Subclinical hypothyroidism is significantly associated with lower serum levels of small high-density lipoprotein (HDL) cholesterol particle (HDL-P) subfractions, while subclinical hyperthyroidism is associated with lower levels of large HDL-P subfractions. This is according to findings published in Atherosclerosis.

Investigators conducted a longitudinal, prospective cohort study, recruiting civil servants (N=3304) from 6 cities across Brazil to participate in this study. Participants were assessed by an immunoenzymatic assay for hormone levels and by spectroscopy for lipoprotein levels. Particles were defined by size as small HDL-P (7.4 nm-7.8 nm), intermediate HDL-P (8.7 nm-9.5 nm), and large HDL-P (10.3 nm-12 nm).

Participants were mostly women (54.1%) aged mean 50.6 (±8.7) years, and 51.2% were White. Participants were stratified into euthyroidism (n=3039), subclinical hypothyroidism (n=226), and subclinical hyperthyroidism (n=39) groups.

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Participant groups were well-balanced for rate of diabetes, alcohol consumption, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol levels; however, smoking (P <.001), body mass index (P =.003), waist circumference (P =.040), systolic blood pressure (P =.009), and triglyceride levels (P <.001) differed significantly between euthyroid and hypothyroid groups.

Compared with the euthyroid group, those with hypothyroidism had significantly lower levels of small HDL-P (b, -0.48; 95% CI, -0.90 to -0.06; P =.026), and those with hyperthyroidism had higher levels of intermediate HDL-P (b, 0.68; 95% CI, 0.002-1.35; P =.049).

After correcting for demographic information, hypothyroidism remained statistically correlated with small HDL-P (b, -0.46; 95% CI, -0.87 to -0.05; P =.026), but hyperthyroidism was not associated with intermediate HDL-P (b, 0.65; 95% CI, -0.01 to 1.32; P =.055) or large HDL-P (b, -0.36; 95% CI, -0.79 to 0.06; P =.092).

The association between hypothyroidism and fewer small HDL-Ps remained robust after correcting for comorbidities (b, -0.50; 95% CI, -0.90 to -0.10; P =.014), lifestyle factors (b, -0.47; 95% CI, -0.88 to -0.06; P =.024), and cholesterol (b, -0.60; 95% CI, -0.99 to -0.21; P =.003).

Hyperthyroidism became more closely associated with fewer large HDL-Ps in models that corrected for comorbidities (intermediate: b, 0.65; 95% CI, -0.02 to 1.31; P =.057 vs large: b, -0.41; 95% CI, -0.82 to -0.01; P =.044), lifestyle factors (intermediate: b, 0.64; 95% CI, -0.04 to 1.32; P =.065 vs large: b, -0.39; 95% CI, -0.80 to 0.20; P =.063), and cholesterol (intermediate: b,0.72; 95% CI, 0.11-1.32; P =.021 vs large: b, -0.38; 95% CI, -0.65 to -0.12; P =.004).

The major limitation of this study was the cross-sectional design, which impeded the investigators from making causal relationships between cholesterol particles and disease status.

The study authors concluded that HDL particle size was associated with hypothyroidism and hyperthyroidism. These data indicated that individuals with subclinical hypothyroidism may be at an increased risk for cardiovascular complications.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Janovsky CCPS, Generoso G, Goulart AC, et al. Differences in HDL particle size in the presence of subclinical thyroid dysfunctions: the ELSA-Brasil study. Published online September 11, 2020. Atherosclerosis. doi: 10.1016/j.atherosclerosis.2020.08.021