Background Growth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor β cytokine superfamily. Some evidence support that it’s involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it’s still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence. Methods Genetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses. Results Among 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. Conclusions The MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.
BackgroundGlobal and national estimates on the epidemiology of aortic aneurysms are prerequisites for disease management and policymaking. Based on the Global Burden of Disease (GBD) 2019, this study aimed to discern the global aortic aneurysm burden by systematically analyzing demographic data on mortality and exploring the attributable risks and relevant factors.MethodsThe data analyzed in this study were available in the Global Health Data Exchange (GHDx) online query tool. The population in our study comprised individuals from 204 countries and territories from 1990 to 2019. The estimated annual percentage changes (EAPCs) were performed to assess the temporal trends of aortic aneurysms and their attributable risks. Spearman correlation analysis was performed to explore the relationship between the burden of aortic aneurysm and covariates.ResultsAlthough aortic aneurysm-related deaths (82.1%) and disability-adjusted life years (DALYs) (67%) increased from 1990 to 2019, the global trend of age-standardized rate of death (ASRD) (EAPC: −1.34, 95% CI = −1.46 to −1.22, P < 0.001) and age-standardized rate of DALY (ASDALYR) (EAPC: −1.06, 95% CI = −1.17 to −0.95, P < 0.001) decreased, both of which presented age dependence and gender differences. Smoking and high systolic blood pressure (SBP) were the main attributable risks of disease burden and tend to decease globally (EAPC: −1.89, 95% CI = −2.03 to −1.89, P < 0.001; −1.31 95% CI = −1.43 to −1.19, P < 0.001, respectively). Alcohol abstinence (male: R = −0.71, P < 0.001; female: R = −0.73, P < 0.001), smoking age of initiation (male: R = −0.32, P < 0.001; female: R = −0.50, P < 0.001), physical activity (male: R = −0.50, P < 0.001; female: R = −0.55, P < 0.001), and mean temperature (R = −0.62, P < 0.001) had negative correlation with ASRD. However, cholesterol level (male: R = 0.62, P < 0.001; female: R = 0.39, P < 0.001), body mass index (BMI) (male: R = 0.30, P < 0.001; female R = −0.01, P > 0.05), and alcohol consumption (male: R = 0.46, P < 0.001; female: R = 0.42, P < 0.001) had a positive correlation with ASRM. Besides, standard of living and medical resources positively related to burden of aortic aneurysm.ConclusionIn this study, a decreasing trend of aortic aneurysm burden was found globally, especially in advanced regions. Aged men who smoke and women who have hypertension should pay close attention to, particularly in deprived economic groups, and many approaches can be performed to reduce the burden of aortic aneurysms.
Background. Iron overload has been implicated in the pathogenesis of varicose veins (VVs). However, the association of serum iron status with other vascular diseases (VDs) is not well understood, which might be a potential target for VD prevention. This study was aimed at investigating the causal associations between iron status and VDs using the Mendelian randomization (MR) method. Methods. A two-sample MR was designed to investigate whether iron status was associated with VDs, based on iron data from a published genome-wide association study meta-analysis of 48,972 subjects of European descent and VD data obtained from the UK Biobank, including 361,194 British subjects (167,020 males and 194,174 females). We further explored whether there was sex difference in the associations between genetically predicted iron status and VDs. Results. The results demonstrated that iron status had a significant causal effect on VVs of lower extremities ( P < 0.001 ) and a potential effect on coronary atherosclerosis ( P < 0.05 for serum iron, ferritin, and transferrin saturation, respectively), but not on other VDs. Furthermore, higher iron status exerted a detrimental effect on VVs of lower extremities in both genders ( P < 0.05 ) and a protective effect on male patients with coronary atherosclerosis ( P < 0.05 for serum iron, ferritin, and transferrin saturation, respectively). Conclusions. This MR study provides robust evidence that higher iron status increases the risk of VVs of lower extremities, whereas it reduces the incidence of coronary atherosclerosis in the male population, which indicates that iron has divergent effects on vascular pathology.
