scholarly journals Genetic Determinants of Serum Calcification Propensity and Cardiovascular Outcomes in the General Population

2022 ◽  
Vol 8 ◽  
Author(s):  
Amber de Haan ◽  
Fariba Ahmadizar ◽  
Peter J. van der Most ◽  
Chris H. L. Thio ◽  
Zoha Kamali ◽  
...  

Background:Serum calciprotein particle maturation time (T50), a measure of vascular calcification propensity, is associated with cardiovascular morbidity and mortality. We aimed to identify genetic loci associated with serum T50 and study their association with cardiovascular disease and mortality.Methods:We performed a genome-wide association study of serum T50 in 2,739 individuals of European descent participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, followed by a two-sample Mendelian randomization (MR) study to examine causal effects of T50 on cardiovascular outcomes. Finally, we examined associations between T50 loci and cardiovascular outcomes in 8,566 community-dwelling participants in the Rotterdam study.Results:We identified three independent genome-wide significant single nucleotide polymorphism (SNPs) in the AHSG gene encoding fetuin-A: rs4917 (p = 1.72 × 10−101), rs2077119 (p = 3.34 × 10−18), and rs9870756 (p = 3.10 × 10−8), together explaining 18.3% of variation in serum T50. MR did not demonstrate a causal effect of T50 on cardiovascular outcomes in the general population. Patient-level analyses revealed that the minor allele of rs9870756, which explained 9.1% of variation in T50, was associated with a primary composite endpoint of all-cause mortality or cardiovascular disease [odds ratio (95% CI) 1.14 (1.01–1.28)] and all-cause mortality alone [1.14 (1.00–1.31)]. The other variants were not associated with clinical outcomes. In patients with type 2 diabetes or chronic kidney disease, the association between rs9870756 and the primary composite endpoint was stronger [OR 1.40 (1.06–1.84), relative excess risk due to interaction 0.54 (0.01–1.08)].Conclusions:We identified three SNPs in the AHSG gene that explained 18.3% of variability in serum T50 levels. Only one SNP was associated with cardiovascular outcomes, particularly in individuals with type 2 diabetes or chronic kidney disease.

2009 ◽  
Vol 2 ◽  
pp. CMED.S3479 ◽  
Author(s):  
Jayne Palmer ◽  
Anupama Kalsekar ◽  
Kristina Boye ◽  
Gordon Goodall

Objectives There is an established causal link between obesity and cardiovascular outcomes. The aim of this review was to determine whether an independent relationship exists between anthropometric measurements of weight (typically body mass index [BMI]) and cardiovascular outcomes (e.g. angina, myocardial infarction, congestive heart failure, stroke, and mortality due to cardiovascular disease) in the general population and in patients with type 2 diabetes. Methods A review of the medical literature published between 1988 and May 2008 was conducted using the PubMed, EMBASE, Cochrane and Center for Review and Dissemination databases. Studies longer than 12 months, with ≥500 adult subjects and published in English were included. Results In studies conducted in general populations there was an overall trend towards increased risk for adverse cardiovascular outcomes with increasing BMI. The nature and strength of this relationship varied according to the measurement used (e.g. BMI, waist circumference, waist-to-hip ratio) and the population studied, with notable differences observed in Asian/Asia-Pacific compared with European or North American-based studies. However, data from diabetes-specific populations are limited. Conclusions In general, the degree of being overweight or obese was associated with an elevated risk of adverse cardiovascular events and mortality. Although inextricable links exist between obesity, type 2 diabetes and cardiovascular disease in the general population, the extent to which findings can be extrapolated to a diabetes-specific population is limited.


2021 ◽  
Vol 9 (1) ◽  
pp. e001413
Author(s):  
Jonathan Yap ◽  
Kamalesh Anbalakan ◽  
Wan Ting Tay ◽  
Daniel Ting ◽  
Carol Yim Cheung ◽  
...  

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methodsThis was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.ResultsA total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p<0.001) and MACE (adjusted HR 1.64, 95% CI 1.39 to 1.93, p<0.001). In those with diabetes, higher HbA1c levels were associated with increased MACE rates (adjusted HR (per 1% increase) 1.18, 95% CI 1.11 to 1.26, p<0.001) but not mortality (p=0.115). Subjects with two microvascular complications had significantly higher mortality and MACE compared with those with only either microvascular complication (adjusted p<0.05) and no microvascular complication (adjusted p<0.05).ConclusionDiabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
Toshinari Takamura ◽  
...  

