Both Hyper- and Hypothyroidism Linked to CV Events

April 26, 2012

April 25, 2012 (Bern, Switzerland and Gateshead, United Kingdom) — Mild degrees of hyperthyroidism or hypothyroidism both appear to be associated with an increased risk of cardiovascular events [1,2]. And treatment of hypothyroidism with levothyroxine may reduce this risk, at least in younger patients.

These are the conclusions of two new studies published online April 23, 2012 in the Archives of Internal Medicine.

Correcting Hypothyroidism Reduces CV Risk?

Lead author of the hypothyroidism study, Dr Salman Razvi (Gateshead Health, UK), explained to heartwire : "A number of studies have previously shown that subclinical hypothyroidism may be associated with ischemic heart disease, particularly in younger patients, but there has not yet been a study showing that cardiovascular events are reduced by correcting the condition."

Razvi and colleagues used data from the UK GP database to identify 4735 patients diagnosed with subclinical hypothyroidism in 2001 and followed them until 2009. Around half the patients were treated with levothyroxine, and the other half received no treatment. Results were analyzed with respect to age.

Results showed that treatment with levothyroxine was associated with a reduced risk of cardiovascular events in younger patients, but not in older patients.

Cardiovascular Events in Patients With Subclinical Hypothyroidism

Age Levothyroxine


No treatment (%) Adjusted HR (95% CI)
40–70 (n=3093) 4.2 6.6 0.61 (0.39–0.95)
>70 (n=1642) 12.7 10.7 0.99 (0.59–1.33)

Razvi noted that subclinical hypothyroidism is very common, occurring in about 5% of the population. Thyroid-function tests are one of the most frequently conducted tests by GPs, often being requested when patients complain of tiredness or weight gain. Subclinical hypothyroidism is defined as elevation of thyroid-stimulating hormone (TSH) with normal thyroid hormone levels, and there is controversy about whether or not this mild form of the disease requires treatment.

Razvi said his results were not definitive, as this was just an observational study, and that a randomized trial is needed to confirm the findings. Speculating on the difference between the younger and older groups, Razvi said it is believed that older people may have naturally higher TSH levels than younger individuals and may need lower levels of thyroxine, and the association between mild hypothyroidism and cardiovascular events is not as strong in older patients. "Although we say these older patients have subclinical hypothyroidism because they have elevated TSH levels, this in fact may be normal for that age."

Hyperthyroidism Increases CV Risk Too

In the second study, a team led by Dr Nicolas Rodondi (University of Bern, Switzerland) pooled individual patient data from 10 cohort studies to investigate the association between subclinical hyperthyroidism and cardiovascular events.

Rodondi commented to heartwire : "The risk associated with subclinical hyperthyroidism was unclear until this study. There have been conflicting data from many studies. We have put all the data together in an individual patient meta-analysis, and we showed a clear increase in risk of atrial fibrillation and coronary heart disease mortality. We also found the level of TSH correlated with cardiovascular risk."

The researchers pooled individual data from cohort studies including 52 674 participants. Of these, 2188 patients had subclinical hyperthyroidism. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality, CHD mortality, CHD events, and AF.

Hazard Ratios for CV Events in Patients With Subclinical Hyperthyroidism vs Those Without The Condition

Event Adjusted HR (95% CI)
Total mortality 1.24 (1.06–1.46)
CHD mortality 1.29 (1.02–1.62)
CHD events 1.21 (0.99–1.46)
AF 1.68 (1.16–2.43)

Rodondi said: "Our results are consistent with most guidelines, which recommend that persistent subclinical hyperthyroidism be treated among the elderly and those with heart disease. The next question is whether we should screen everyone for hypo- or hyperthyroidism. The current data probably aren't enough to make recommendations on this. We need randomized controlled trials such as the ongoing TRUST study."

On the mechanisms involved in the link between thyroid disease and heart disease, Rodondi said these were clearer for hypothyroidism, which is associated with traditional cardiovascular risk factors such as increases in weight, cholesterol, and blood pressure. "The mechanisms connecting hyperthyroidism to heart disease are more complex. It could be related to a faster heart rate, as hyperthyroidism does seem to be associated with arrhythmias."

In an accompanying editorial [3], Dr Kenneth Burman (Washington Hospital Center, DC) says: "Until further data are available, the relationship between subclinical hyperthyroidism and increased mortality, CHD mortality, and atrial fibrillation [currently] provides sufficient evidence to consider treatment of subclinical hyperthyroidism, especially in elderly patients with cardiac risks, hyperthyroid symptoms, or osteoporosis."