Relationship between Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.
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ABSTRACT: Background
Evidence on the association between subclinical thyroid dysfunction and the risk of cardiovascular outcomes are conflicting.Methods and results
PubMed, EMbase, Web of Science, Cochrane Library, and China Biology Medicine (CBM) databases were searched from inception to July 10, 2016. A total of 16 studies were included for meta-analysis. We found that subclinical hypothyroidism was not correlated with coronary heart disease (CHD) (RR?=?1.17; 95% CI, 0.91-1.52), total mortality (RR?=?1.02; 95% CI, 0.93-1.13), cardiovascular mortality (RR?=?1.06; 95% CI, 0.77-1.45), heart failure (RR?=?1.17; 95% CI, 0.87-1.57), and atrial fibrillation (RR?=?1.05; 95% CI, 0.91-1.21), except CHD mortality (RR?=?1.37; 95% CI, 1.03-1.84). Subgroup analysis indicated a higher estimation risk in CHD (RR?=?1.54; 95% CI, 1.00-2.39), cardiovascular mortality (RR?=?2.14; 95% CI, 1.43-3.22), and CHD mortality (RR?=?1.54; 95% CI, 1.11-2.15) among participants?ConclusionsSubclinical hypothyroidism is likely associated with an increased risk of CHD mortality, and subclinical hyperthyroidism is likely associated with increased risk of CHD, CHD mortality, and total mortality.
SUBMITTER: Sun J
PROVIDER: S-EPMC5610794 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Relationship between Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.
Sun Jing J Yao Liang L Fang Yuan Y Yang Ruifei R Chen Yaolong Y Yang Kehu K Tian Limin L Tian Limin L
International journal of endocrinology 20170831
<h4>Background</h4>Evidence on the association between subclinical thyroid dysfunction and the risk of cardiovascular outcomes are conflicting.<h4>Methods and results</h4>PubMed, EMbase, Web of Science, Cochrane Library, and China Biology Medicine (CBM) databases were searched from inception to July 10, 2016. A total of 16 studies were included for meta-analysis. We found that subclinical hypothyroidism was not correlated with coronary heart disease (CHD) (RR = 1.17; 95% CI, 0.91-1.52), total mo ...[more]
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Project description:CONTEXT:Although both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting. OBJECTIVE:This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts. DATA SOURCES:We searched in MEDLINE and EMBASE from inception until November 2014. STUDY SELECTION:Two physicians identified prospective cohorts that assessed thyroid function and cognitive outcomes (dementia; Mini-Mental State Examination [MMSE]). DATA EXTRACTION:Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. The primary outcome was dementia and decline in cognitive function was the secondary outcome. DATA SYNTHESIS:Eleven prospective cohorts followed 16,805 participants during a median followup of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (SHyper) (n = 6410), six in subclinical hypothyroidism (SHypo) (n = 7401). Five studies analyzed MMSE decline in SHyper (n = 7895), seven in SHypo (n = 8960). In random-effects models, the pooled adjusted risk ratio for dementia in SHyper was 1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval, 0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant heterogeneity (I2 = 0.0%). The pooled mean MMSE decline from baseline to followup (mean 32 mo) did not significantly differ between SHyper or SHypo vs euthyroidism. CONCLUSIONS:SHyper might be associated with an elevated risk for dementia, whereas SHypo is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed.
| S-EPMC6287525 | biostudies-literature
Project description:IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.Methods and analysisWe will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal.Prospero registration numberCRD42018091627.
| S-EPMC6661665 | biostudies-literature
Project description:In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.
