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Association of LDL cholesterol and inflammation with cardiovascular events and mortality in hemodialysis patients with type 2 diabetes mellitus.
Am J Kidney Dis. 2009 Nov; 54(5):902-11.AJ

Abstract

BACKGROUND

In the general population, C-reactive protein (CRP) in addition to low-density lipoprotein (LDL) cholesterol level is useful in predicting cardiovascular events. In hemodialysis patients, the additive value is unknown. The association between LDL cholesterol level and outcome previously was suggested to be inverse and confounded by inflammation.

STUDY DESIGN

Prospective cohort study.

SETTING & PARTICIPANTS

1,255 hemodialysis patients with type 2 diabetes mellitus randomly assigned to atorvastatin versus placebo in the German Diabetes Dialysis Study.

PREDICTORS

Baseline LDL cholesterol level.

OUTCOMES & MEASUREMENTS

Combined vascular end point (cardiac death, myocardial infarction, and stroke), mortality, myocardial infarction, sudden death, and stroke.

RESULTS

During 4 years, 465 combined vascular events, 612 deaths, 160 sudden deaths, 200 myocardial infarctions, and 99 strokes occurred. Median LDL cholesterol level was 123 mg/dL. LDL cholesterol level (millimoles per liter and quartiles) was not predictive of outcome. This was analyzed further in patients with and without inflammation. In patients with inflammation (CRP level > 5 mg/L), the adjusted relative risk of combined vascular events was 29% greater compared with those without inflammation and a low LDL cholesterol level (LDL cholesterol < or = 123 mg/dL). This was irrespective of whether LDL cholesterol level was low or high (hazard ratio [HR] for LDL < 123 mg/dL [HR (for LDL< or =123 mg/dL)], 1.29, with 95% confidence interval [CI], 0.98 to 1.70; HR(LDL>123 mg/dL), 1.29, with 95% CI, 0.99 to 1.69). Similar results were found for all-cause death (HR(LDL< or =123 mg/dL), 1.47 [95% CI, 1.16 to 1.86]; HR(LDL>123 mg/dL), 1.48 [95% CI, 1.16 to 1.88]), sudden death (HR(LDL< or =123 mg/dL), 1.98 [95% CI, 1.23 to 3.20]; HR(LDL>123 mg/dL), 1.66 [95% CI, 1.01 to 2.75]), and myocardial infarction (HR(LDL< or =123 mg/dL), 1.74 [95% CI, 1.14 to 2.66]; HR(LDL>123 mg/dL), 1.54 [95% CI, 0.99 to 2.38]). In patients without inflammation, the respective risks did not differ significantly between patients with varying LDL cholesterol levels. However, there was a trend toward an increased risk of myocardial infarction (HR(LDL>123 mg/dL), 1.45 [95% CI, 0.95 to 2.21]) in patients with high compared with low LDL cholesterol levels. P values for the interaction between CRP and LDL cholesterol levels were 0.9 (composite vascular end point), 0.5 (mortality), 0.9 (sudden death), 0.09 (stroke), and 0.2 (myocardial infarction).

LIMITATIONS

Selected patient cohort, post hoc analysis.

CONCLUSION

Because CRP level more than LDL cholesterol level determined outcome, the value of regular LDL cholesterol measurements in long-term hemodialysis patients with type 2 diabetes needs reassessment.

Authors+Show Affiliations

Department of Medicine I, Division of Nephrology, University of Würzburg, Germany. krane_v@medizin.uni-wuerzburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19781835

