Do mutations causing low HDL-C promote increased carotid intima-media thickness?
Michael Miller1, Jeffrey Rhyne, Seung Ho Hong
1University of Maryland Hospital and Veterans Affairs Medical Center, Baltimore, MD 21201, United States. mmiller@medicine.umaryland.edu
Clinica Chimica Acta; International Journal of Clinical Chemistry
|November 23, 2006
Summary
Genetic mutations causing low high-density lipoprotein (HDL) cholesterol did not lead to early atherosclerosis in this study. Low HDL cholesterol and apolipoprotein A-I levels did not correlate with increased carotid intima-media thickness.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Biochemistry
Background:
- Observational studies suggest a link between high-density lipoprotein (HDL) cholesterol and reduced coronary heart disease (CHD) risk.
- However, individuals with genetic HDL deficiency often do not experience premature CHD, challenging this association.
- This discrepancy highlights the need to investigate the direct impact of genetic HDL variations on atherosclerosis.
Purpose of the Study:
- To investigate the relationship between genetically determined low high-density lipoprotein (HDL) cholesterol and early atherosclerosis.
- To evaluate carotid intima-media thickness (cIMT) in individuals with mutations affecting HDL metabolism.
- To determine if genetic HDL deficiency directly promotes the development of early carotid atherosclerosis.
Main Methods:
- A case-control study was conducted involving 114 subjects, with a 1:2 ratio of cases to controls.
- Cases included individuals with 10 distinct mutations in LCAT, ABCA1, and APOA1 genes, impacting HDL levels.
- Carotid intima-media thickness (cIMT) was measured and compared between cases and controls, matched for sex and age.
Main Results:
- Despite significantly lower HDL cholesterol and apolipoprotein A-I levels in cases compared to controls (P<0.05), cIMT measurements were nearly identical.
- The mean cIMT was 0.66+/-0.17 cm in cases versus 0.65+/-0.18 cm in controls.
- These findings indicate no significant difference in early atherosclerosis markers between individuals with genetic HDL deficiency and controls.
Conclusions:
- The genetic variants studied, leading to low HDL cholesterol, appear insufficient to promote early carotid atherosclerosis.
- This suggests that factors beyond HDL cholesterol levels, influenced by these specific genetic mutations, may be more critical in the development of atherosclerosis.
- Further research is needed to fully elucidate the complex interplay between genetic factors, HDL, and cardiovascular disease risk.
Related Concept Videos
01:30Coronary Artery Disease I: Introduction
Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
01:26Atherosclerosis III: Management
Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
01:30Atherosclerosis I: Introduction
Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
01:26Coronary Artery Disease II: Pathophysiology
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
01:26Coronary Artery Disease IV: Preventive Measures
Effective preventive measures for coronary artery disease (CAD) focus on controlling modifiable risk factors, including cholesterol abnormalities and lifestyle changes.Cholesterol ManagementFirst, the Mediterranean diet and the American Heart Association advocate for maintaining low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL, with a more stringent recommendation of below 70 mg/dL for individuals at high risk. LDL cholesterol, often termed "bad cholesterol," can lead to the...