Impact of Subclinical Hypothyroidism on Cardiometabolic Biomarkers in Women
Paulo H N Harada1,2,3, Julie E Buring2,4, Nancy R Cook2,4
1Center for Lipid Metabolomics, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Insights
Subclinical hypothyroidism (SCH) and overt hypothyroidism (HT) are linked to worsening insulin resistance and increased cardiovascular disease risk markers in women. These risks appear early, even with normal cholesterol levels.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Metabolic Health
Background:
- The association between subclinical hypothyroidism (SCH) and cardiometabolic abnormalities remains unclear.
- Understanding these links is crucial for early cardiovascular disease (CVD) risk assessment.
Purpose of the Study:
- To investigate cardiometabolic biomarkers in women with euthyroid, SCH, and overt hypothyroidism (HT).
- To assess CVD risk markers across different thyroid function statuses in women without pre-existing CVD.
Main Methods:
- A cross-sectional study analyzed associations between thyroid status (euthyroid, SCH, HT) and various cardiometabolic biomarkers.
- Data included lipids, lipoprotein subclasses, insulin resistance scores, inflammatory markers, coagulation factors, and glycemic biomarkers.
- Analyses were adjusted for confounders in a subcohort of the Women's Health Study (n=3,321).
Main Results:
- Progression from euthyroid to overt hypothyroidism showed unfavorable lipoprotein subclass profiles, indicating insulin resistance.
- Subclinical hypothyroidism and overt hypothyroidism were associated with higher high-sensitivity C-reactive protein (hs-CRP) and HbA1c levels.
- Increasing thyroid-stimulating hormone (TSH) levels correlated with these adverse cardiometabolic changes.
Conclusions:
- Subclinical hypothyroidism is associated with poorer cardiometabolic profiles, including worsening insulin resistance and elevated CVD risk markers, compared to euthyroid states.
- Cardiometabolic risk may escalate early in the progression from euthyroid to subclinical and overt hypothyroidism.
- These findings highlight the importance of monitoring cardiometabolic health in individuals with even mild thyroid dysfunction.
Context:
Whether subclinical hypothyroidism (SCH) is associated with cardiometabolic abnormalities is uncertain.
Objective:
To examine diverse cardiometabolic biomarkers across euthyroid, SCH, and overt hypothyroidism (HT) in women free of cardiovascular disease (CVD).
Design:
Cross-sectional adjusted associations for lipids, lipoprotein subclasses, lipoprotein insulin resistance score, inflammatory, coagulation, and glycemic biomarkers by ANCOVA for thyroid categories or TSH quintiles on a Women's Health Study subcohort.
Setting:
Outpatient.
Patients Or Other Participants:
Randomly sampled 3,914 middle-aged and older women for thyroid function analysis (thyroid-stimulating hormone [TSH], free T4), of whom 3,321 were not on lipid lowering therapy.
Intervention:
None.
Main Outcome Measure:
Associations of SCH and HT with cardiometabolic markers.
Results:
Going from euthyroid to HT, the lipoprotein subclasse profiles were indicative of insulin resistance [respective values and p for trend]: larger VLDL size (nm)[51.5 (95%CI51.2, 51.8) to 52.9 (51.8, 54.1) p=0.001]; higher LDL particles concentration (nmol/L)[1283 (95%CI1267, 1299) to 1358 (1298, 1418) p=0.004] and smaller LDL size. There was worsening lipoprotein insulin resistance score from euthyroid 49.2 (95%CI 48.3, 50.2) to SCH 52.1 (95%CI 50.1, 54.0), and HT 52.1 (95%CI 48.6, 55.6), p for trend 0.008. Of the other biomarkers, SCH and HT were associated with higher hs-CRP and HbA1c. For increasing TSH quintiles results were overall similar.
Conclusions:
In apparently healthy women, SCH cardiometabolic profiles indicated worsening insulin resistance and higher CVD risk markers compared with euthyroid individuals, despite similar LDL and total cholesterol. These findings suggest that cardiometabolic risk may increase early in the progression towards SCH and OH.
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