Citation

Krane, Vera, et al. "Association of LDL Cholesterol and Inflammation With Cardiovascular Events and Mortality in Hemodialysis Patients With Type 2 Diabetes Mellitus." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 54, no. 5, 2009, pp. 902-11.
Krane V, Winkler K, Drechsler C, et al. Association of LDL cholesterol and inflammation with cardiovascular events and mortality in hemodialysis patients with type 2 diabetes mellitus. Am J Kidney Dis. 2009;54(5):902-11.
Krane, V., Winkler, K., Drechsler, C., Lilienthal, J., März, W., & Wanner, C. (2009). Association of LDL cholesterol and inflammation with cardiovascular events and mortality in hemodialysis patients with type 2 diabetes mellitus. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 54(5), 902-11. https://doi.org/10.1053/j.ajkd.2009.06.029
Krane V, et al. Association of LDL Cholesterol and Inflammation With Cardiovascular Events and Mortality in Hemodialysis Patients With Type 2 Diabetes Mellitus. Am J Kidney Dis. 2009;54(5):902-11. PubMed PMID: 19781835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of LDL cholesterol and inflammation with cardiovascular events and mortality in hemodialysis patients with type 2 diabetes mellitus. AU - Krane,Vera, AU - Winkler,Karl, AU - Drechsler,Christiane, AU - Lilienthal,Jürgen, AU - März,Winfried, AU - Wanner,Christoph, AU - ,, Y1 - 2009/09/25/ PY - 2008/09/15/received PY - 2009/06/15/accepted PY - 2009/9/29/entrez PY - 2009/9/29/pubmed PY - 2009/11/17/medline SP - 902 EP - 11 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 54 IS - 5 N2 - BACKGROUND: In the general population, C-reactive protein (CRP) in addition to low-density lipoprotein (LDL) cholesterol level is useful in predicting cardiovascular events. In hemodialysis patients, the additive value is unknown. The association between LDL cholesterol level and outcome previously was suggested to be inverse and confounded by inflammation. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,255 hemodialysis patients with type 2 diabetes mellitus randomly assigned to atorvastatin versus placebo in the German Diabetes Dialysis Study. PREDICTORS: Baseline LDL cholesterol level. OUTCOMES & MEASUREMENTS: Combined vascular end point (cardiac death, myocardial infarction, and stroke), mortality, myocardial infarction, sudden death, and stroke. RESULTS: During 4 years, 465 combined vascular events, 612 deaths, 160 sudden deaths, 200 myocardial infarctions, and 99 strokes occurred. Median LDL cholesterol level was 123 mg/dL. LDL cholesterol level (millimoles per liter and quartiles) was not predictive of outcome. This was analyzed further in patients with and without inflammation. In patients with inflammation (CRP level > 5 mg/L), the adjusted relative risk of combined vascular events was 29% greater compared with those without inflammation and a low LDL cholesterol level (LDL cholesterol < or = 123 mg/dL). This was irrespective of whether LDL cholesterol level was low or high (hazard ratio [HR] for LDL < 123 mg/dL [HR (for LDL< or =123 mg/dL)], 1.29, with 95% confidence interval [CI], 0.98 to 1.70; HR(LDL>123 mg/dL), 1.29, with 95% CI, 0.99 to 1.69). Similar results were found for all-cause death (HR(LDL< or =123 mg/dL), 1.47 [95% CI, 1.16 to 1.86]; HR(LDL>123 mg/dL), 1.48 [95% CI, 1.16 to 1.88]), sudden death (HR(LDL< or =123 mg/dL), 1.98 [95% CI, 1.23 to 3.20]; HR(LDL>123 mg/dL), 1.66 [95% CI, 1.01 to 2.75]), and myocardial infarction (HR(LDL< or =123 mg/dL), 1.74 [95% CI, 1.14 to 2.66]; HR(LDL>123 mg/dL), 1.54 [95% CI, 0.99 to 2.38]). In patients without inflammation, the respective risks did not differ significantly between patients with varying LDL cholesterol levels. However, there was a trend toward an increased risk of myocardial infarction (HR(LDL>123 mg/dL), 1.45 [95% CI, 0.95 to 2.21]) in patients with high compared with low LDL cholesterol levels. P values for the interaction between CRP and LDL cholesterol levels were 0.9 (composite vascular end point), 0.5 (mortality), 0.9 (sudden death), 0.09 (stroke), and 0.2 (myocardial infarction). LIMITATIONS: Selected patient cohort, post hoc analysis. CONCLUSION: Because CRP level more than LDL cholesterol level determined outcome, the value of regular LDL cholesterol measurements in long-term hemodialysis patients with type 2 diabetes needs reassessment. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/19781835/Association_of_LDL_cholesterol_and_inflammation_with_cardiovascular_events_and_mortality_in_hemodialysis_patients_with_type_2_diabetes_mellitus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(09)00969-X DB - PRIME DP - Unbound Medicine ER -