| S-EPMC7644764 | biostudies-literature
Project description:ObjectiveTo evaluate whether sex differences in the associations of subclinical hypothyroidism (SH) and subclinical hyperthyroidism (SCH) with the risks of major adverse cardiovascular events (MACE) and fractures.MethodsThe PubMed, EmBase, and Cochrane Library databases were searched for eligible studies from inception until November 2021. The relative risk (RR) ratio with the 95% confidence interval (CI) was used to identify sex differences in the associations of SH and SCH with the risks of MACE and fractures. All analyses were performed using a random-effects model.ResultsTwenty-four cohort studies (in 3,480,682 patients) were selected for meta-analysis. There were no sex differences in the associations of SH and SCH with the risks of atrial fibrillation, all-cause mortality, cardiac death, coronary heart disease, heart failure, MACE, stroke, fracture. Subgroup analyses indicated a greater risk of MACE in men than in women with SH if follow-up was ≥10.0 years (RR ratio 2.44; 95% CI 1.17-5.10; P = 0.017). The risk of any fracture was greater in men than in women with SH if follow-up was <10.0 years (RR ratio 1.17; 95% CI 1.03-1.34; P = 0.017) and in studies with a high level of adjustment (RR ratio 1.16; 95% CI 1.02-1.32; P = 0.022). However, the risk of hip fracture was lower in men than in women with SH on pooling of studies with low adjustment (RR ratio 0.53; 95% CI 0.29-0.97; P = 0.039).ConclusionsThere may be sex-related differences in the risks of MACE, any fracture, and hip fracture in patients with SH.
| S-EPMC9648794 | biostudies-literature
Project description:IMPORTANCE:Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE:To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION:The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION:Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ?4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES:The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS:Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE:Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.
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Project description:ObjectiveThyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes.MethodsIn total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45-4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45-60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke.ResultsMean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24-1.07) comparing subclinical hyperthyroidism and 0.90 (0.58-1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism).ConclusionsIn this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.
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Project description:BACKGROUND:The effects of thyroid dysfunction in patients with preexisting heart failure have not been adequately studied. We examined the prevalence of thyroid dysfunction and associations with cardiovascular outcomes in a large, prospective cohort of outpatients with preexisting heart failure. METHODS AND RESULTS:We examined associations between thyroid dysfunction and New York Heart Association class, atrial fibrillation, and a composite end point of ventricular assist device placement, heart transplantation, or death in 1365 participants with heart failure enrolled in the Penn Heart Failure Study. Mean age was 57 years, 35% were women, and the majority had New York Heart Association class II (45%) or III (32%) symptoms. More severe heart failure was associated with higher thyroid-stimulating hormone (TSH), higher free thyroxine (FT4), and lower total triiodothyronine (TT3) concentrations ( P<0.001 all models). Atrial fibrillation was positively associated with higher levels of FT4 alone ( P?0.01 all models). There were 462 composite end points over a median 4.2 years of follow-up. In adjusted models, compared with euthyroidism, subclinical hypothyroidism (TSH 4.51-19.99 mIU/L with normal FT4) was associated with an increased risk of the composite end point overall (hazard ratio, 1.82; 95% CI, 1.27-2.61; P=0.001) and in the subgroup with TSH ?7.00 mIU/L (hazard ratio, 3.25; 95% CI, 1.96-5.39; P<0.001), but not in the subgroup with TSH 4.51-6.99 mIU/L (hazard ratio, 1.26; 95% CI, 0.78-2.06; P=0.34). Isolated low T3 was also associated with the composite end point (hazard ratio, 2.12; 95% CI, 1.65-2.72; P<0.001). CONCLUSIONS:In patients with preexisting heart failure, subclinical hypothyroidism with TSH ?7 mIU/L and isolated low T3 levels are associated with poor prognosis. Clinical trials are needed to explore therapeutic effects of T4 and T3 administration in heart failure.
