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Familial hypoalphalipoproteinemia in premature coronary artery disease
J Genest1, J M Bard, J C Fruchart
1Lipid Metabolism Laboratory, Tufts University, Boston, Mass. 02111.
Insights
Familial hypoalphalipoproteinemia (HA) is linked to premature heart disease. Common forms involve increased apoB lipoproteins and smaller, denser LDL particles, affecting about half of offspring.
Area of Science:
- Cardiovascular Genetics
- Lipid Metabolism Disorders
- Atherosclerosis Research
Background:
- Hypoalphalipoproteinemia (HA) is frequently observed in individuals with premature coronary artery disease.
- Understanding the common familial forms of HA is crucial for risk stratification and management.
Observation:
- This study investigated 102 families with probands exhibiting premature coronary artery disease, identifying HA in 39.2%.
- Familial forms included familial hypertriglyceridemia with HA (FTgHA), familial combined hyperlipidemia (FCH), and familial HA (FHA).
- Measurements included apolipoproteins (apoA-I, B, C-III, E) and lipoprotein particles (LpA-I, LpA-I:A-II, LpB:E, LpB:C-III).
Findings:
- Familial HA forms showed decreased apoA-I and lower LpA-I/LpA-I:A-II levels compared to healthy controls.
- All familial HA groups exhibited significantly higher apoB levels, with the highest in FCH.
- Smaller, denser LDL particles were noted in all familial HA forms, indicating an increased number of atherogenic LDL particles.
Implications:
- Common familial HA forms associated with coronary artery disease represent a spectrum of disorders.
- Elevated apoB-containing lipoproteins, particularly LpB:E particles and small, dense LDL, are key characteristics.
- Approximately half of the offspring in affected families may inherit these lipoprotein abnormalities.
Abstract:
Hypoalphalipoproteinemia (HA) is a common finding in patients with premature coronary artery disease. To characterize the common familial forms of HA, we studied 102 families of probands with premature coronary artery disease; 40 probands (39.2%) had HA. Of these, 25 had at least one first-degree relative affected with HA; 11 had familial hypertriglyceridemia with HA (FTgHA); 10 had familial combined hyperlipidemia (FCH); and 4 had familial HA (FHA) with no other lipoprotein abnormalities. In the remaining 15 families, no lipoprotein abnormalities were observed in first-degree relatives. We measured apolipoprotein (apo) A-I, B, C-III, and E levels as well as lipoprotein particle (Lp) levels of LpA-I (containing apoA-I only), LpA-I:A-II (containing both apoA-I and A-II), LpB:E, and LpB:C-III. Compared with a reference group of healthy men (n = 103) and women (n = 106), probands with familial forms of HA had lower high-density lipoprotein cholesterol levels by selection criteria. Triglyceride levels were higher in FTgHA and FCH probands than in the reference group or FHA subjects. Despite selection of FTgHA and FCH by low-density lipoprotein (LDL) cholesterol, the latter was not significantly different between the three groups and the reference group. ApoA-I levels were decreased in FCH, FHA, and FTgHA probands, and LpA-I and LpA-I:A-II were lower in FHA and FTgHA probands. ApoB levels were significantly higher in all familial HA groups compared with the reference group, being highest in FCH individuals, but not significantly higher between FCH, FTgHA, or FHA probands. LpB:E levels were higher in the FCH and FTgHA groups than in the reference group. There were no significant differences between groups for apoE, apoC-III, and LpB:C-III. LDL particle size was smaller in all three forms of FHA, which, in combination with higher apoB levels, reflects an increased number of smaller, denser LDL particles. Affected children had, on average, higher apoB and LpB:E levels than nonaffected siblings. Our data suggest that common forms of FHA in subjects with coronary artery disease represent a spectrum of overlapping disorders characterized by an increase in apoB-containing lipoproteins, especially LpB:E particles, and smaller, denser LDL particles. When using appropriate age- and gender-adjusted cutpoints, approximately half the offspring (in young adulthood) appeared to be affected.