Abstract Objective To evaluate associations of fish oil supplementation and plasma omega 3 polyunsaturated fatty acids (n-3 PUFAs) with risks of macrovascular and microvascular complications among ...people with type 2 diabetes and to further explore the potential mediating role of metabolism-related biomarkers. Research Design and Methods This study included 20 338 participants with type 2 diabetes from the UK Biobank. Diabetic complications were identified through hospital inpatient records. Results During 13.2 years of follow-up, 5396 people developed macrovascular complications, and 4868 people developed microvascular complications. After multivariable adjustment, hazard ratios (HRs) and 95% confidence intervals (CIs) for patients with fish oil were 0.90 (0.85, 0.97) for composite macrovascular complications, 0.91 (0.84, 0.98) for coronary heart disease (CHD), 0.72 (0.61, 0.83) for peripheral artery disease and 0.89 (0.83, 0.95) for composite microvascular complications, 0.87 (0.79, 0.95) for diabetic kidney disease, and 0.88 (0.80, 0.97) for diabetic retinopathy. In addition, higher n-3 PUFA levels, especially docosahexaenoic acid (DHA), were associated with lower risks of macrovascular and microvascular complications. Comparing extreme quartiles of plasma DHA, the HRs (95% CIs) were 0.68 (0.57, 0.81) for composite macrovascular complications, 0.63 (0.51, 0.77) for CHD, and 0.59 (0.38, 0.91) for diabetic neuropathy. Moreover, biomarkers including lipid profile and inflammatory markers collectively explained 54.4% and 63.1% of associations of plasma DHA with risks of composite macrovascular complications and CHD. Conclusion Habitual use of fish oil supplementation and higher plasma n-3 PUFA levels, especially DHA, were associated with lower risks of macrovascular and microvascular complications among individuals with type 2 diabetes, and the favorable associations were partially mediated through improving biomarkers of lipid profile and inflammation.
IntroductionLong-term exposure to human immunodeficiency virus (HIV) associated immune dysregulation and adverse metabolic effects of highly active antiretroviral therapy could increase the risk for ...developing atherosclerotic cardiovascular disease (CVD). Previous prospective studies have also identified HIV infection as an independent risk factor for the development of heart failure (HF), though results remain inconsistent. We conducted a systematic review and meta-analysis of prospective studies to assess the association between HIV infection and incident HF.HypothesisWe hypothesized that HIV infection would increase the risk of incident HF, though this association may be modified by other demographic or clinical characteristics.MethodsWe performed a literature search of PubMed, EMBASE and Web of Science through June 1, 2020 to identify prospective studies which examined the association between HIV infection and incident HF among adults (age≥18 years). Study-specific risk estimates were combined using a random-effects model to calculate the pooled relative risk (RR) and 95% confidence intervals (CI).ResultsEight records with a total of 8,949,448 participants with 101,335 incident cases of HF (1,941 among HIV+ individuals and 99,394 among HIV- individuals) were included for meta-analysis. In our overall analysis, HIV infection was positively associated with incident HF, RR (95% CI)1.80 (1.51-2.15), I=85.6% (Figure 1). This association was largely consistent among individuals without a history of CVD, RR (95% CI)1.89 (1.51-2.37). HIV infection status tended to be a stronger risk factor for HF among younger adults (age<50 years), women, and individuals with low CD4 (<200 cells/mm) count.ConclusionsOur meta-analysis provides additional support that HIV may be an independent risk factor for HF, with potentially important clinical and public health implications for primary prevention.
