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Inflammatory markers are independent predictors of congestive heart failure (CHF) and likely reflect the link between obesity and CHF, a new study suggests [1]. In a new analysis of the Multi-Ethnic Study of Atherosclerosis (MESA), researchers led by Dr Hossein Bahrami (Johns Hopkins, Baltimore, MD) report that serum interleukin-6 (IL-6), C-reactive protein (CRP), and albuminuria all predicted the development of CHF over four years, independent of obesity or other established risk factors.

“Our results suggest that inflammation might be involved, directly or as a marker of other underlying conditions, in the pathologic pathways that link obesity to left ventricular [LV] dysfunction and ultimately CHF,” Bahrami et al write.

The study appears in the May 6, 2008 issue of the Journal of the American College of Cardiology.

Authors of the study calculated the hazard ratios (HRs) linking baseline metabolic syndrome, inflammatory markers, insulin resistance, and albuminuria with incidence CHF in the MESA population, after taking into account standard risk factors, interim myocardial infarction (MI), and left ventricular structure and function. MESA enrolled 6814 participants from multiple ethnic backgrounds; median follow-up for the current analysis was four years.

Baharmi and colleagues report that 79 patients developed CHF during follow-up: while obesity was significantly associated with subsequent CHF, the association lost statistical significance after inflammatory markers were included in the model. Obese patients, however were found to have much higher levels of interleukin 6, CRP, and fibrinogen.

According to Baharmi, the findings suggest a mechanistic link between obesity, inflammation, and CHF.

“The implication may be that greater control of obesity may reduce the risk of heart failure and down the road, maybe targeting inflammatory markers may reduce the risk of heart failure related to obesity,” he told heartwire.

Inflammation may also help explain the link between the metabolic syndrome and CHF risk: inflammation is a known characteristic of the metabolic syndrome, and metabolic syndrome is associated with a higher risk of developing CHF, the authors note.

The National Heart, Lung, and Blood Institute supported this study.

Source

1. Bahrami H, Bluemke DA, Kronmal R, et al. Novel metabolic risk factors for incident heart failure and their relationship with obesity. The Multi-Ethnic Study of Atherosclerosis Study. J Am Coll Cardiol. 2008;51:1775-1783.

Clinical Context

The prevalence of CHF continues to rise in the United States, in part because of an increasing prevalence of obesity and metabolic syndrome and its factors. Other risk factors for CHF include male sex, age, LV hypertrophy, hypertension (HTN), MI, diabetes, and valvular heart disease. Inflammatory markers such as IL-6 and CRP may be markers predictive for CHF and may be intermediaries for the risk factors for obesity and metabolic syndrome.

This is a longitudinal multicenter cohort study of a multiethnic group of US participants from 6 communities to examine the effect of different risk factors for CHF and the contribution of inflammatory markers as predictors of CHF in healthy individuals.
Study Highlights

* Included were 6814 men and women aged 45 to 84 years at baseline (3601 women), of whom 38% were Caucasian, 28% African American, 22% Hispanic, and 12% Chinese American.
* Excluded were those with cardiovascular disease at baseline.
* At baseline, standardized questionnaires were administered, and body mass index, blood pressure and glucose, insulin, lipids and other laboratory values were determined.
* Body mass index was classified as obesity (> 30 kg/m2), overweight (25 - 29.9 kg/m2), and normal, HTN as blood pressure of more than 140/90 mm Hg or use of antihypertensives medications, and diabetes as fasting blood glucose levels of more than 126 mg/dL or use of hypoglycemic agents.
* The metabolic syndrome was defined by the Adult Treatment Panel III criteria with at least 3 of the following met: abdominal obesity (waist circumference > 102 cm in men and 88 cm in women), serum triglyceride levels of 150 mg/dL or more, high-density lipoprotein (HDL) cholesterol levels less than 40 mg/dL in men and 50 mg/dL in women, blood pressure 130/85 mm Hg or higher or use of antihypertensive medications, and fasting blood glucose levels of 110 mg/dL or higher or use of hypoglycemic agents.
* Serum levels of IL-6, CRP, and fibrinogen were measured as markers of systemic inflammation.
* LV function and structure were determined by magnetic resonance imaging in 73.4% of participants, and echocardiography was performed in all participants.
* Median follow-up was 4 years for 25,107 person-years of observation.
* Primary endpoint was symptomatic CHF diagnosed by a clinician.
* Other outcome was MI defined by biomarkers, electrocardiogram, and symptoms.
* CHF developed in 79 participants for an incidence rate of 3.1 per 1000.
* Those in whom CHF developed were more likely to be older, men, obese, current smokers, and have HTN and diabetes.
* Obese participants had an absolute risk for CHF of 16 vs 10 per 1000 for CHF with an attributable risk for 6 per 1000.
* The attributable risk for HTN and diabetes were 11 and 19 per 1000, respectively.
* Of the 79 with CHF, 32.9% had an interim MI before CHF and 3.8% had a clinical MI after a diagnosis of CHF.
* The metabolic syndrome was present in 34.7% at baseline and the HR for CHF was 2.04, with an attributable risk for 8 per 1000.
* Among the metabolic syndrome criteria, triglyceride and HDL cholesterol levels were not significant predictors of CHF.
* Plasma glucose levels and abdominal obesity were the strongest predictors of CHF among the metabolic syndrome criteria.
* Among the inflammatory markers, IL-6 was the strongest predictor for CHF (HR, 1.84 for each SD increase in log serum IL-6) with an attributable risk for 13 per 1000 for the top vs the lowest 3 quartiles.
* A CRP level of 5 mg/dL or more was associated with an 87% increased risk for CHF (HR, 1.87), with an attributable risk for 8 per 1000.
* Higher fasting glucose levels at baseline and macroalbuminuria and microalbuminuria (HR, 9.47 and 4.40, respectively) were significant predictors for CHF.
* The predictive value of serum IL-6, CRP, and fibrinogen as well as macroalbuminuria and microalbuminuria were independent of established CHF risk factors.
* LV hypertrophy, LV ejection fraction, LV end-diastolic volume, and LV mass to end-diastolic volume at baseline were predictors for CHF with LV ejection fraction as the strongest predictor.
* The occurrence of MI during interim follow-up was a strong predictor for CHF (HR, 112.24).
* The authors concluded that inflammatory markers and albuminuria were independent predictors of CHF beyond traditional risk factors and the development of interim MI.

Pearls for Practice

* Among traditional risk factors for CHF, abdominal obesity and plasma glucose levels for the metabolic syndrome and interim MI are strong predictors.
* Inflammatory markers and macroalbuminuria and microalbuminuria are strong independent predictors for CHF.

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