The Association Between Subclinical Hypothyroidism and Cardiovascular Disease Risk: A Review of Epidemiological Evidence

Abstract

Introduction: Subclinical hypothyroidism (SCH), a condition defined by an elevated serum thyroid-stimulating hormone (TSH) level with normal free thyroxine concentrations, is a common biochemical finding. Its clinical importance, particularly its role as a potential risk factor for atherosclerotic cardiovascular disease (CVD), has been the subject of considerable investigation and debate.

Literature Review: A review of the pivotal literature reveals a consistent association between SCH and an adverse cardiovascular risk profile. Multiple cross-sectional studies and meta-analyses established a clear link between SCH and higher levels of total and LDL cholesterol. Research also suggested associations with other non-lipid risk factors, such as endothelial dysfunction and markers of subclinical atherosclerosis. Large-scale prospective cohort studies and meta-analyses provided evidence that SCH is associated with an increased risk of developing coronary heart disease events and cardiovascular mortality. This risk appeared to be most pronounced in younger individuals and those with higher TSH levels, particularly concentrations above 10 mIU/L. Despite this evidence of association, the question of whether treating SCH with levothyroxine reduces these clinical cardiovascular endpoints remained largely unanswered by randomized trials during this period.

Conclusion: The body of evidence successfully characterized subclinical hypothyroidism not as a benign laboratory finding but as a genuine risk factor for cardiovascular disease. This research established a strong rationale for viewing SCH through a lens of cardiovascular risk, although it left the debate over broad-based treatment to prevent clinical events unresolved.