Dataset Information

Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all-cause mortality: Findings from the SMART cohort.

ABSTRACT:

Aim

To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all-cause mortality caused by type 2 diabetes (T2D).

Methods

Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL-cholesterol, triglycerides and micro-albuminuria), and what proportion of the effect of T2D on cardiovascular events and all-cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2D patients.

Results

Only 35% (95% CI 15-71%) of the excess cardiovascular risk caused by T2D is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance [proportion of mediated effect (PME) 18%, 95% CI 3-37%], followed by elevated triglycerides (PME 8%, 95% CI 4-14%) and micro-albuminuria (PME 7%, 95% CI 3-17%). Only 42% (95% CI 18-73%) of the excess mortality risk was mediated by the classical risk factors considered. The largest mediated effect was by micro-albuminuria (PME 18%, 95% CI 10-29%) followed by insulin resistance (PME 15%, 95% CI 1-33%).

Conclusion

A substantial amount of the increased cardiovascular risk and all-cause mortality caused by T2D cannot be explained by traditional vascular risk factors. Future research should focus on identifying non-classical pathways that might further explain the increased cardiovascular and mortality risk caused by T2D.

SUBMITTER: Sharif S

PROVIDER: S-EPMC6767388 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all-cause mortality: Findings from the SMART cohort.

Sharif Shahnam S Groenwold Rolf H H RHH van der Graaf Yolanda Y Berkelmans Gijs F N GFN Cramer Maarten J MJ Visseren Frank L J FLJ Westerink Jan J

Diabetes, obesity & metabolism 20190523 8

<h4>Aim</h4>To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all-cause mortality caused by type 2 diabetes (T2D).<h4>Methods</h4>Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL-cholesterol, triglycerides and micro-albuminuria), and what proportion of the effect of T2D ...[more]

PMID: 31062479

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Project description:BackgroundDespite the progressive aging of the population in industrialized countries, few studies have focused on the natural history of cardiovascular disease in the very old, and recommendations on prevention of cardiovascular disease in this population are lacking. We aimed to analyze all-cause mortality and cardiovascular events according to prevalent type 2 diabetes mellitus and established cardiovascular disease in nonagenarians from a Mediterranean population.MethodsWe analyzed the primary health records of all nonagenarians living in the Community of Madrid (N = 59,423) and collected data for 4 groups: Group 1, individuals without T2DM or established CVD (T2DM-, CVD-); Group 2, individuals without T2DM but with established CVD (T2DM-, CVD +); Group 3, individuals with T2DM but without established CVD (T2DM + , CVD-); and Group 4, individuals with both T2DM and established CVD (T2DM + , CVD +), taking into account the influence of sex on the outcomes. Follow-up was 2.5 years. The primary outcomes were cumulative incidence and incidence density rates for all-cause mortality, non-fatal myocardial infarction, non-fatal stroke (the first composite primary outcome [CPO1]), combined with heart failure (CPO2). We evaluated the adjusted effect of each group on all-cause mortality (Cox regression).ResultsMean age was 93.3 ± 2.8 years (74.2% women). Hypertension, dyslipidemia, heart failure, albuminuria, and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were significantly more prevalent in G4 than in the other groups (all p values < 0.001). We observed significantly higher cumulative incidence rates for all-cause mortality, CPO1, and CPO2 in participants belonging to G4 (all p values ≤ 0.001). People in G2 presented higher rates of all-cause mortality, heart failure, CPO1, and CPO2 than people in G3 (all p values ≤ 0.001). In the fully adjusted model, G4 independently predicted all-cause mortality (HR = 1.48 [95% CI, 1.40 to 1.57] vs reference G1 [p < 0.01]). In addition, significant HRs were recorded for cardiovascular disease alone (G2) and type 2 diabetes mellitus alone (G3) (1.13 and 1.14, respectively; both p values < 0.01).ConclusionsIn Spanish nonagenarians, established cardiovascular disease and type 2 diabetes mellitus conferred a modest risk of all-cause mortality. However, the simultaneous presence of both conditions conferred the highest risk of all-cause mortality.

Project description:BACKGROUND:Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current hypothesis is that oxidative stress might also play an important role in cardiovascular disease. In this study, we aimed to establish the role of serum free thiols in the general population by investigating their relationship with the risk of cardiovascular (CV) events and all-cause mortality. METHODS:Participants (n?=?5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study from the general population were included. At baseline, serum levels of free thiols were quantified and adjusted to total protein levels. Protein-adjusted serum free thiol levels were studied for their associations with clinical and biochemical parameters, as well as with the risk of CV events and all-cause mortality. RESULTS:The mean protein-adjusted serum free thiol level was 5.05?±?1.02??mol/g of protein. Protein-adjusted serum free thiols significantly predicted the risk of CV events, even after adjustment for potential confounding factors (hazard ratio [HR] per doubling 0.68 [95% confidence interval [CI] 0.47-1.00], P?=?0.048). Similarly, protein-adjusted serum free thiols were significantly predictive of the risk of all-cause mortality (HR per doubling 0.66 [95% CI 0.44-1.00], P?=?0.050). Stratified analyses revealed lower HRs for subjects with a lower body mass index (BMI), without hypertension, and without diabetes. Conversely, HRs were lower in subjects with albuminuria. CONCLUSIONS:In this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality. Our results highlight the potential significance and clinical applicability of serum free thiols since they are amendable to therapeutic intervention.

Dataset Information

Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all-cause mortality: Findings from the SMART cohort.

Aim

Methods

Results

Conclusion

Publications

Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all-cause mortality: Findings from the SMART cohort.

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