By Michael Crawford, MD

Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: Hypothyroidism is common in patients undergoing percutaneous coronary interventions in a multivariate adjusted observational study was associated with worse long-term outcomes. A subgroup with repeat angiography showed that atherosclerosis progression was the likely reason.

SOURCES: Zhang M, Sara JD, Matsuzawa Y. Clinical outcomes of patients with hypothyroidism undergoing percutaneous coronary intervention. Eur Heart J 2016;37:2055-2065.

Gencer B, Rodondi N. Should we screen for hypothyroidism in patients with cardiovascular disease? Eur Heart J 2016;37:2066-2068.

Hypothyroidism is common, but missed frequently in clinical settings because the patient often is minimally symptomatic. Optimal results from percutaneous coronary interventions (PCI) involve maximizing coronary artery disease (CAD) risk factor control. Hypothyroidism can accelerate atherosclerosis and depress cardiac function, yet the relationship between hypothyroidism and the outcomes of PCI largely are unknown. Investigators from the Mayo Clinic evaluated their PCI database to determine the relationship between hypothyroidism and major adverse cardiovascular and cerebral events (MACCE) after PCI. Hypothyroidism was defined as a history of hypothyroidism or a thyroid-stimulating hormone (TSH) level > 5.0 mU/mL at the time of PCI. Those with a history of hypothyroidism were subgrouped by whether they were taking thyroid replacement and whether the therapy was adequate (TSH 0.3-5.0) or inadequate (TSH > 5.0). Also, patients were grouped according to their TSH levels euthyroid (0.3-5.0), subclinical hypothyroidism (5.0-10.0), or hypothyroidism (> 10.0). MACCE was defined as cardiac death, myocardial infarction, heart failure, repeat revascularization, or stroke.

From 1994 to 2009, more than 25,000 patients underwent PCI, and after excluding those with no follow-up angiogram, bypass surgery, a malignancy, no TSH data, or a TSH < 0.3, there were 2,430 patients left in the study, of which 686 had hypothyroidism and 1,744 were euthyroid. Median follow-up was three years. Those with hypothyroidism were older, more likely female, and had more co-morbidities such as diabetes. During the hospitalization for PCI, only heart failure was more common in those with hypothyroidism. At 10 years follow-up, after adjusting for covariates, MACCE was significantly higher in hypothyroid patients (hazard ratio [HR], 1.28; 95% confidence interval, 1.13-1.45; P = 0.0001) compared to euthyroid patients. Among the components of MACCE, only cardiac death did not reach statistical significance. Also, there was no difference in outcomes between those with subclinical hypothyroidism and hypothyroidism patients. Those who received adequate thyroid replacement therapy experienced similar outcomes to euthyroid patients, and both experienced better outcomes than those with inadequately treated or untreated hypothyroidism. A subgroup of 408 patients were randomly selected to evaluate CAD progression by subsequent angiography. Hypothyroidism exhibited a CAD higher rate of target-lesion progression (HR, 1.43, P = 0.044) and downstream progression (HR, 1.90, P = 0.006) compared to euthyroidism. The authors concluded that among patients undergoing PCI, hypothyroidism is associated with higher MACCE rates compared to euthyroid patients and that adequate thyroid replacement abrogates this risk.

COMMENTARY

As we get more subspecialized in cardiology, it is important to remember the effect of non-cardiac diseases on the progression of cardiovascular disease. This study clearly shows that post-PCI patients with overt or subclinical hypothyroidism have more MACCE and greater angiographic progression of CAD compared to euthyroid patients, even when adjusting for comorbidities such as dyslipidemia exacerbated by hypothyroidism. This suggests the absence of adequate thyroid hormones results in other deleterious effects, such as endothelial dysfunction, enhanced inflammation, and hypercoagulability, all of which have been demonstrated in experimental studies. The detection of hypothyroidism on purely clinical grounds is challenging, especially in the elderly. Thus, routine measurement of TSH in all PCI patients makes sense, and the results of this study appear to justify the small cost.

What to do with an elevated TSH is more controversial. The best approach is probably to obtain a free T4 level. If free T4 is low, then treatment with thyroid replacement seems reasonable. If the free T4 is normal, then by definition the patient has subclinical hypothyroidism (SCH). The authors found SCH in one-third of patients with elevated TSH, but they defined it solely as a TSH level between 5-10. They did not consistently measure free T4 and do not present any data on T4 levels. Other studies suggest that a TSH > 10 (and possibly TSH > 7), regardless of the free T4, should be treated. Despite the lack of a more precise definition of SCH, the patients in this study with SCH experienced better outcomes with therapy. By treating lower levels of TSH (a score between 5-7), the benefits may not counterbalance the risks of thyroid replacement such as atrial fibrillation and bone fractures, not to mention the cost and inconvenience of lifelong replacement therapy.

This study was a prospective cohort investigation, which suffers from the inability to adjust for all confounders, selection bias, and the inability to control testing and treatment. However, this is a fairly large study, with high-quality follow-up, including a subgroup with repeat angiography, and the ability to evaluate the effects of treatment. A large randomized trial of this concept has begun, but until those investigators publish the results, it is prudent to measure TSH in most PCI patients and act on the results as described above.