BackgroundCalcific aortic valve disease (CAVD) was highly prevalent among developed countries and caused numerous deaths. Based on the Global Burden of Disease 2019, this study was designed to present comprehensive epidemiological information, attributable risks, and relevant factors.MethodsAll data were available online via the Global Health Data Exchange (GHDx). In this study, we analyzed the global incidence, prevalence, deaths, and disability-adjusted life years (DALYs) of CAVD across different regions from 1990 to 2019. We applied the estimated annual percentage changes (EAPCs) to evaluate the change trends and their attributable risks. In addition, we explored several relevant factors.ResultsFrom 1990 to 2019, the incidence cases, prevalence cases, CAVD-related deaths, and DALYs of CAVD gradually increased globally. However, the age-standardized death rate (ASDR) was relatively stable, and the age-standardized DALYs rate gradually declined during the past 30 years. Males and elderly individuals were more likely to suffer from CAVD. High systolic blood pressure (SBP) was the predominant attributable risk of disease burden that presented a global downward trend (death: EAPC = −0.68, 95% CI −0.77~−0.59, P < 0.001; DALYs: EAPC = −0.99, 95% CI −1.09 to −0.89, P < 0.001). Alcohol consumption (R = 0.79, P < 0.001), smoking prevalence (R = 0.75, P < 0.001), and calcium (R = 0.72, P < 0.001) showed a positive correlation with the age-standardized incidence rate (ASIR), whereas classic monsoon region (R = −0.68, P < 0.001) and mean temperature (R = −0.7, P < 0.001) showed a negative correlation with age-standardized incidence rate (ASIR). Besides, medical and healthcare resources presented a positive correlation with ASIR. Meanwhile, similar relationships were found in age-standardized prevalence rate (ASPR), ASDR, and age-standardized DALY rate (ASDALYR).ConclusionCAVD displays widely varied spatial distribution around the world, of which high SDI regions have the highest burdens. Age is a powerful factor and hypertension a predominant attributable risk factor. Moreover, controlling blood pressure, avoiding smoking, reducing alcohol consumption, and so on, could effectively reduce the burden of CAVD.
High polyunsaturated fatty acids (PUFAs) intake is recommended for primary and secondary prevention of cardiovascular disease (CVD). However, the association of PUFAs with blood pressure (BP) is still controversial. In the present study, two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship of PUFAs with BP, including systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). Genetic instruments and summary statistics for two-sample MR analysis were obtained from 3 large-scale genome-wide association studies (GWASs). Eight single nucleotide polymorphisms (SNPs) significantly (P < 5 × 10−8) related to 6 PUFAs were used as instrumental variables. Conventional inverse-variance weighted method was adopted to evaluate the causality of PUFAs with BP; the Weighted Median, MR-egger, and Leave-one-out method were used for sensitivity analyses. As a result, there was no evidence of a causal association between all PUFAs and SBP. In addition, arachidonic acid (AA, β = −0.04, P < .001) and eicosapentaenoic acid (EPA, β = −0.47, P = .02) were negatively associated with DBP, while linoleic acid (LA, β = 0.03, P = .005) and α-linolenic acid (ALA, β = 3.83, P < .001) were positively associated with DBP. There was no evidence of a causal relationship between either docosapentaenoic acid (DPA) or docosahexaenoic acid (DHA) with DBP. In conclusion, a genetic predisposition to plasma polyunsaturated fatty acid (PUFA) had a divergent effect on DBP, independent of SBP. It suggested that it is helpful for lower DBP level to supplemental intake of AA and EPA or promote the conversion of LA and ALA to AA and EPA respectively, which need to be further validated with randomized controlled studies.
Exercise-based cardiac rehabilitation is safe and effective for chronic heart failure (CHF) patients. The present study aimed to investigate the effects of traditional Chinese exercise (TCE) on patients with CHF and the impact of exercise types and duration. Evaluation of randomized controlled trials (RCTs) of TCE in patients with CHF published since 1997 from PubMed, Embase, Web of Science, the Cochrane Library, Chongqing VIP, Wanfang Databases, and the China National Knowledge was performed. A total of 41 RCTs, including 3209 patients with CHF, were included. It showed that TCE significantly increased 6-min walk distance (6MWD) [mean difference (MD) = 72.82 m, p < 0.001] and left ventricular ejection fraction (MD = 5.09%, p < 0.001), whereas reduced B-type natriuretic peptide (BNP) (MD = −56.80 pg/mL, p < 0.001), N-terminal pro-BNP (MD = −174.94 pg/mL, p < 0.05), and Minnesota Living with Heart Failure Questionnaire scores (MD = −11.31, p < 0.001). However, no significant difference was found in the effects of TCE on peak oxygen consumption. The increase in TCE weekly duration and program duration significantly improved 6MWD (MD = 71.91 m, p < 0.001; MD = 74.11 m, p < 0.001). The combination of TCE and conventional aerobic exercise significantly improved 6MWD (MD = 19.86 m, p < 0.005). TCE improves exercise capacity, cardiac function, and quality of life in patients with CHF, which might be an optimal and available pattern of exercise-based cardiac rehabilitation.
Background: Growth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor β (TGF-β) cytokine superfamily. Some evidence support that it’s involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it’s still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence.Methods: Genetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted (IVW) method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses.Results: Among 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy.Conclusions: The MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.
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