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Inflammation enhances cardiovascular risk and mortality in hemodialysis patients
J Zimmermann1, S Herrlinger, A Pruy
1Department of Medicine, University Clinic Würzburg, Germany. j.zimmermann@medizin.uni-wuerzburg.de
Insights
In hemodialysis patients, an activated acute phase response, indicated by elevated C-reactive protein (CRP), is linked to increased cardiovascular risk factors and mortality. Addressing inflammation may improve survival in these patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Inflammation Biology
Background:
- Atherosclerosis is a significant inflammatory complication in chronic hemodialysis patients.
- C-reactive protein (CRP) is a key marker of acute phase reactions and a predictor of cardiovascular mortality.
- The study investigates the link between acute phase response markers and cardiovascular risk factors in hemodialysis patients.
Purpose of the Study:
- To determine if acute phase reactions influence cardiovascular risk factors and mortality in hemodialysis patients.
- To assess the relationship between C-reactive protein (CRP) and serum amyloid A (SAA) with various cardiovascular risk markers.
- To evaluate the predictive value of acute phase response markers for mortality in this population.
Main Methods:
- Serum lipids, apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)], fibrinogen, and serum albumin (Salb) were measured in 280 hemodialysis patients.
- Levels of CRP and SAA were assessed as markers of acute phase response.
- Patient mortality was prospectively monitored over a two-year period.
Main Results:
- Elevated CRP or SAA (in 46-47% of patients) correlated with higher Lp(a), fibrinogen, and lower high-density lipoprotein cholesterol, apo A-I, and Salb.
- Patients with elevated CRP or SAA showed significantly higher overall and cardiovascular mortality rates (31% vs. 16% and 29% vs. 19%, respectively).
- Multivariate analysis identified age and CRP as independent predictors of mortality, while SAA, fibrinogen, apo A-I, and Lp(a) lost predictive value.
Conclusions:
- A significant proportion of hemodialysis patients exhibit an activated acute phase response.
- This inflammatory state is associated with atherogenic vascular risk factors and increased cardiovascular death.
- Targeting the inflammatory condition could potentially enhance long-term survival in hemodialysis patients.
Background:
Atherosclerosis, a major problem in patients on chronic hemodialysis, has been characterized as an inflammatory disease. C-reactive protein (CRP), the prototypical acute phase protein in humans, is a predictor of cardiovascular mortality in the general population. We hypothesize that several of the classic, as well as nontraditional, cardiovascular risk factors may respond to acute phase reactions. An activated acute phase response may influence or predict cardiovascular risk.
Methods:
In 280 stable hemodialysis patients, serum lipids, apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)], fibrinogen, and serum albumin (Salb) were determined in relation to CRP and serum amyloid A (SAA), two sensitive markers of an acute phase response. Mortality was monitored prospectively over a two year period.
Results:
Serum CRP and SAA were found to be elevated (more than 8 and more than 10 mg/liter, respectively) in 46% and 47% of the patients in the absence of clinically apparent infection. Patients with elevated CRP or SAA had significantly higher serum levels of Lp(a), higher plasma fibrinogen, and lower serum levels of high-density lipoprotein cholesterol, apo A-I, and Salb than patients with normal CRP or SAA. The rise in Lp(a) concentration was restricted to patients exhibiting high molecular weight apo(a) isoforms. During follow-up, 72 patients (25.7%) had died, mostly due to cardiovascular events (58%). Overall mortality and cardiovascular mortality were significantly higher in patients with elevated CRP (31% vs. 16%, P < 0.0001, and 23% vs. 5%, P < 0.0001, respectively) or SAA (29% vs. 19%, P = 0.004, and 20 vs. 10%, P = 0.008, respectively) and were also higher in patients with Salb of lower than 40 g/liter (44% vs. 14%, P < 0.0001, and 34% vs. 6%, P < 0.0001, respectively). Univariate Cox regression analysis demonstrated that age, diabetes, pre-existing cardiovascular disease, body mass index, CRP, SAA, Salb, fibrinogen, apo A-I, and Lp(a) were significantly associated with the risk of all-cause and cardiovascular mortality. During multivariate regression analysis, SAA, fibrinogen, apo A-I, and Lp(a) lost their predictive values, but age and CRP remained powerful independent predictors of both overall death and cardiovascular death.
Conclusion:
These results suggest that a considerable number of hemodialysis patients exhibit an activated acute phase response, which is closely related to high levels of atherogenic vascular risk factors and cardiovascular death. The mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. A successful treatment of the inflammatory condition may improve long-term survival in these patients.