Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling

Vliet, Nicolien A. van; Bos, Maxime M.; Thesing, Carisha S.; Chaker, Layal; Pietzner, Maik; Houtman, E.; Neville, Matt J.; Li‐Gao, Ruifang; Trompet, Stella; Mustafa, Rima; Ahmadizar, Fariba; Beekman, Marian; Bot, Mariska; Budde, Kathrin; Christodoulides, Constantinos; Dehghan, Abbas; Delles, Christian; Elliott, Paul; Evangelou, Marina; Gao, He; Ghanbari, Mohsen; Herwaarden, Antonius E. van; Ikram, M. Arfan; Jaeger, Martin; Jukema, J. Wouter; Karaman, Íbrahím; Karpe, Fredrik; Kloppenburg, Margreet; Meessen, Jennifer; Meulenbelt, Ingrid; Milaneschi, Yuri; Mooijaart, Simon P.; Mook‐Kanamori, Dennis O.; Netea, Mihai G.; Netea‐Maier, Romana T.; Peeters, Robin P.; Penninx, Brenda W. J. H.; Sattar, Naveed; Slagboom, P. Eline; Suchiman, H. Eka D.; Völzke, Henry; Dijk, Ko Willems van; Noordam, Raymond; Heemst, Diana van

doi:10.1186/s12916-021-02130-1

Cited by 19 publications

(11 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypothyroidism has a different impact on blood lipid profiles. A higher degree of ApoB-containing lipoprotein cholesterols is found in patients with TSH >10 mLU/L compared to those with TSH 4.0–10.0 mLU/L ( 17 , 18 , 19 ). Regardless of the thyroid status, circulating TSH level is always positively correlated with levels of ApoB-containing lipoprotein cholesterols ( 20 , 21 , 22 , 23 , 24 , 25 ).…”

Section: Dyslipidemia In Hypothyroidismmentioning

confidence: 89%

Update on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism

Liu

Peng

2022

Endocrine Connections

View full text Add to dashboard Cite

Hypothyroidism is often associated with elevated serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides. Thyroid hormone (TH) affects the production, clearance and transformation of cholesterol, but current research shows that thyroid-stimulating hormone (TSH) also participates in lipid metabolism independently of TH. Therefore, the mechanism of hypothyroidism-related dyslipidemia is associated with the decrease of TH and the increase of TSH levels. Some newly identified regulatory factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiogenin-like proteins (ANGPTL), and fibroblast growth factors (FGF) are the underlying causes of dyslipidemia in hypothyroidism. High-density lipoprotein (HDL) serum concentration changes were not consistent, and its function was reportedly impaired. The current review focuses on the updated understanding of the mechanism of hypothyroidism-related dyslipidemia.

show abstract

Section: Dyslipidemia In Hypothyroidismmentioning

confidence: 89%

Update on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism

Liu

Peng

2022

Endocrine Connections

View full text Add to dashboard Cite

show abstract

“…According to Wang et al 17 , per 1 standard deviation (SD) increase in normal TSH was significantly associated with a 0.048 SD increase in TC and a 0.032 SD increase in LDL-C, whereas TSH did not show a causal association with HDL-C and TGs. The study by van Vliet et al 18 unveiled a positive association between high TSH within normal range with the levels of very low-density lipoprotein subclasses and components, TGs, and the TG contents in lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Age-specific serum thyrotropin reference range for the diagnosis of subclinical hypothyroidism and its association with lipid profiles in the elderly population

