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Subclinical hypothyroidism and coronary heart disease: A case for early detection and treatment

Subclinical hypothyroidism and coronary heart disease: A case for early detection and treatment

Even mild cases of thyroid disease are linked to coronary heart disease, lipid abnormalities and left ventricular dysfunction. Replacement therapy in younger patients can reduce the risk of coronary heart disease and its complications

Introduction

Presentation of patients with thyroid disorders can range from those with overt illness at both ends of the spectrum to those with milder abnormalities somewhere around the middle. In epidemiological studies, those with subclinical forms outnumber those with overt disease. Individuals with milder forms of thyroid disorder need to be identified as there are important consequences associated with even the milder forms of the disorder.

Subclinical hypothyroidism and coronary heart disease

For at least 10 years it has been recognized that subclinical hypothyroidism (SCH) is associated with an increased risk of coronary heart disease (CHD). Experts in 2006 initiated clinical trials that would show whether thyroid hormone replacement therapy could reduce the risk of CHD in patients with SCH.1

Results of a meta-analysis by the Thyroid Studies Collaboration in 2014 have shown that compared with euthyroid individuals, people with SCH have a 200 times higher risk of CHD events (HR: 2.6 [95% CI, 1.43 to 4.74]), despite being thyroid peroxidase antibody (TPO) negative. Those with SCH and positive anti-TPO antibody had an even higher risk of CHD mortality (HR: 1.8 [95% CI, 1.07 to 3.01]).2

The lipid link

The effect of SCH on the lipid profile of these patients may be a probable explanation for the increase in CHD risk. Overt hypothyroidism is associated with lipid abnormalities due to the reduced activity of lipoprotein lipase and hepatic lipase resulting in hypercholesterolaemia with increased low density lipoprotein cholesterol.3 Mild thyroid failure, such as SCH, is also significantly associated with elevated total cholesterol, low density lipoprotein and triglycerides,4 which contribute to atheroma, plaque formation and subsequent coronary atherothrombotic events.

Left ventricular function

Clinical studies have investigated why SCH leads to an increased risk of CHD. Several studies have linked the detrimental effects of SCH to left ventricular (LV) function, including a meta-analysis using tissue Doppler echocardiography in patients less than 60 years. This study found patients with SCH had significantly worse LV diastolic function compared with euthyroid patients.5

Benefits of replacement therapy

A more important question is the benefit of treatment to the systolic and diastolic function of patients with SCH. A randomized, double-blind, placebo-controlled trial of middle-aged women with SCH compared levothyroxine replacement with placebo over the course of one year. Echocardiographic evaluation revealed that those who did not receive levothyroxine had significant deterioration in their LV function, cardiac output and cardiac index.6

With this body of evidence, there is a strong case for detecting mild thyroid failure (SCH) early and instituting replacement therapy in appropriate patients (younger patients) in order to reduce the risk of CHD and its sequelae.


References

  1. Rodondi N, et al. Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Am J Med 2006;119:541–51.
  2. Collet TH, et al. for the Thyroid Studies Collaboration. Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis. J Clin Endocrinol Metab 2014;99:3353–62.
  3. O’Brien T, et al. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc 1993;68:860–6.
  4. Liu X-L, et al. Alteration of lipid profile in subclinical hypothyroidism: A meta-analysis. Med Sci Monit 2014;20:1432–41.
  5. Chen X, et al. Evaluation of left ventricular diastolic function using tissue Doppler echocardiography in patients with subclinical hypothyroidism aged <60 years: A meta-analysis. J Cardiol 2013;61:8–15.
  6. Martins RM, et al. Impact of subclinical hypothyroidism treatment in systolic and diastolic cardiac function. Arq Bras Endocrinol Metab 2011;55:460–7.

 

Nemencio Nicodemus Jr.

Professor
Department of Biochemistry & Molecular Biology
College of Medicine
University of the Philippines
Manila, Philippines
Clinical Associate Professor
Department of Medicine
Philippine General Hospital
Manila, Philippines
subclinical hypothyroidism
coronary heart disease
replacement therapy