This study suggested that hypothyroidism is independently associated with higher rate of perfusion abnormality on SPECT MPI, regardless of presence of other known CAD risk factors.
Previous studies have shown that the cardiovascular complications of hypothyroidism, such as heart failure and CAD, is relatively common and impaired thyroid function can cause significant changes in hemodynamics of the heart, including endothelial cell dysfunction, increased risk of atherosclerosis, and increased prevalence and severity of CAD[18]. Although these changes can be partly associated with abnormal lipid metabolism in hypothyroid patients, the presence of a real cause and effect relationship between hypothyroid state and CAD is still controversial[19, 20].
Different studies have shown a relationship between clinical and subclinical hypothyroidism and increased risk of atherosclerosis and CAD, diagnosed by various imaging modalities [12, 21, 22]. Sara et al. conducted a study on patients who had non-obstructive CAD on coronary angiography, and assessed coronary artery endothelial-dependent microvascular and epicardial function by evaluating changes in coronary blood flow and diameter, in response to intracoronary infusions of acetylcholine. They found that hypothyroid female patients presented significantly lower change in coronary blood flow after acethylecholine infusion, suggestive of microvascular endothelial dysfunction. Also, Sara et al. who studied the relationship between hypothyroidism and endothelial dysfunction of coronary arteries using angiography, found that women with hypothyroidism had a significantly lower percentage of coronary blood flow change, indicating a strong relationship between hypothyroidism in women and endothelial microvascular dysfunction of the coronary arteries with increased risk of cardiovascular disease in these patients[9]. In a larger study by Bai et al., 605 patients suspected of CAD who underwent coronary angiography were evaluated with thyroid function test before angiography and were categorized to euthyroidism, low T3 syndrome (decreased fT3 level with normal TSH and fT4 levels) and hypothyroidism (increased TSH level in association with reduced fT3 or fT4 levels) groups. The prevalence of CAD and its severity in all three subgroups were then assessed based on invasive coronary angiography [8]. In this study, 83.3% of patients with low T3 syndrome and 81.5% of hypothyroid patients had angiographic evidence in favor of CAD, which was significantly higher than that of euthyroid individuals[8]. However, when quantitatively assessed CAD by SYNTAX score on angiography, no significant correlation was detected between severity of CAD and subclinical hypothyroidism[23, 24]. Nonetheless, high TSH level was associated with greater MACE event in patients with CAD on angiography[23]. In a cohort of 1047 patients, referred for angiography, a significant association was found between FT3 levels and severity of CAD in coronary angiography. Patients with lower T3 levels had worse prognosis and higher mortality, as well[10]. Since the most patients who are candidate for coronary angiography are at a higher risk for CAD, the prevalence of CAD is higher in the both the total study population and hypothyroid groups of these mentioned studies as compared to our study. Despite that in the current study patients with lower CAD risk who were candidate for noninvasive MPI SPECT were selected the correlation of hypothyroidism with evidence of abnormal perfusion on MPI scan was still significant, indicating the importance of the link between hypothroidism and CAD even in patients with lower CAD risk.
Other noninvasive imaging method also revealed the correlation of hypothyroidism and evidence of CAD. In a large study by Park et al., 2404 intermediate to high risk patients who underwent cardiac CT were evaluated with 49 patients found to have subclinical hypothyroidism. CAD (defined as stenosis > 50%) and calcium score > 100 were more prevalent in patients with subclinical hypothyroidism (63.3% vs 40.6%)[12]. Bernstein et al., conducted a study for detection of silent myocardial ischemia in patients with chronic and severe hypothyroidism using Tl201-SEPCT MPI[14]. In this study, exercise Tl201- MPI SPECT, ECG and echocardiography were performed for 6 patients with acute severe hypothyroidism, being scheduled for radioactive iodine therapy. Four of these patients revealed substantial reversible perfusion defect in SPECT MPI that reverted to normal pattern after 2 months of thyroid hormone replacement therapy[14]. Aydin et al., designed a study for evaluating left ventricular (LV) function by gated SPECT in acute hypothyroidism [15]. The major findings of their study were reduction in peak filling rate (PFR) and prolongation in time to peak filling (TTPF) demonstrated by gated SPECT in patients with acute hypothyroidism compared to control group, suggesting LV diastolic dysfunction. During thyroxine therapy, PFR improved, but TTPF did not change significantly [15]. These studies in addition to our results further indicated the correlation of CAD with subclinical and clinical hypothyroidism in lower risk patients and emphasized on the role of thyroid function as an independent factor for development of CAD.