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Hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) excess in maintenance dialysis patients: a matched
A G Bostom1, D Shemin, K L Lapane
1Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts New England Medical Center, Boston, MA 02111, USA.
Insights
Dialysis patients have higher levels of non-traditional cardiovascular disease (CVD) risk factors like hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) excess. These factors, especially when combined, significantly increase CVD risk in dialysis patients beyond traditional markers.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biochemistry
Background:
- Maintenance dialysis patients exhibit a high incidence of arteriosclerotic cardiovascular disease (CVD) events.
- Traditional CVD risk factor indices inadequately predict CVD events in this population.
Purpose of the Study:
- To evaluate the prevalence of three non-traditional CVD risk factors: hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) [Lp(a)] excess.
- To assess the combined effect of these non-traditional risk factors in maintenance dialysis patients.
Main Methods:
- Assessed plasma levels of homocysteine (Hcy), fibrinogen, Lp(a), glucose, and cholesterol in 71 dialysis patients and 71 controls.
- Evaluated traditional CVD risk factors (glucose tolerance, smoking, hypertension, dyslipidemia) in both groups.
Main Results:
- Dialysis patients showed significantly higher mean plasma levels of Hcy, fibrinogen, and Lp(a) compared to controls.
- Odds ratios for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, individually and combined, were markedly greater in dialysis patients.
- The increased risk associated with these factors was not confounded by traditional CVD risk factors.
Conclusions:
- Combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may significantly contribute to the high incidence of vascular disease in dialysis patients.
- These non-traditional risk factors inadequately explained by traditional CVD risk factors.
- Prospective studies are needed to confirm this hypothesis and guide interventions.
Abstract:
Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poorly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) Lp(a)) excess, and combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, in maintenance dialysis patients. Fasting total plasma homocysteine (Hcy), fibrinogen, Lp(a), glucose, and total and HDL cholesterol levels, and traditional CVD risk factor (i.e. glucose tolerance, smoking, hypertension, dyslipidemia) prevalences were assessed in 71 dialysis patients and 71 age, sex, and race matched Framingham Study controls free of clinical renal disease, with normal serum creatinine (< or = 1.5 mg/dl). Mean plasma Hcy 23.7 vs. 9.9 microM, P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/dl, P = 0.0070) levels were substantially increased in the dialysis patients. Matched odds ratios (with 95% confidence intervals), dialysis patients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia, 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35.0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incidence of vascular disease sequelae experienced by dialysis patients, which is inadequately explained by traditional CVD risk factors. Controlled, prospective studies of well-characterized maintenance dialysis cohorts are urgently required to substantiate this hypothesis.