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From Hypothyroidism to Coronary Heart Disease: Unraveling the Lipid Profile Link: A Mendelian Randomization Study
Jinjian Li1, Siyu Long1, Boyuan Liu1
1Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510080, China.
Insights
Hypothyroidism causally increases coronary heart disease (CHD) risk, mediated by altered high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels. Monitoring lipids in hypothyroid patients is crucial for CHD prevention.
Area of Science:
- Endocrinology and Cardiology
- Genetic Epidemiology
- Metabolic Disorders
Background:
- The relationship between hypothyroidism and coronary heart disease (CHD) remains debated, particularly concerning its impact on lipid metabolism.
- Understanding the causal pathways is essential for effective prevention and treatment strategies for cardiovascular disease in hypothyroid individuals.
Purpose of the Study:
- To investigate the causal effect of hypothyroidism on the development of CHD.
- To examine the potential mediating role of lipid profiles, including high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I, in this relationship.
Main Methods:
- Utilized Mendelian randomization (MR) with genome-wide association study data from 500,000 European ancestry participants (FinnGen and UK Biobank).
- Employed bidirectional MR for causality assessment, with inverse variance weighted (IVW) method as the primary analysis.
- Conducted sensitivity analyses using weighted median, MR-Egger, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) to ensure robustness of findings.
Main Results:
- Genetically predicted hypothyroidism was associated with a significant increase in CHD risk (OR = 1.078, P = .003).
- Hypothyroidism showed an inverse association with high-density lipoprotein cholesterol (HDL-C) (β = -0.013, P = .005) and apolipoprotein A-I levels (β = -0.014, P = .008).
- Lower HDL-C (OR = 0.734, P < .001) and apolipoprotein A-I (OR = 0.845, P < .001) were independently associated with increased CHD risk.
Conclusions:
- Established a causal link between hypothyroidism and elevated CHD risk, mediated by dysregulation of HDL-C and apolipoprotein A-I.
- Emphasizes the clinical importance of monitoring lipid profiles in patients with hypothyroidism.
- Suggests further research into these mechanistic pathways for improved cardiovascular disease management.
Context:
Hypothyroidism's role in coronary heart disease (CHD) and its link with lipid metabolism is debated. Our study aims to clarify the causal relationship between hypothyroidism and CHD, focusing on the potential mediating effects of lipid profiles.
Objective:
To assess the causal effect of hypothyroidism on the development of CHD and examine the mediating role of lipid profiles through Mendelian randomization (MR).
Methods:
We conducted MR tests using genome-wide association study data of 500 000 participants of European ancestry from FinnGen and UK Biobank, respectively. Bidirectional MR tests were utilized to confirm causality, and the results of an inverse variance weighted method served as the main analysis. Weighted median, MR-Egger, and MR-Pleiotropy Residual Sum and Outlier methods were utilized as sensitivity analyses to validate our findings.
Results:
We found genetically predicted hypothyroidism increased the risk of CHD by 7.8% [odds ratio (OR) = 1.078, 95% confidence interval (CI) 1.026-1.134, P = .003]. This liability was also inversely associated with high-density lipoprotein cholesterol (HDL-C) levels (β = -0.013, 95% CI -0.022-0.004, P = .005) and apolipoprotein A-I levels (β = -0.014, 95% CI -0.025-0.004, P = .008). HDL-C was inversely associated with coronary heart disease (OR 0.734, 95% CI 0.670-0.803, P < .001), and apolipoprotein A-I was also inversely associated with coronary heart disease (OR 0.845, 95% CI 0.768-0.931, P < .001).
Conclusion:
Our findings suggested a causal link between hypothyroidism and increased CHD risk, likely mediated through changes in HDL-C and apolipoprotein A-I levels. This highlights the importance of monitoring lipid levels in hypothyroid patients and calls for further research to explore these relationships and their implications for prevention and treatment strategies.
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