Serum total bilirubin levels and coronary heart disease - Causal association or epiphenomenon?

Observational epidemiological evidence supports a linear inverse and independent association between serum total bilirubin levels and coronary heart disease (CHD) risk, but whether this association is causal remains to be ascertained. A Mendelian randomization approach was employed to test whether serum total bilirubin is causally linked to CHD. The genetic variant rs6742078 - well known to specifically modify levels of serum total bilirubin and accounting for up to 20% of the variance in circulating serum total bilirubin levels - was used as an instrumental variable. In pooled analysis of estimates reported from published genome-wide association studies, every copy of the T allele of rs6742078 was associated with 0.42 standard deviation (SD) higher levels of serum total bilirubin (95% confidence interval, 0.40 to 0.43). Based on combined data from the Coronary Artery Disease Genome wide Replication and Meta-analyses and the Coronary Artery Disease (C4D) Genetics Consortium involving a total of 36,763 CHD cases and 76,997 controls, the odds ratio for CHD per copy of the T allele was 1.01 (95% confidence interval, 0.99 to 1.04). The odds ratio of CHD for a 1 SD genetically elevated serum total bilirubin level was 1.03 (95% confidence interval, 0.98 to 1.09). The current findings casts doubt on a strong causal association of serum total bilirubin levels with CHD. The inverse associations demonstrated in observational studies may be driven by biases such as unmeasured confounding and/or reverse causation. However, further research in large-scale consortia is needed.</p

Is the obesity paradox in heart failure dependant on cardiorespiratory fitness?

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Circulating Serum Magnesium and the Risk of Venous Thromboembolism in Men:A Long-term Prospective Cohort Study

BACKGROUND AND OBJECTIVE: Serum magnesium, an essential trace element involved in processes that regulate cardiovascular function, has been linked to the risk of atherosclerotic cardiovascular disease. However, the potential association between serum magnesium and venous thromboembolism (VTE) has not been previously investigated. We aimed to assess the prospective association of serum magnesium with the risk of VTE. METHODS: Serum magnesium was measured using atomic absorption spectrometry in 2,361 men aged 42–61 years with no history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE. RESULTS: A total of 159 incident VTE events were recorded during a median follow-up of 27.1 years. The risk of VTE per 1 SD increase in serum magnesium in the age-adjusted analysis was (HR 1.30; 95% CI 0.46–3.69). The association remained consistent in analyses adjusted for systolic blood pressure, body mass index, total cholesterol, triglycerides, smoking status, a history of type 2 diabetes, a history of coronary heart disease, medication for dyslipidemia, alcohol consumption, physical activity, socioeconomic status, serum active calcium, high-sensitivity C-reactive protein, and a history of cancer (HR 1.38; 95% CI 0.48–3.96). Comparing the extreme tertiles of serum magnesium, the corresponding adjusted HRs were 1.17 (95% CI 0.81–1.70) and 1.17 (95% CI 0.81–1.70), respectively. CONCLUSION: In a middle-aged Caucasian male population, serum-circulating magnesium was not associated with a future risk of VTE. Further studies in women, other age groups, and other populations are required to generalize these findings

Aspirin for primary prevention of cardiovascular and all-cause mortality events in diabetes:Updated meta-analysis of randomized controlled trials

AIMS: To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta-analysis. METHODS: Randomized controlled trials of aspirin compared with placebo (or no treatment) in people with diabetes with no history of cardiovascular disease were identified from MEDLINE, EMBASE, Web of Science, the Cochrane Library and a manual search of bibliographies to November 2015. Study-specific relative risks with 95% CIs were aggregated using random effects models. RESULTS: A total of 10 randomized trials were included in the review. There was a significant reduction in risk of major adverse cardiovascular events: relative risk of 0.90 (95% CI 0.81-0.99) in groups taking aspirin compared with placebo or no treatment. Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk, medication compliance and sex (P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infarction, coronary heart disease, stroke, cardiovascular mortality or all-cause mortality. Aspirin significantly reduced the risk of myocardial infarction for a treatment duration of ≤ 5 years. There were differences in the effect of aspirin by dosage and treatment duration on overall stroke outcomes (P for interaction for all < 0.05). There was an increase in risk of major or gastrointestinal bleeding events, but estimates were imprecise and not significant. CONCLUSIONS: The emerging data do not clearly support guidelines that encourage the use of aspirin for the primary prevention of cardiovascular disease in adults with diabetes who are at increased cardiovascular disease risk