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Project description:BackgroundDiabetes mellitus and thyroid disease are two areas of broad interest in the field of endocrinology and metabolism. Variation of thyroid hormone concentration, even within the normal range, may portend the onset of type 2 diabetes mellitus (T2DM), especially among those with prediabetes. However, current evidence is mixed.MethodsProspective studies which assessed diabetes incidence were identified using a database search of MEDLINE and Embase through May 1, 2021. The Sidik-Jonkman random-effects model and cubic spline model were used to evaluate the associations and dose-response relationships between thyroid function/hormone levels and risk of T2DM and cardiovascular disease (CVD) risk among T2DM patients.ResultsA total of 12 prospective studies were included. We found that high baseline TSH levels were related to a 17% higher risk of T2DM (RR 1.17, 95% CI 1.01, 1.36; I2=78%, P<0.01), compared with normal TSH levels. Low FT3 (RR 1.40, 95% CI 1.09, 1.80; I2=59%, P=0.03) and low FT4 (RR 1.33, 95% CI 1.04, 1.71; I2=62%, P=0.02) levels were significantly associated with risk of T2DM. The cubic spline model indicated a J-shaped relationship with TSH, but inverted-J-shaped relationships with FT3 and FT4. CVD events and all-cause deaths were prospectively evaluated in four studies, but were not associated with abnormal thyroid function.ConclusionsOur meta-analysis determined that abnormal thyroid hormone level is associated with an increased risk of T2DM, showing a J-shaped relationship with TSH and inverted-J-shaped relationships with FT3 and FT4.Trial registrationRegistered number in PROSPERO: CRD42021225695 .
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Project description:Background: Vegetarian dietary patterns are recommended for cardiovascular disease (CVD) prevention and management due to their favorable effects on cardiometabolic risk factors, however, the role of vegetarian dietary patterns in CVD incidence and mortality remains unclear. Objective: To update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we undertook a systematic review and meta-analysis of the association of vegetarian dietary patterns with major cardiovascular outcomes in prospective cohort studies that included individuals with and without diabetes using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Methods: MEDLINE, EMBASE, and Cochrane databases were searched through September 6th, 2018. We included prospective cohort studies ≥1 year of follow-up including individuals with or without diabetes reporting the relation of vegetarian and non-vegetarian dietary patterns with at least one cardiovascular outcome. Two independent reviewers extracted data and assessed study quality (Newcastle-Ottawa Scale). The pre-specified outcomes included CVD incidence and mortality (total CVD, coronary heart disease (CHD) and stroke). Risk ratios for associations were pooled using inverse variance random effects model and expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I 2-statistic). The overall certainty of the evidence was assessed using GRADE. Results: Seven prospective cohort studies (197,737 participants, 8,430 events) were included. A vegetarian dietary pattern was associated with reduced CHD mortality [RR, 0.78 (CI, 0.69, 0.88)] and incidence [0.72 (0.61, 0.85)] but were not associated with CVD mortality [0.92 (0.84, 1.02)] and stroke mortality [0.92 (0.77, 1.10)]. The overall certainty of the evidence was graded as "very low" for all outcomes, owing to downgrades for indirectness and imprecision. Conclusions: Very low-quality evidence indicates that vegetarian dietary patterns are associated with reductions in CHD mortality and incidence but not with CVD and stroke mortality in individuals with and without diabetes. More research, particularly in different populations, is needed to improve the certainty in our estimates. Clinical Trial Registration: Clinicaltrials.gov, identifier: NCT03610828.
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Project description:High protein diets have gained increased popularity as a means of losing weight, increasing muscle mass and strength, and improving cardiometabolic parameters. Only a few meta-analyses have addressed their impact on cardiovascular morbidity and mortality and failed to show any significant associations without applying strict values to define high protein intake. Due to the conflicting research background, we conducted a meta-analysis to assess the impact of high protein diets compared to normal protein consumption on cardiovascular outcomes in adults without established cardiovascular disease. Fourteen prospective cohort studies were included. A total of 6 studies, including 221,583 participants, reported data about cardiovascular death, without showing a statistically significant difference in the random effect model (odds ratio: 0.94; confidence interval: 0.60-1.46; I2 = 98%; p = 0.77). Analysis of three studies, which included 90,231 participants showed that a high protein diet was not associated with a lower risk of stroke (odds ratio: 1.02; confidence interval: 0.94-1.10; I2 = 0%; p = 0.66). Regarding the secondary outcome of non-fatal myocardial infarction, stroke, or cardiovascular death, 13 studies that included 525,047 participants showed no statistically significant difference (odds ratio; 0.87; confidence interval: 0.70-1.07; I2 = 97%; p = 0.19). In conclusion, according to our study results, high protein consumption does not affect cardiovascular prognosis.
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