Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES

<a><b>Objective</b></a> Despite periodical monitoring of cobalamin (vitamin B12) in metformin-treated diabetic patients is recommended, the cobalamin-associated mortality benefits or risks remains unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in diabetic adults using metformin or not. <p><b>Methods</b> This study included 3,277 adults with type 2 diabetes from NHANES and followed up until December 31, 2015. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.</p> <p><b>Results </b>Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin, intakes from foods or cobalamin supplements regardless of metformin treatment (each p ≥0.120). The doubling of methylmalonic acid (MMA, a cobalamin-deficiency marker) was significantly associated with higher all-cause (HR 1.31 95%CI 1.18–1.45, p <0.001) and cardiac mortality (HR 1.38 95%CI 1.14–1.67, p =0.001). Cobalamin sensitivity was assessed by the combination of binary B12_low/high and MMA_low/high (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMA_highB12_high) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMA_lowB12_low, MMA_lowB12_high, MMA_highB12_low, and MMA_highB12_high groups were1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers.</p> <p><b>Conclusions</b> Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.</p>

Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES

<a><b>Objective</b></a> Despite periodical monitoring of cobalamin (vitamin B12) in metformin-treated diabetic patients is recommended, the cobalamin-associated mortality benefits or risks remains unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in diabetic adults using metformin or not. <p><b>Methods</b> This study included 3,277 adults with type 2 diabetes from NHANES and followed up until December 31, 2015. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.</p> <p><b>Results </b>Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin, intakes from foods or cobalamin supplements regardless of metformin treatment (each p ≥0.120). The doubling of methylmalonic acid (MMA, a cobalamin-deficiency marker) was significantly associated with higher all-cause (HR 1.31 95%CI 1.18–1.45, p <0.001) and cardiac mortality (HR 1.38 95%CI 1.14–1.67, p =0.001). Cobalamin sensitivity was assessed by the combination of binary B12_low/high and MMA_low/high (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMA_highB12_high) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMA_lowB12_low, MMA_lowB12_high, MMA_highB12_low, and MMA_highB12_high groups were1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers.</p> <p><b>Conclusions</b> Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.</p>

Bifurcation functional significance score as predictor of mortality: a validating study

Considerable progress has been made in the treatment of coronary bifurcation stenosis. Anatomical characteristics of the vessel and lesion, however, fail to give information about the functional significance of the bifurcation stenosis. To the best of our knowledge, there is no study that systematically establishes the baseline functional significance of coronary stenosis and its effect on procedural and clinical outcomes. Patients with significant angiographic bifurcation lesions defined as diameter stenosis > 50% in main vessel and/or side branch were included. FFR was performed in main vessel (MV) and side branch (SB) before and after percutaneous coronary intervention (PCI). 169 patients from Fiesta study (derivation cohort) and 555 patients from prospective bifurcation registry (clinical effect cohort) were analyzed to validate angiographic prediction score (BFSS) used to determine the potentially functional significance of coronary bifurcation stenosis. Bifurcation functional significance score (including the following parameters—SYNTAX ≥ 11, SB/MB BARI score, MV %DS ≥ 55%, main branch (MB) %DS ≥ 65%, lesion length ≥ 25 mm) with a maximum value of 11 was developed. A cut-off value of 6.0 was shown to give the best discriminatory ability—with accuracy 87% (sensitivity 77%, specificity 96%, p < 0.001). There was also a significant difference in all-cause mortality between patients with BFSS ≥ 6.0 vs. BFSS < 6.0–25.5% vs. 18.4%, log-rank p = 0.001 as well as cardiac mortality: BFSS ≥ 6.0 vs. BFSS < 6.0–17.7% vs. 14.5%, log-rank (p = 0.016). The cardiac mortality was significantly lower in patients with smaller absolute SB territory, p = 0.023. An angiographic score (BFSS) with good discriminatory ability to determine the functional significance of coronary bifurcation stenosis was developed. The value for BFSS ≥ 6.0 can be used as a discriminator to define groups with higher risk for all-cause and cardiac mortality. Also, we found that the smaller side branches pose greater mortality risk.

