Apolipoprotein(a) phenotypes predict the risk for carotid atherosclerosis in patients with end-stage renal disease
F Kronenberg1, H Kathrein, P König
1Institute of Medical Biology and Human Genetics, Innsbruck, Austria.
Insights
In end-stage renal disease (ESRD) patients, the apolipoprotein(a) [apo(a)] phenotype, not just lipoprotein(a) [Lp(a)] levels, significantly predicts carotid atherosclerosis. This finding aids in assessing cardiovascular risk in dialysis patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Genetics
Background:
- Atherosclerotic complications are a leading cause of death in hemodialysis patients.
- High lipoprotein(a) [Lp(a)] plasma concentrations are an independent risk factor for atherosclerosis.
- End-stage renal disease (ESRD) patients exhibit elevated Lp(a) levels, independent of apolipoprotein(a) [apo(a)] gene size variations.
Purpose of the Study:
- To determine if Lp(a) concentrations and/or apo(a) phenotypes predict the severity of extracranial carotid artery atherosclerosis in ESRD patients.
Main Methods:
- Studied 167 ESRD patients, assessing atherosclerotic plaques in carotid arteries.
- Analyzed Lp(a) plasma concentrations and apo(a) phenotypes.
- Utilized univariate and multivariate regression analyses to identify predictors of atherosclerosis.
Main Results:
- 65% of patients had atherosclerotic plaques.
- Patients with plaques were older and had more cardiovascular history.
- Low-molecular-weight apo(a) isoforms (26.9% vs 8.5%) and higher mean Lp(a) levels (29.3 vs 19.7 mg/dL) were associated with plaques.
- Lp(a) concentration correlated with the number of affected arterial sites.
- Low-molecular-weight apo(a) phenotypes were linked to more affected arterial sites (3.62 vs 2.08).
Conclusions:
- Age and apo(a) phenotype are significant predictors of carotid atherosclerosis in ESRD patients.
- The apo(a) phenotype is a stronger predictor than Lp(a) concentration alone.
- Apo(a) phenotype can help assess general atherosclerosis risk in ESRD patients.
Abstract:
Several studies have demonstrated that atherosclerotic complications are the major cause of morbidity and mortality in hemodialysis patients. High lipoprotein(a) [Lp(a)] plasma concentrations are an independent risk factor for atherosclerosis. Patients with end-stage renal disease (ESRD) have elevated plasma concentrations of Lp(a), which are not explained by size variation at the apolipoprotein(a) [apo(a)] gene locus. The aim of our study was to investigate whether Lp(a) concentrations and/or apo(a) phenotypes are predictive of the degree of atherosclerosis in the extracranial carotid arteries in ESRD patients. Of 167 patients, 108 showed atherosclerotic plaques (65%). Univariate analysis showed that the plaque-affected group was significantly older and had a higher frequency of angina pectoris, previous myocardial infarction, or cerebrovascular accident. Furthermore, this group included significantly more patients with low-molecular-weight apo(a) isoforms (26.9% versus 8.5%, P < .005) and had significantly higher mean Lp(a) plasma concentrations (29.3 +/- 31.0 versus 19.7 +/- 25.7 mg/dL, P < .05). Lp(a) plasma concentration increased significantly with the number of affected arterial sites, from 19.7 mg/dL in patients without plaques to 40.1 mg/dL in patients with seven or eight affected sites. In patients with low-molecular-weight phenotypes, significantly more arterial sites were affected (3.62 versus 2.08, P < .001). Multivariate regression analysis showed that age, angina pectoris, and the apo(a) phenotype were the only significant predictors of the degree of atherosclerosis. We conclude that, besides age, the apo(a) phenotype is the best predictor of carotid atherosclerosis in ESRD patients and may be used for assessment of general atherosclerosis risk in this patient group.
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