Abstract Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Jimmy D Alele ◽  
Kelly J Hunt ◽  
Bruce W Hollis ◽  
Deirdre K Luttrell ◽  
Louis M Luttrell ◽  
...  

BACKGROUND: Few studies have examined the relationship between vitamin D levels and incident cardiovascular events in large well-characterized type 2 diabetes cohorts. METHODS: We performed prospective analyses to determine associations between vitamin D status and vascular endpoints among 936 Veterans Affairs Diabetes Trial (VADT) participants (mean age 59.7 years; 96.7% male; 40.4% minority). 25 (OH)-vitamin D was measured a median of two years after entry into the VADT study and participants were subsequently followed an average of 3.7 years for outcomes. Cox proportional hazard models were used to calculate hazard ratios (HRs) for macrovascular endpoints in relation to vitamin D quartile. The primary composite endpoint included documented myocardial infarction; stroke; death from cardiovascular causes; new or worsening congestive heart failure; surgical intervention for cardiac, cerebrovascular, or peripheral vascular disease; inoperable coronary artery disease; and amputation for ischemic gangrene. RESULTS: On average VADT participants had high cardiovascular risk at entry into the study: 65.3% of the patients recruited were obese, 38.5% had previously had a vascular event, 78.7% had hypertension and 59.5% were using statins. During follow-up, 17.2%, 5.0%, 5.9%, 2.4% and 6.6% of participants had a primary composite endpoint, myocardial infarction, chronic heart failure, cardiovascular death or all-cause death, respectively. After adjusting for age, minority status, treatment arm and history of prior event, individuals in the lowest quartile of vitamin D (i.e., 1 to 15.9 ng/ml) were at similar risk of the primary composite endpoint [HR=1.26 (95% CI: 0.81, 1.96)], myocardial infarction [HR=1.13 (95% CI: 0.53, 2.42)], congestive heart failure [HR=1.44 (95% CI: 0.67, 3.06)], cardiovascular death [HR=0.86 (95% CI: 0.28, 2.63)], and death from any cause [HR=1.04 (95% CI: 0.53, 2.04)] as individuals in the highest quartile of vitamin D (i.e., 29.9 to 77.2 ng/ml). CONCLUSIONS: These data indicate that vitamin D status had no significant impact on the incidence of macrovascular events in a cohort of high-risk veterans with type 2 diabetes mellitus in which traditional risk factors were managed according to current treatment guidelines. SUPPORT: This work was supported by American Heart Association Grant-in-Aid AHA0755466U and the Research Service of the Charleston SC VA Medical Center.


Diabetologia ◽  
2017 ◽  
Vol 60 (10) ◽  
pp. 1883-1891 ◽  
Author(s):  
Emilie H. Zobel ◽  
Bernt Johan von Scholten ◽  
Henrik Reinhard ◽  
Frederik Persson ◽  
Tine W. Hansen ◽  
...  

2020 ◽  
Author(s):  
Ga Eun Nam ◽  
Wonsock Kim ◽  
Kyungdo Han ◽  
Chung-woo Lee ◽  
Yeongkeun Kwon ◽  
...  

<b>Objective: </b>Obesity and type 2 diabetes are risk factors for cardiovascular diseases and mortality, and that commonly result in weight variabilities. We aimed to investigate the association between body weight variability and risk of major cardiovascular outcomes and mortality in individuals with type 2 diabetes using large-scale, nationwide cohort data on the Korean population. <div><p><b>Research Design and Methods: </b>We enrolled 624,237 individuals with type 2 diabetes who underwent health examinations provided by the Korean National Health Insurance System between 2009 and 2010, with ≥3 body weight measurements within 5 years since enrollment and followed up until the end of 2017. We assessed body weight variability using four indices, including variability independent of the mean (VIM). Multivariable-adjusted Cox proportional hazards regression analysis was performed.</p> <p><b>Results: </b>During the follow-up, 15,832, 25,038, and 44,716 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively, were recorded. Body weight variability was associated with increased risks of major cardiovascular outcomes after adjusting for confounding variables. Compared with the hazard ratios (HRs) of the lowest quartile group, the HRs (95% CIs) of the highest quartile group of VIM for body weight were 1.15 (1.10–1.20), 1.22 (1.18–1.26), and 1.58 (1.53–1.62) for MI, stroke, and all-cause mortality, respectively.</p> <p><b>Conclusions: </b>Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in type 2 diabetes patients and may be a predictor of cardiovascular outcomes in such patients. Appropriate interventions to maintain stable weight could positively influence health outcomes in type 2 diabetes patients.</p> </div> <br>


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