Elevated urine albumin-to-creatinine ratio increases the risk of new-onset heart failure in patients with type 2 diabetes.

BACKGROUND: Although albuminuria has been linked to heart failure in the general population, the relationship between urine albumin-to-creatinine ratio (uACR) and heart failure in type 2 diabetes patients is not well understood. We aimed to investigate the relationship between uACR and new-onset heart failure (HF) in type 2 diabetics. METHODS: We included 9287 Chinese participants with type 2 diabetes (T2D) but no heart failure (HF) who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3-30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). The relationship between uACR and new-onset HF was studied using Cox proportional hazard models and restricted cubic spline. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. RESULTS: 216 new-onset HF cases (2.33%) were recorded after a median follow-up of 4.05 years. When compared to normal uACR, elevated uACR was associated with a progressively increased risk of new-onset HF, ranging from microalbuminuria (adjusted HR, 2.21; 95% CI 1.59-3.06) to macroalbuminuria (adjusted HR, 6.02; 95% CI 4.11-8.80), and 1 standard deviation (SD) in ln (uACR) (adjusted HR, 1.89; 95% CI 1.68-2.13). The results were consistent across sex, estimated glomerular filtration rate, systolic blood pressure, and glycosylated hemoglobin subgroups. The addition of uACR to established HF risk models improved the HF risk prediction efficacy. CONCLUSIONS: Increasing uACR, even below the normal range, is an independent risk factor for new-onset HF in a type 2 diabetic population. Furthermore, uACR may improve HF risk prediction in community-based T2D patients.

[Impact of ideal health behaviors and factors on the newly developed carotid plaques].

OBJECTIVE: To explore the impact of ideal health behaviors on the newly developed carotid plaques. METHODS: A total of 5 852 employees (including retired employees from Tangshan Kailuan company) aged over 40 years were included in this study through stratified random sampling. Subjects with previous stroke, transient ischemic attack, myocardial infarction were excluded. Results from the unified questionnaire, blood biochemistry measurements and ultrasonography carotid artery measurements were analyzed. Present study analyzed the data from 2 372 participants without carotid plaques in 2010-2011 examinations. The newly developed carotid plaques in 2012-2013 health examinations were observed and multiple logistic regression analysis was used to explore the impact of ideal health behaviors and factors on the newly developed carotid plaques. RESULTS: (1) There were 359 subjects with newly developed carotid artery plaques among the 2 372 subjects (15.1%), prevalence rate was 23.1% (43/186), 17.5% (186/1 065), 12.4% (122/986), 5.9% (8/135) in the groups with 0-1, 2-3, 4-5 and 6-7 components of ideal cardiovascular health behaviors and factors, respectively (P < 0.001). (2) Multiple logistic regression analysis showed that after adjusting for age, gender, high density lipoprotein cholesterol, heart rate, and high sensitive c-reactive protein, compared to with 0-1 components of ideal cardiovascular health behaviors and factors, participants with 4-5 and 6-7 components of ideal cardiovascular health behaviors and factors were associated with reduced risk of the newly developed carotid plaques, the OR (95% CI) values were 0.52(0.34-0.80) and 0.28(0.12-0.64), respectively. CONCLUSION: Higher number of ideal cardiovascular health behaviors and factors is associated with lower incidence of newly developed carotid plaques.

Comparison of the correlation of creatinine- and cystatin C-Based estimated GFR and their differences with new-onset heart failure in a community-based population with type 2 diabetes.

AIMS: This study aimed to investigate the impact of different estimated glomerular filtration rate (eGFR) values like cystatin C-based eGFR (eGFRcys), creatinine-based eGFR (eGFRcr), and their difference (eGFRdiff; eGFRcys -eGFRcr), on the incidence of heart failure (HF) in patients with type 2 diabetes(T2D). METHODS: Being a prospective cohort study, it included 7,967 patients with T2D who underwent serum creatinine and cystatin C tests as part of the Kailuan Group's 6th annual health examination (2016). Subsequently, eGFRcys, eGFRcr, and eGFRdiff were calculated. Patients were categorized into three groups: negative (<-15 mL/min/1.73 m2), midrange (-15 to 15 mL/min/1.73 m2), and positive (> 15 mL/min/1.73 m2) eGFRdiff groups, respectively. Furthermore, the relationship between the various eGFR measurements and new-onset HF were studied using Cox proportional hazards regression, and the potential improvement in predictive capability was evaluated by adding these eGFR metrics to established HF risk models. RESULTS: Among 7967 participants with mean age of 60.51 years, there were 20.92% women and 79.08% men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73m2 in 41.3% of participants. During a median follow-up period of 3.76 years, there were 172 (2.16%) new HF cases and 517 (6.49%) all-cause deaths. The cumulative incidence of HF in the midrange, negative, and positive eGFRdiff groups was 1.74%, 4.10%, and 0.61%, respectively (p < 0.001). In multivariable adjusted models, participants in the negative eGFRdiff group had higher risk of HF compared with the midrange eGFRdiff group (HR, 2.15; 95% CI, 1.57-2.94). Conversely, participants in the positive eGFRdiff group had lower risk for HF (HR, 0.40; 95% CI, 0.17-0.93). And each 15 mL/min/ 1.73 m2 higher eGFRdiff was associated with 34% (HR, 0.66; 95% CI, 0.58 - 0.47)lower risk of incident HF. The predictive capacity for HF risk in diabetic individuals was enhanced by adding eGFRcys or eGFRdiff to established HF risk models, with eGFRcys showing more significant additional predictive value. CONCLUSION: These findings suggest that large differences between eGFRcys and eGFRcr were common in community-based population with T2D. Different eGFR metrics can independently predict HF incidence in patients with T2D. Additionally, metrics like eGFRcys and eGFRdiff provide significant predictive value for HF risks beyond traditional risk factors, with eGFRcys showing more pronounced benefits in such cases.

