Aging: Sex differences in major cardiovascular outcomes and fractures in patients with subclinical thyroid dysfunction

Background: Subclinical thyroid dysfunction (STD) is common in the adult population and is characterized by asymptomatic, abnormal thyroid-stimulating hormone (TSH) levels, and normal
levels of free thyroid hormone and free triiodothyronine.
The prevalence of subclinical hypothyroidism (SH) ranges from 4.
0% to 20.
0%, and the prevalence of subclinical hyperthyroidism (SCH) varies
from 0.
7% to 9.
0%.
Given the low rate of STD progression in older adults over a 5-year period (<0.
5%) and the limited amount of evidence that early treatment can alter the clinical course, the optimal treatment for STDs is controversial
.
Investigating the potential impact of STDs on long-term adverse health outcomes will help guide clinical treatment
in high-risk populations.

Previous studies have addressed long-term adverse health outcomes for STD patients, including cardiovascular disease, stroke, all-cause mortality, chronic kidney disease, cognitive decline, decreased bone density, and fractures
.
These studies have found that STDs are associated
with an increased risk of long-term adverse health outcomes.
The sex association between STDs and long-term adverse health outcomes remains unclear
.

Objective: Given the few reports of sex-related differences in the association of subclinical SH and SCH with chronic kidney disease, cognitive decline, and decreased bone mineral density, we conducted a systematic review and meta-analysis to assess differences in STDs associated with major adverse cardiovascular events (MACEs) and fractures between men and women
.

Methods: Eligible studies
from initial to November 2021 were searched in the databases of PubMed, EMBASE and Cochrane Libraries.
Relative risk ratios (RR) and 95% confidence intervals (CI) were used to determine sex differences
between SH and SCH and MACE and fracture risk.
All analyses were performed
using a random-effects model.

Results: Twenty-four cohort studies (3,480,682 patients) entered meta-analysis
.
There was no sex difference
between SH and Sch and the risk of atrial fibrillation, all-cause mortality, cardiogenic death, coronary heart disease, heart failure, Mace, stroke, and fracture.
Subgroup analysis showed that men with SH had a higher risk of MACE than women (RR 2.
44; 95% confidence interval 1.
17 to 5.
10; P = 0.
017)
if follow-up was followed for ≥10.
0 years 。 If the follow-up period was < 10.
0 years (RR 1.
17 years, 95% confidence interval 1.
03~1.
34; P=0.
017), men had a higher risk of any fracture than women (RR 1.
17 years; 95% confidence interval 1.
03~1.
34 years; P=0.
017), and the degree of study adjustment was high (RR 1.
16 years; 95% confidence interval 1.
02~1.
32 years; P=0.
022)
。 However, the risk of hip fracture was lower in men than in women after combining low-adjustment studies (RR 0.
53; 95% confidence interval 0.
29 to 0.
97; P = 0.
039).

Figure 1 Pooled results
stratified by sex in the relationship between subclinical thyroid dysfunction and atrial fibrillation, all-cause mortality, cardiogenic death, coronary heart disease, heart failure, major adverse cardiovascular events, and stroke risk.

Table 1 Gender differences
in long-term health outcomes in patients with subclinical thyroid dysfunction.

Table 2 Sensitivity analysis
for direct comparison of sex differences in long-term health outcomes in patients with subclinical thyroid dysfunction.

Figure 2 Pooled results
stratified by sex in the correlation between subclinical thyroid dysfunction and the risk of any fracture, hip fracture, non-vertebral fracture, and vertebral fracture.

Conclusions: There may be sex differences
in the risk of developing MACE, any fracture, and hip fracture in patients with SH.

Fang H, Zhao R, Cui S, Wan W, Sex differences in major cardiovascular outcomes and fractures in patients with subclinical thyroid dysfunction: a systematic review and meta-analysis Aging (Albany NY) 2022 Oct 25; 14