Socioeconomic Influence on Cardiac Mortality in the South Asian Region: New Perspectives from Grey Modeling and G-TOPSIS

Background. Measuring the potential socioeconomic factors of cardiac mortality is fundamental to identifying treatments, setting priorities, and effectively allocating resources to minimize disease burden. The study sought to present a methodology that explores the connections between urbanization, population growth, human development index (HDI), access to energy, unemployment, and cardiovascular disease (CVD) mortality within the South Asian Association for Regional Cooperation (SAARC) nations to mitigate the cardiac disease burden. Methods. This investigation uses multiple-criteria decision-making methodologies to analyze data between 2001 and 2017 commencing with a mathematical grey incidence analysis (GIA) methodology to estimate weights and rank nations based on CVD mortality. Then, utilizing the conservative min-max model approach, we sought to determine which country contributes the most to CVD mortality among all South Asian nations. The grey preference by similarity to ideal solution (G-TOPSIS) method is adopted for further optimization by prioritizing the selected factors that have the greatest influence on CVD mortality. Results. The estimated statistic highlights that, among SAARC nations, Pakistan has a significant proportion of the disease burden attributable to cardiac events. In addition, HDI showed a significant contribution in the reduction of CVD mortality, whereas unemployment showed a significant contribution in the rise of CVD mortality among all selected variables. Conclusions. This investigation may facilitate researchers with a multiple-criteria decision-making roadmap to help them enhance the quality of their studies and their understanding of how to use multiple-criteria decision-making techniques to evaluate and prioritize the influencing factors of disease mortality in healthcare research. Further, the study outcomes provide additional practical knowledge for appropriate policy solutions.

Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa)

Purpose Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. Methods A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. Results After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85–1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88–1.25). Conclusions Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

Very long-term benefits of cardiac rehabilitation on mortality and cardiovascular events after percutaneous coronary intervention

Background Short and medium-term benefits of cardiac rehabilitation (CR) after an acute myocardial infarction (AMI) have been well studied. However, studies on long-term benefits of such programs after percutaneous coronary intervention (PCI) are scarce. Purpose The aim of our study was to evaluate the impact of cardiac rehabilitation (CR) on very long-term mortality and morbidity after PCI. Methods We conducted a retrospective cohort study of 701 patients who underwent PCI at our hospital between 2004 and 2011. Patients were classified into two cohorts based on whether or not they participated in a CR program phase II. A follow-up was performed in May 2020. We collected the events occurring during a median follow-up of 11 years. Results 701 patients were included in our study: 291 (41.5%) participated in the CR program, whereas 410 (58.4%) refused to do it. AMI was the most frequent indication for PCI (51.9%), followed by unstable angina (42.8%). The characteristics of the cohort based on participation in the CR program are shown in the table below. Patients who participated in the CR program were younger and mostly male. However, those who refused to do it had a higher cardiovascular risk due to a higher percentage of multivessel disease, diabetes mellitus, kidney failure and history of cerebrovascular accident. Using multivariate logistic regression, CR participation was found to be associated with significantly reduced all-cause mortality (19.5 vs 48.4%; OR 0.455; IC95% 0.295–0.701; p&lt;0.001) and cardiac mortality (4.5% vs 18.0%; OR 0.361; IC95% 0.181–0.721; p 0.004). CR is also associated with a substantial decrease in heart failure hospitalization (10.0% vs 24.8%; OR 0.557; IC95% 0.331–0.937; p 0.027) and incidence of stroke (5.5% vs 10.6%; OR 0.491; IC95% 0.271–0.890; p&lt;0.017) during the follow-up. No significant differences were observed in re-AMI (20.6% vs 24.1%, p=NS). Conclusion CR participation after PCI is associated with lower all-cause mortality, cardiac mortality, heart failure hospitalization rates and morbidity during long-term follow-up. FUNDunding Acknowledgement Type of funding sources: None.

Different Impact of Beta-Blockers on Long-Term Mortality in Heart Failure Patients with and without Chronic Obstructive Pulmonary Disease

The administration of beta-blockers is challenging and their efficacy is unclear in heart failure (HF) patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association of beta-blockers with mortality in such patients. This multicenter observational cohort study included hospitalized HF patients with a left ventricular ejection fraction <50% and evaluated them retrospectively. COPD was diagnosed based on medical records and/or the clinical judgment of each investigator. The study endpoints were two-year all-cause, cardiac, and non-cardiac mortality. This study included 83 patients with COPD and 1760 patients without. Two-year all-cause, cardiac, and non-cardiac mortality were observed in 315 (17%), 149 (8%), and 166 (9%) patients, respectively. Beta-blockers were associated with lower all-cause mortality regardless of COPD (COPD: hazard ratio [HR] 0.39, 95% CI 0.16–0.98, p = 0.044; non-COPD: HR 0.62, 95% CI 0.46–0.83, p = 0.001). This association in HF patients with COPD persisted after multivariate analysis and inverse probability weighting and was due to lower non-cardiac mortality (HR 0.40, 95% CI 0.14–1.18. p = 0.098), not cardiac mortality (HR 0.37, 95% CI 0.07–2.01, p = 0.248). Beta-blockers were associated with lower all-cause mortality in HF patients with COPD due to lower non-cardiac mortality. This may reflect selection biases in beta-blocker prescription.

Effect of Sacubitril/Valsartan Combined with Dapagliflozin on Long-Term Cardiac Mortality in Heart Failure with Reduced Ejection Fraction

The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.