Downregulating miR-432-5p exacerbates adriamycin-induced cardiotoxicity via activating the RTN3 signaling pathway.

BACKGROUND: Adriamycin (ADR) is a widely used chemotherapy drug in clinical practice and it causes toxicity in the myocardium affecting its clinical use. miR-432-5p is a miRNA primarily expressed in myocardial cells and has a protective effect in the myocardium. We aim to explore the protective effect of miR-432-5p on ADR-caused impaired mitochondrial ATP metabolism and endoplasmic reticulum stress (ERs). METHOD: The primary cardiomyocytes were obtained from neonatal mice and the ADR was added to cells, meanwhile, a mice model was constructed through intravenous ADR challenge, and expression levels of miR-432-5p were examined. Subsequently, the miR-432-5p was introduced in vitro and in vivo to explore its effect on the activity of mitochondrial ATP synthesis, autophagy, and ER stress. The bioinformatics analysis was performed to explore the target of miR-432-5p. RESULTS: ADR decreased the expression of miR-432-5p in cardiomyocytes. It also decreases mitochondrial ATP production and activates the ER stress pathway by increasing the expression of LC3B, Beclin 1, cleaved caspase 3, and induces cardiac toxicity. miR-432-5p exogenous supplementation can reduce the cardiotoxicity caused by ADR, and its protective effect on cardiomyocytes depends on the down-regulation of the RTN3 signaling pathway in ER. CONCLUSION: ADR can induce the low expression of miR-432-5p, and activate the RTN3 pathway in ER, increase the expression of LC3B, Beclin 1, cleaved caspase 3, CHOP, and RTN3, and induce cardiac toxicity.

An elevated urinary albumin-to-creatinine ratio increases the risk of incident cardia-cerebrovascular disease in individuals with type 2 diabetes.

AIMS: We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D). METHODS: We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3-30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). Cox regression models and restricted cubic spline were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. RESULTS: During a median follow-up of 4.05 years, 560 participants developed first CVD event (6.24%). After adjustment for potential confounders, participants with microalbuminuria had higher risks of CVD compared with normal uACR, with HRs of 1.57(95% CI 1.04-2.37) for myocardial infarction, 1.24(95% CI 1.00-1.54) for ischemic stroke,1.62(95% CI 0.73-3.61) for hemorrhagic stroke, and 1.30(95% CI 1.07-1.57) for total CVD. The risks gradually attenuated with uACR increase, with HRs of 2.86(95% CI 1.63-5.00) for myocardial infarction, 2.46(95% CI 1.83-3.30) for ischemic stroke, 4.69(95% CI 1.72-12.78) for hemorrhagic stroke, and 2.42(95% CI 1.85-3.15) for total CVD in macroalbuminuria. The addition of uACR to established CVD risk models improved the CVD risk prediction efficacy. CONCLUSIONS: Increasing uACR, even below the normal range, is an independent risk factor for new-onset CVD in T2D population. Furthermore, uACR could improve the risk prediction for CVD among community based T2D patients.

[Impact of ideal health behaviors and health factors on the detection rate of the carotid plaques].

OBJECTIVE: To explore the impact of ideal health behaviors and health factors on the detection rate of the carotid plaques. METHODS: Subjects with previous stroke, TIA, myocardial infarction were excluded from the study. A total of 5852 employees (active and retired employers from Tangshan Kailuan company) aged 40 years and over were included through stratified random sampling. Information was obtained from the unified questionnaire, measurements of blood biochemistry and carotid artery ultrasonography. RESULTS: (1) The carotid artery plaque detection rates were 67.0%, 52.3%, 50.5%, 44.3%, 37.2%, 31.9%, 26.1% and 4.2% in the groups with 0, 1, 2, 3, 4, 5, 6 and 7 components of ideal cardiovascular health behaviors and health factors, respectively. (2) The carotid artery plaques total burden score [TBS: M (Q1, Q3)] were 7(7,7), 7(5,7), 7(5,7), 5(3,5), 5(3,5), 5(3,5), 3(3,3), 3(3,3) in the groups with 0, 1, 2, 3, 4, 5, 6 and 7 components of ideal cardiovascular health behaviors and health factors, respectively. (3) Multiple logistic regression analysis showed that 3, 4, 5 and greater than 5 components of ideal cardiovascular health behaviors and health factors were protective factors against carotid plaques compared to less than 2 components of ideal cardiovascular health behaviors and factors (all P < 0.05), the OR (95%CI) values were 0.78 (0.62 - 0.98), 0.53(0.62 - 0.98), 0.52 (0.39 - 0.71) and 0.40 (0.25 - 0.64), respectively. CONCLUSION: Increasing ideal cardiovascular health behaviors and factors are negatively linked with the detection rate and TBS of the carotid plaques.