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Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations
Published on: July 21, 2023
Plasma TSH and cardiovascular disease in the general population: A Mendelian randomization study of 105,224
Nawar Dalila1, Ruth Frikke-Schmidt2, Børge G Nordestgaard3
1Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Denmark.
Insights
Low thyroid stimulating hormone (TSH) levels are linked to increased cardiovascular disease risk, including atrial fibrillation and myocardial infarction. These associations appear to be causal, highlighting TSH as a potential factor in heart health.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Genetics
Background:
- Cardiovascular disease risk is often assessed using clinical disease categories.
- The continuous relationship between thyroid stimulating hormone (TSH) and cardiovascular events requires further investigation.
Purpose of the Study:
- To determine if TSH, on a continuous scale, is associated with the risk of various cardiovascular diseases.
- To investigate whether these observed associations between TSH and cardiovascular disease are likely to be causal.
Main Methods:
- Prospective cohort study of 105,224 individuals from the Copenhagen General Population Study.
- Analysis of observational associations between plasma TSH and incident cardiovascular events.
- Utilized genetic risk scores and Mendelian randomization to assess causality.
Main Results:
- Lower TSH concentrations were associated with a higher risk of atrial fibrillation, myocardial infarction, stroke, heart failure, aortic valve stenosis, and major adverse cardiovascular events.
- Individuals with TSH at the 5th percentile or lower had significantly increased hazard ratios for stroke and heart failure compared to those above the 50th percentile.
- Genetic risk estimates indicated a potential causal link between lower TSH and increased risk of atrial fibrillation, myocardial infarction, and aortic valve stenosis.
Conclusions:
- Low plasma TSH levels are associated with an increased risk of atrial fibrillation, myocardial infarction, and aortic valve stenosis in the general population.
- Both observational and genetic analyses suggest these associations may reflect causal pathways.
- TSH may play a direct role in the development of specific cardiovascular diseases.
Background And Aims:
The association between thyroid stimulating hormone (TSH) and cardiovascular disease has mainly been determined using clinical categories of disease. We tested the hypothesis that TSH on a continuous scale is associated with risk of atrial fibrillation (AF), myocardial infarction (MI), stroke, heart failure (HF), aortic valve stenosis (AVS), and major adverse cardiovascular events (MACE) and whether these associations are likely to be causal.
Methods:
We first tested whether plasma TSH on a continuous scale was observationally associated with incident cardiovascular events in a prospective cohort study of 105,224 individuals from the Copenhagen General Population Study followed for a median 7 years. Next, we tested whether a genetic risk score weighted on TSH was associated with cardiovascular endpoints. Finally, using Mendelian randomization, we tested whether the observed associations were likely to be causal.
Results:
Using restricted cubic splines, lower concentrations of TSH relative to the population median (=1.53 mIU/L) were associated with higher risk of AF, MI, stroke, HF, AVS, and MACE. Comparing individuals with TSH ≤5th percentile (≤0.54 mIU/L) versus >50th percentile (>1.53 mIU/L), hazard ratios (HRs) ranged from 1.12 (1.00-1.26) for stroke to 1.27 (1.11-1.46) for HF. Genetic risk estimates per standard deviation decrease in TSH were 1.28 (1.08-1.52) for AF, 1.35 (1.06-1.71) for MI, 1.06 (0.89-1.26) for stroke, 1.19 (0.94-1.52) for HF, 1.53 (1.03-2.26) for AVS, and 1.09 (0.97-1.23) for MACE.
Conclusions:
In 105,224 individuals from the general population low plasma TSH was observationally and genetically associated with increased risk of AF, MI, and AVS suggesting that these observations may reflect causal pathways.
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