Role of thyroid hormone in ischemic heart disease.

1. Budha Ratna Rav
(Int-phd biology)

2. Overview
• Role of Pituitary gland
• Thyroid axis of pituitary interacts with gonadal axis
• Role of the hormones in the ischemic heart disease or Coronary
Artery disease
• Mendelian randomization
• Conclusion of paper

3. Role of Pituitary gland
3

4. Thyroid axis of pituitary interacts with
gonadal axis.

5. Contraction of heart muscles

6. 6
Exactly what is Coronary Artery Disease
(Ischemic Heart Disease) and how/why does it
occur?

7. Studies in the paper
• Men have higher rates of IHD than women at the same established
risk factor
• Lower the growth hormone / IGF lower risk of chorionic disease
• Suppressing the reproductive axis increase the life span
• TPOAbs have key role in the synthesis of thyroid hormones
• Thyroid hormones involved in the testicular development of animals
• Thyroid peroxidase antibody play role in the synthesis of thyroid
hormones and also associated with higher risk of CVD events.

8. Continue….
• A meta- analysis of cohort studies , Higher and lower TSH both
associated with higher risk of CVD events.
• Randomized control trials shows that administration of levothyroxine
lowers the TSH via negative feedback
• SNP for the genes of TSH, FT4, TPOAb are show potentially pleiotropic
effect on IHD.

9. Role of GH,TSH, FT4, TPOAb positivity
• Lower growth hormone are associated with lower risk of IHD.
• Higher TSH is associated with higher total cholesterol.
• FT4 regulated the TSH via negative feedback.
e.g. Levothyroxine injected, lower the TSH and total cholesterol.
• TPOAb help in the synthesis of thyroid hormone and associated with
IHD.

10. MENDELIAN RANDOMIZATION
Method that use in the variation in genes of known function to
examine the casual effects of modifiable exposure on disease in
observational studies.
ASSUPTIONS TAKING IN THE STUDY
1) Blood pressure was not included in the study.
2)Studies was limited to the Caucasians populations.
3) Large sample size required.
4) Use of separate sample analysis, we assessed the role of SNPs of TSH
and FT4 are same on CAD

11. DATA OBATAINED
• Genetic predictors(SNPs) for TSH and FT4, were obtained from a large
meta-analysis of GWAS (n = 26,420(for TSH) and n = 17,520 for (FT4)
of European descent from 15 cohorts (mean age 42.5 to 79.0 years
old), which excluded people taking thyroid medication, with thyroid
surgery, or with TSH values outside the normal range.
• Genetic predictors for TSH were also obtained from a large whole-
genome sequencing study of the Icelandic population (n = 2,636),
mean age 55 years old, with genetic associations adjusted for age and
sex48.

12. Continue…..
• Genetic predictors for TPOAb positivity were obtained from a large
meta-analysis of GWAS in general population in 18,297 Caucasians
from 11 studies (mean age 46.9 to 74.8 years old), with genetic
associations adjusted for age and sex22.
• Genetic associations with lipids (as inverse normal transformed effect
sizes), including HDL-cholesterol, LDL-cholesterol and triglycerides,
adjusted for age, age2 and sex, were obtained from the Global Lipids
Genetics Consortium Results
(http://csg.sph.umich.edu//abecasis/public/lipids2013/), with
188,577 participants of European descent and 7,898 participants of
non-European descent, mean age 55.2 years old59.

13. CONCLUSIONS
• This novel study provides little indication that TSH, FT4 or TPOAb
positivity affects IHD.
• the expression of IGFBP2 and IGFBP5 relates to the growth
hormone/IGF systems, which is associated with risk of major chronic
diseases in genetic studies.
• Genetically predicted TSH, FT4 and TPOAb positivity were not
associated with risk of CAD/MI when potentially pleiotropic SNPs
were excluded.
• Testosterone have positive effect on IHD.

14. Question please ?

15. Thank You