Abstract only Background: Individuals with non-alcoholic fatty liver disease (NAFLD) are at increased risk for developing cardiovascular disease (CVD), often attributed to adverse metabolic ...derangements such as insulin resistance and elevated triglycerides. Marine omega-3 (n-3) fatty acids may partially ameliorate these metabolic consequences. Whether supplementation with n-3 fatty acids can reduce the risk of CVD in NAFLD remains unknown. Aims: To investigate the association between a NAFLD phenotype and incident CVD as well as assess whether randomization to n-3 fatty acids can modify this risk. Methods: Among 16,824 participants from the Vitamin D and Omega-3 Trial (VITAL; NCT01169259; a 2x2 factorial randomized trial of 1 g/d of EPA+DHA or 2000 IU/d of vitamin D 3 ) who provided baseline blood samples, we measured liver function tests. NAFLD was defined as baseline alanine aminotransferase (ALT)>40 U/L and/or aspartate aminotransferase (AST)>35 U/L, per guidance from the American Association for the Study of Liver Diseases. Incident CVD was a composite of myocardial infarction (MI), stroke, and CVD death. Multivariable-adjusted Cox models (adjusted for demographics, cardiovascular risk factors, and treatment assignment) were used to estimate hazard ratios (aHRs) and 95% confidence intervals (CI) for NAFLD with incident CVD. Effect of randomization to n-3 fatty acids was assessed among individuals with and without NAFLD. Results: We identified 2,495 participants with NAFLD at baseline, who tended to be younger, male, and non-White compared to individuals without NAFLD. After a median follow-up of 5.3 years, 522 CVD events were ascertained, with 101 occurring among those with NAFLD. Compared to individuals without NAFLD, those with NAFLD were at higher risk of developing CVD, aHR (95%CI): 1.48 (1.19, 1.84), P =0.0004. This association was predominantly driven by a higher incidence of total stroke, 1.53 (1.08, 2.17), P =0.02, compared with MI, 1.15 (0.81, 1.64), P =0.43. Randomization to n-3 fatty acids did not significantly reduce CVD incidence among individuals with, 1.13 (0.77, 1.68) or without NAFLD, 1.02 (0.85,1.24), P interaction =0.70. Conclusion: In a large primary prevention trial of older individuals, NAFLD was associated with a higher risk of CVD, particularly stroke. Randomization to n-3 fatty acids did not significantly reduce CVD outcomes in this high-risk population.
To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D).
We included 14,543 individuals with ...T2D from the UK Biobank. We defined a weighted healthy lifestyle score using nonsmoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyles. We created a genetic risk score (GRS) using 19 single nucleotide polymorphisms previously found to be associated with PAD. We modeled the association between lifestyle score and PAD, overall and stratified by PAD genetic susceptibility.
After a median 13.5 years of follow-up, 628 incident cases of PAD were documented. A linear inverse association between the weighted lifestyle score and PAD was observed, with a hazard ratio (HR) (95% CI) of 0.27 (0.19, 0.38) for favorable compared with unfavorable lifestyle (Ptrend < 0.0001). An estimated 58.3% (45.0%, 69.1%) of PAD in this population could be potentially avoidable if all participants attained a favorable lifestyle. Moreover, the PAD GRS was associated with increased PAD risk (HR 95% CI per SD increment: 1.13 1.03, 1.23). A favorable lifestyle was able to partially mitigate the excess risk of PAD associated with higher GRS, albeit as a nonsignificant interaction. Several biomarkers in the lipid metabolism, hepatic/renal function, and systemic inflammation pathways collectively explained 13.3% (8.5%, 20.1%) of the association between weighted lifestyle score and PAD.
A favorable lifestyle was associated with lower risk of PAD among individuals with T2D, independent of genetic predisposition to PAD.
OBJECTIVES:Existing studies evaluating the accuracy of heparin-binding protein for the diagnosis of sepsis have been inconsistent. We conducted a systematic review and meta-analysis to assess the ...totality of current evidence regarding the utility of heparin-binding protein to diagnose sepsis in patients with presumed systemic infection.
DATA SOURCE:PubMed, Embase, the China National Knowledge infrastructure, and WangFang electronic database were searched from inception to December of 2019.
STUDY SELECTION:Two independent reviewers identified eligible studies. Cohort and case-control studies, which measured serum levels of heparin-binding protein among adult patients with suspected sepsis, were eligible for inclusion.
DATA EXTRACTION:Two reviewers independently extracted data elements from the selected studies. A bivariate random-effects meta-analysis model was used to synthesize the prognostic accuracy measures. Risk of bias of studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 tool.
DATA SYNTHESIS:We identified 26 studies with 3,868 patients in the meta-analysis. Heparin-binding protein had a pooled sensitivity of 0.85 (95% CI, 0.79–0.90) and a pooled specificity of 0.91 (95% CI, 0.82–0.96) for the diagnosis of sepsis. There was low heterogeneity between the studies (I = 12%), and no evidence of publication bias was detected. Heparin-binding protein had a higher sensitivity and specificity when compared with procalcitonin (0.75 95% CI, 0.62–0.85 and 0.85 95% CI, 0.73–0.92) as well as C-reactive protein (0.75 95% CI, 0.65–0.84 and 0.71 95% CI, 0.63–0.77). Serial measurements of heparin-binding protein also showed that heparin-binding protein levels rose significantly at least 24 hours before a diagnosis of sepsis.