Zhang

Wang

et al. 2022

Sci Rep

View full text Add to dashboard Cite

The overdiagnosis of subclinical hypothyroidism (SCH) in the elderly has driven researchers to establish age-specific thyroid stimulating hormone (TSH) intervals to precisely evaluate the prevalence of SCH. Moreover, abnormal lipid profiles, an insidious manifestation of SCH, show various impacts on different age groups. This study aimed to establish an age-specific TSH reference range to clarify the spectrum of SCH in the elderly. The prevalence of dyslipidemia and the age-specific association between TSH and lipid profiles were analyzed to elucidate the relationship between SCH and dyslipidemia. This cross-sectional study enrolled 2460 participants aged ≥ 65 years via cluster sampling. All participants received physical, laboratory tests and thyroid ultrasound examination and completed the questionnaire. The chi-square test was used to analyze variations of dyslipidemia prevalence among different groups. The Cochran-Armitage trend test was applied for testing the linear trends of age-specific prevalence of dyslipidemia among different TSH intervals in each age group. After adjusting for confounding factors, the age-specific association between TSH and lipid profiles was identified using multi-variate linear regression analysis. The TSH reference ranges in the 65–70 age group, 71–80 age group and > 80 age group were 0.65–5.51 mIU/L, 0.85–5.89 mIU/L and 0.78–6.70 mIU/L, respectively. Using these age-specific reference ranges, the prevalence of SCH in the whole population was 3.74%, which was significantly lower than the prevalence based on the laboratory reference range (10.28%). In the 65–70 age group, only the prevalence of high total cholesterol (TC) increased significantly with the age-specific TSH intervals, and TSH was positively associated with TC and low-density lipoprotein cholesterol (LDL-C). In the 71–80 and > 80 age groups, the prevalence of high TC, high triglycerides (TGs), and high LDL-C increased significantly with elevated TSH reference ranges. The levels of TC, TGs, and LDL-C were also positively associated with TSH level in 71–80 age group. However, such an association disappeared in > 80 age group. An age-specific reference range for TSH can effectively prevent the overdiagnosis of SCH in the elderly. Aging could somewhat attenuate the impact of TSH on lipid profiles.

show abstract

“…Considering the existing evidence linking lipids to thyroid function and thyroid diseases, as documented in prior studies ( 2 , 3 , 5 ), to investigate whether the association between genetic proxies of lipid-lowering drugs and thyroid dysfunction risk was independent of lipid-lowering effect, we additionally assessed the potential association between LDL-C and TG levels and the risk of thyroid dysfunction, as well as their association with thyroid function traits by using genome-wide significant variants characterized by low pairwise correlations (threshold r 2 < 0.001).…”

Section: Methodsmentioning

confidence: 99%

Genetic insights into repurposing statins for hyperthyroidism prevention: a drug-target Mendelian randomization study

Huang,

Wu,

Lin

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundCurrent therapeutic measures for thyroid dysfunction are limited and often accompanied by adverse effects. The use of lipid-lowering drugs like statins has recently been associated with lower thyroid eye diseases risk.ObjectiveTo investigate the implications of genetically proxied lipid-lowering drugs on thyroid dysfunction.MethodsIn this drug-target Mendelian randomization (MR) study, we utilized genetic variants within drug target genes associated with low-density lipoprotein (LDL) or triglyceride (TG), derived from a genome-wide association study (GWAS) meta-analysis (N ≤ 188,577), to simulate lifelong drug interventions. Genetic summary statistics for thyroid dysfunction outcomes were retrieved from GWAS datasets of Thyroid Omics Consortium (N ≤ 54,288) and UK Biobank (N = 484,598). Inverse-variance-weighted MR (IVW-MR) method was performed as primary analysis, followed by validation in colocalization analysis. A subsequent two-step MR analysis was conducted to identify biomarkers mediating the identified drug-outcome association.ResultsIn IVW-MR analysis, genetic mimicry of 3-hydroxy-3-methylglutarylcoenzyme reductase (HMGCR) inhibitors (e.g. statins) was significantly associated with lower risk of hyperthyroidism in two independent datasets (OR1, 0.417 per 1-mmol/L lower in LDL-C; 95% CI 0.262 to 0.664; P1 = 2.262 × 10-4; OR2 0.996; 95% CI 0.993-0.998; P2 = 0.002). Two-step MR analysis revealed eighteen biomarkers linked to genetic mimicry of HMGCR inhibition, and identified insulin-like growth factor 1 (IGF-1) levels mediating 2.108% of the negative causal relationship between HMGCR inhibition and hyperthyroidism.ConclusionThis study supports HMGCR inhibition as a promising therapeutic strategy for hyperthyroidism and suggests its underlying mechanisms may extend beyond lipid metabolism. Further investigations through laboratory studies and clinical trials are necessary to confirm and elucidate these findings.

show abstract

Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling

Cited by 19 publications

References 64 publications

Update on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism

Update on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism

Age-specific serum thyrotropin reference range for the diagnosis of subclinical hypothyroidism and its association with lipid profiles in the elderly population

Genetic insights into repurposing statins for hyperthyroidism prevention: a drug-target Mendelian randomization study

Contact Info

Product

Resources

About