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CLINICAL RESEARCH: HEART FAILURE

Subclinical Thyroid Dysfunction, Cardiac Function, and the Risk of Heart Failure

The Cardiovascular Health Study

Nicolas Rodondi, MD, MAS^_*,_*, Douglas C. Bauer, MD^,, Anne R. Cappola, MD, ScM, Jacques Cornuz, MD, MPH^_*, John Robbins, MD, MHS^||, Linda P. Fried, MD, MPH^¶, Paul W. Ladenson, MD^#, Eric Vittinghoff, PhD, John S. Gottdiener, MD, FACC^_** and Anne B. Newman, MD, MPH

^_* Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland
Department of Epidemiology and Biostatistics, University of California, San Francisco, California
Division of General Internal Medicine, University of California, Department of Medicine, San Francisco, California
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
^|| University of California, Davis, Sacramento, California
^¶ Division of Geriatric Medicine and Gerontology and Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, Maryland
^# Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins, University School of Medicine, Baltimore, Maryland
^_** Echocardiography Laboratory, Division of Cardiology, University of Maryland Hospital, Baltimore, Maryland
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Manuscript received January 23, 2008; revised manuscript received May 27, 2008, accepted July 10, 2008.

^_* Reprint requests and correspondence: Dr. Nicolas Rodondi, Department of Ambulatory Care and Community Medicine, University of Lausanne, Bugnon 44, 1011 Lausanne, Switzerland (Email: Nicolas.Rodondi{at}hospvd.ch).

Objectives: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities.

Background: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited.

Methods: We studied 3,044 adults 65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, 10.0 mU/l), and those with subclinical hyperthyroidism.

Results: Over the course of 12 years, 736 participants developed HF events. Participants with TSH 10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p = 0.01; adjusted hazard ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH 10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p = 0.002). Over the course of 5 years, left ventricular mass increased among those with TSH 10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF.

Conclusions: Compared with euthyroid older adults, those adults with TSH 10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH <10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH 10.0 mU/l.

Key Words: subclinical thyroid dysfunction • heart failure • echocardiography • cohort study

Abbreviations and Acronyms   CHS = Cardiovascular Health Study   CI = confidence interval   CVD = cardiovascular disease   FT4 = free thyroxine   HF = heart failure   HR = hazard ratio   LV = left ventricular   RCT = randomized controlled trial   TSH = thyroid-stimulating hormone

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