CONCLUSIONS:The diagnostic ability of heparin-binding protein is favorable, demonstrating both high sensitivity and specificity in predicting progression to sepsis in critically ill patients. Future studies could assess the incremental value that heparin-binding protein may add to a multimodal sepsis identification and prognostication algorithm for critically ill patients.
Abstract only Introduction: Incidence of heart failure (HF) is increased among individuals living with human immunodeficiency virus (HIV). Whether HIV adversely affects hospitalization and mortality ...rates among patients with diagnosed HF has not been systematically evaluated. Hypothesis: We hypothesized that HIV infection would increase the risk of hospitalization and all-cause mortality rates in patients with HF, independent of established risk factors. Methods: We performed a systematic search of PubMed, EMBASE, Cochrane Library and Web of Science through March 7 th , 2021 for cohort studies conducted in adult patients (age≥18 years) with diagnosed HF and ascertainment of HIV infection at baseline. Outcomes assessed include all-cause mortality, HF-associated hospitalization, and all-cause hospitalization. All studies included multivariable adjustments for demographics, cardiovascular risk factors, and comorbidities. Pooled hazard ratio (HR) and 95% confidence intervals (CI) were calculated using a random-effects model. Results: We identified 7 studies consisting of 10,363 HF patients living with HIV and 48,933 HIV negative HF controls. HF patients with HIV had a higher risk of all-cause mortality compared to HIV-negative HF patients, HR (95% CI): 1.20 (1.14, 1.25), I 2 =0%. Similarly, HIV infection was associated with increased risks of both HF-associated hospitalization and all-cause hospitalization, with HR (95% CI) of 1.31 (1.03, 1.65) and 1.27 (1.12, 1.44), respectively; though significant heterogeneity was observed for both of these outcomes, I 2 =80% and 62%, respectively. Conclusions: HIV infection was independently associated with increased risk of all-cause mortality and both HF-associated and all-cause hospitalizations among individuals with HF. Our data may have important implications for HF management in this high-risk population.
The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the ...associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
To examine the association of Life's Essential 8 (LE8) with the risk of recurrent cardiovascular events among patients with CHD.
This prospective cohort study included 11,997 patients with CHD from ...the UK Biobank. The LE8 score was generated using five lifestyle factors (diet, body mass index, physical activity, smoking, and sleep) and three biological factors (blood lipids, blood glucose, and blood pressure). LE8 score ranged from 0 to 100 and was categorized into quartiles. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% CI (confidence interval).
During a median follow up of 12.5 years, we documented 3366 recurrent cardiovascular events, 1068 myocardial infarction, 1829 heart failure events, 703 strokes, and 934 cardiovascular deaths. The multivariable-adjusted HR (95% CI) for the highest versus the lowest quartile of LE8 score was 0.57 (0.50, 0.65) for recurrent cardiovascular events, 0.66 (0.52, 0.83) for myocardial infarction, 0.54 (0.45, 0.67) for heart failure, 0.50 (0.36, 0.68) for stroke, and 0.46 (0.37, 0.56) for cardiovascular death. Furthermore, the population attributable fraction of the lowest to the highest quartile of LE8 score were ranged from 16.2% to 32.5% for the various cardiovascular outcomes. In addition, biomarkers including renal function and inflammation collectively explained 47.6%–87.7% of the associations between the lifestyle factors and recurrent cardiovascular events.
Better cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD. Clinicians should prioritize educating patients with CHD on the importance of optimal cardiovascular health for secondary prevention. In addition, our findings indicated significant mediation effect of biomarkers involving of glycemic control, renal function, liver function, lipid profile, and systemic inflammation on the associations between overall lifestyle factors and recurrent cardiovascular events.
•Evidence regarding the application of LE8 among patients with CHD is scarce.•Better cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD.•Biomarkers including renal function and inflammation collectively explained 47.6%–87.7% of the associations between the lifestyle factors and recurrent cardiovascular events.•The use of LE8 to target modifiable health behaviors may aid in reducing the population burden of recurrent cardiovascular events.
AbstractObjectivesTo evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and ...examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes.DesignProspective cohort study.SettingNurses’ Health Study II, US.Participants4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009.Main outcome measureSelf-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index <25.0), high quality diet (top two fifthsof the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372).ResultsOver a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (Ptrend<0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (Ptrend<0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed.ConclusionsAmong women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.