outlined best practices...
The most recent U.S. Food and Drug Administration (FDA) clearance was Siemens Healthineers high-sensitivity troponin I assays (TnIH) for the Atellica IM and ADVIA Centaur XP/XPT in vitro diagnostic analyzers. The test helps in the early diagnosis of myocardial infarctions without the need for serial tropic testing. The time to first results is 10 minutes.

The most recent U.S. Food and Drug Administration (FDA) clearance was Siemens Healthineers high-sensitivity troponin I assays (TnIH) for the Atellica IM and ADVIA Centaur XP/XPT in vitro diagnostic analyzers. The test helps in the early diagnosis of myocardial infarctions without the need for serial tropic testing. The time to first results is 10 minutes. 

Feature | Cardiac Diagnostics | March 22, 2019 | Linda C. Rogers, Ph.D.
Troponins are a family of proteins found in skeletal and heart (cardiac) muscle fibers that produce muscular contract
ACC/AHA Update Guidance for Preventing Heart Disease; Stroke
Feature | Cardiac Diagnostics | March 18, 2019
The choices we make every day can have a lasting effect on our heart and vascular health. Adopting a heart healthy...
AHA Statement Warns Hookah Smoking May Harm the Heart
News | Cardiac Diagnostics | March 08, 2019
Smoking tobacco in waterpipes, more commonly known as hookahs, results in inhaling toxic chemicals, often at levels...
PTSD Alone Does Not Increase Heart Disease Risk in Veterans
News | Cardiac Diagnostics | February 20, 2019
February 20, 2019 — Post-traumatic stress disorder (PTSD) by itself does not explain the...
Hormone Therapy May Increase Cardiovascular Risk During Gender Transition
News | Cardiac Diagnostics | February 18, 2019
Patients receiving hormone therapy as part of their gender-transition treatment had an elevated risk for cardiovascular...
IBM and Broad Institute Launch AI Initiative for Cardiovascular Disease Risk Prediction
News | Cardiac Diagnostics | February 15, 2019
IBM Watson Health and the Broad Institute of MIT and Harvard are launching a research partnership aimed at developing...
Nearly Half of All U.S. Adults Have Cardiovascular Disease
News | Cardiac Diagnostics | January 31, 2019
January 31, 2019 — Nearly half (48 percent, 121.5 million in 2016) of all adults in the United States have some type
Frequent Red Meat Consumption Triples Levels of Chemical Associated With Heart Disease
News | Cardiac Diagnostics | January 23, 2019
Researchers have identified another reason to limit red meat consumption: high levels of a gut-generated chemical...
Overlay Init