Hypothyroidism And The Risk Of Stroke: A Meta-analysis

Background and ObjectiveStroke is the first leading cause of death in China.According to the Global Burden of Disease Study 2016,the prevalence and incidence of stroke is steadily increased in China,the disease burden caused by stroke is still very serious.In recent years,existing studies provide evidence that thyroid dysfunction is associated with the risk of cerebrovascular disease.Hypothyroidism is a common kind of thyroid dysfunction,it refers to thyroid hormone deficiency and the other causes can lead to a decreased general metabolic function.Hypothyroidism can be classified as overt hypothyroidism(OHypo)or subclinical hypothyroidism(SCH)by its severity.OHypo is characterisitc as free thyroxine concentrations below the reference range and thyroids-timulating hormone(TSH)concentrations above the reference range.While SCH is defined by free thyroxine concentrations within the normal range but TSH concentrations above the reference range.The prevalence of hypothyroidism in adult population varies between 5%and 10%.Hypothyroidism is increasing in incidence with age and arising more frequently in elderly women.SCH is more common than OHypo.There are evidence that hypothyroidism is associated with hyperlipidemia,atherosclerosis,diabetes,homocysteine,a high level of C-response protein,increased carotid intimal media thickness,hypertension and coronary heart disease,which are the risk factors of stroke.At present,there is still a great debate about whether hypothyroidism increases the risk of stroke.The purpose of this study is to evaluate the correlation between the risk of stroke and hypothyroidism by using a method of meta-analysis.MethodsPublished case-control studies and cohort studies were identified through a systematic search through Pubmed database,The Cochrane Library,Web of Science database,Medline database,Google Scholar,EMBASE database,CNKI,Wanfang and VIP database.By two independent reviewers to screen articles according to the inclusion criteria and exclusion criteria,and then extract the data.Outcome events include stroke,OR or RR or HR and its 95%CI of the association between hypothyroidism and the risk of stroke were provided.Quality assessment using the Newcastle-Ottawa scale(NOS)for included studies.The statistical software Stata12.0 was used for data analysis,I~2 statistic was measured and the Q-statistic was tested to assess heterogeneity across studies.If the heterogeneity was high,meta-regressions model were set,then univariate and multivariate meta-regression analyses were conducted to explore potential sources of heterogeneity combined with subgroup analyses and sensitivity analyses.Publication bias was identified visually by funnel plots and evaluated statistically with an Egger test.Results(1)A total of 11 studies met the criteria were involved totally,including 1case-control study and 10 cohort studies.The included studies provided information on total of 238,916 participants(including 43,888 cases of hypothyroidism)with6,026 stroke events.The pooled risk ratio(RR)for participants with hypothyroidism compared to euthyroid group was 1.27(95%CI 1.03~1.55)for stroke events.(2)Univariate meta-regression analyses indicated that study type,region and mean age may be the major sources of heterogeneity.The result of multivariate meta-regression analyses applied to mean age,study type and region indicated that Tau-squared among studies decreased from 0.0635 to 0.0053,which can explain91.6%of the heterogeneity.(3)Subgroup analyses showed that mean age less than 65 years individuals with hypothyroidism had a higher risk of stroke(RR=1.52,95%CI 1.07~2.16)compared with euthyroid group,but there was higher heterogeneity.Subclinical hypothyroidism may not increase the risk of stroke(RR=1.09,95%CI 0.92~1.29).The studies from America had higher heterogeneity than Europe and Asia subgroups,there was no statistically significant between patients with hypothyroidism among American and the risk of stroke.Region may be one of the sources of heterogeneity.(4)The results were robust and reliable indicated by sensitivity analysis and publication bias.Conclusions(1)Patients with hypothyroidism had a higher risk of stroke compared with euthyroidism.Hypothyroidism may be a risk factor of stroke.(2)Patients with average age less than 65 years in hypothyroidism had a higher risk of stroke.(3)Subclinical hypothyroidism may not increase the risk of stroke.