Exploring the association between regional fat distribution and atrial fibrillation risks: a comprehensive cohort study.

Background: The contribution of total fat mass and regional fat distribution to the risk of AF has rarely been studied. Methods: This prospective cohort study(N=494,063) evaluated the association of total fat mass measured by fat percentage (FP) and regional fat measured by arm fat percentage (AFP), trunk fat percentage (TFP), and leg fat percentage (LFP) with incident AF. A subgroup (N = 25,581) underwent MRI, which allowed us to further assess whether visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) of the trunk fat exert different effects on AF incidence. Results: Over, a median 12.9 ± 1.86 years of follow-up, 29,658 participants (cumulative rate: 6.0%) developed AF. Each 1-standard deviation (SD) increase in LFP was associated with a 16% lower risk of AF (HR: 0.84, 95% CI: 0.82, 0.85). The association between FP and AF was weaker than that between LFP and AF (HR: 0.90, 95% CI: 0.89, 0.92). AFP and TFP only had a marginal association with a lower incidence of AF. Both the VAT and ASAT showed a U-shaped relationship with incident AF. Conclusions: Fat mass, mainly leg fat mass, was associated with a lower risk of AF. ASAT did not exert protective effects.

Cumulative blood pressure predicts risk of stroke in individuals with type 2 diabetes.

AIMS: To determine whether cumulative blood pressure (BP) could predict stroke in individuals with type 2 diabetes (T2D). METHODS: BP levels at baseline and the initial three visits were obtained from individuals participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who had not experienced a stroke. Cumulative elevations in BP were assessed by adding the weighted mean BP values at various time intervals. The association of cumulative BP with stroke was evaluated by a multivariate-adjusted Cox proportional hazard model analysis. RESULTS: Overall, 8282 participants were included (62.10% males and 37.90% females; mean age, 62.73 years). With a median follow-up period of 6.36 years, 324 (3.91%) and 305 (3.68%) patients had any and nonfatal stroke events, respectively. Only baseline systolic BP (SBP) independently predicted any stroke after adjustment for potential confounders, whereas cumulative SBP and pulse pressure independently predicted elevated stroke events. A strong dose-response relationship between cumulative BP and stroke was identified, and conventional risk factors combined with cumulative SBP improved prediction efficiency. CONCLUSION: Cumulative SBP independently predicts stroke in individuals with T2D and provides an incremental predictive value for stroke compared with baseline BP assessments. TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT00000620).

Glycemic variability evaluated by HbA1c rather than fasting plasma glucose is associated with adverse cardiovascular events.

Background: Although studies have shown that glycemic variability is positively associated with an increased risk of cardiovascular disease, few studies have compared hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) variability with adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Methods: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional hazards models were used to explore the relationship between HbA1c or FPG variability and the incidence of major adverse cardiovascular events (MACEs). Results: In total, 9,547 patients with T2DM were enrolled in this study. During the median 4.6 ± 1.5 years follow-up period, 907 patients developed MACEs. The risk of MACEs increased in the HbA1c variability group in each higher quartile of HbA1c variability (P < 0.01). Compared with those in the first quartile of HbA1c variability, patients in the fourth quartile had a hazard ratio of 1.37 (Model 2, 95% confidence interval: 1.13-1.67) for MACEs. Higher FPG variability was not associated with a higher risk of MACEs in patients with T2DM (P for trend=0.28). A U-shaped relationship was observed between HbA1c and FPG variability, and MACEs. Glucose control therapy modified the relationship between HbA1c and MACEs; participants with higher HbA1c variability receiving intensive glucose control were more likely to develop MACEs (P for interaction <0.01). Conclusion: In adults with T2DM, the relationship between glycemic variability evaluated using HbA1c and FPG was U-shaped, and an increase in HbA1c variability rather than FPG variability was significantly associated with MACEs. The relationship between HbA1c variability and MACEs was affected by the glucose control strategy, and a higher HbA1c variability was more strongly associated with MACEs in patients receiving an intensive glucose control strategy.

Association between accelerometer-derived physical activity and incident cardiac arrest.

AIMS: Studies on objectively measured physical activity (PA) have investigated acute cardiovascular outcomes but not cardiac arrest (CA). Our study aimed to investigate the dose-response relationship between accelerometer-measured PA and CA by intensity of PA. METHODS AND RESULTS: This prospective cohort study included 98 893 UK Biobank participants whose PA data were measured using wrist-worn accelerometers. Total PA volume was measured using the average overall acceleration. Minutes per week of light PA (LPA), moderate PA (MPA), and vigorous PA (VPA) were recorded. The incident CA was identified using diagnostic codes linked to hospital encounters and death records. Cox proportional hazard models with restricted cubic splines were used to study the associations, including sex differences. During the follow-up period (median: 7.31 years; interquartile range: 6.78-7.82 years), 282 incident CAs (0.39 per 1000 person-years) occurred. Total PA was inversely related to CA risk. The CA risk decreased sharply until the time spent in MPA or VPA reached ∼360 min or 20 min per week, respectively, after which it was relatively flat. The LPA was not associated with CA risk. Subgroup analyses showed a more pronounced association between PA and a reduced risk of CA in women compared to men. CONCLUSION: Accelerometer-measured PA, particularly MPA and VPA, was associated with a lower CA risk. Furthermore, a stronger association was observed in women than men.

ALP-assisted chemical redox cycling signal amplification for ultrasensitive fluorescence detection of DNA methylation.

Affinity assays allow direct detection of DNA methylation events without requiring a special sequence. However, the signal amplification of these methods heavily depends on nanocatalysts and bioenzymes, making them suffer from low sensitivity. In this work, alkaline phosphatase (ALP)-assisted chemical redox cycling was employed to amplify the sensitivity of fluorescence affinity assays for DNA methylation detection using Ru@SiO2@MnO2 nanocomposites as fluorescent probes. In the ALP-assisted chemical redox cycling reaction system, ALP hydrolyzed 2-phosphate-L-ascorbic acid trisodium salt (AAP) to produce AA, which could reduce MnO2 nanosheets to form Mn2+, making the fluorescence recovery of Ru@SiO2 nanoparticles possible. Meanwhile, AA was oxidized to dehydroascorbic acid (DHA), which was re-reduced by tris(2-carboxyethyl) phosphine (TCEP) to trigger a redox cycling reaction. The constantly generated AA could etch large amounts of MnO2 nanosheets and greatly recover Ru@SiO2 fluorescence, amplifying the signal of the fluorescence assay. Employing the proposed ALP-assisted chemical redox cycling signal amplification strategy, a sensitive affinity assay for DNA methylation detection was achieved using ALP encapsulated liposomes that were linked with the 5mC antibody (Ab) to bind with methylated sites. A detection limit down to 2.9 fM was obtained for DNA methylation detection and a DNA methylation level as low as 0.1% could be distinguished, which was superior to conventional affinity assays. Moreover, the affinity assays could detect DNA methylation more specifically and directly, implying their great potential for the analysis of tumor-specific genes in liquid biopsy.

Depression is associated with heart failure in patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of heart failure (HF). Depression, a common comorbidity of T2DM, may further increase the risk of heart failure (HF). We investigated the association between depression and incident HF in patients with T2DM. Methods and results: Depressive symptoms were assessed in the ACCORD Health-Related Quality of Life study participants at baseline, 12, 36, and 48 months using the nine-item Patient Health Questionnaire (PHQ-9). The severity of depressive symptoms was categorized as none (0-4 points), mild (5-9 points), or moderate-severe (10-24 points). Cox regression with PHQ-9 as a time-dependent covariate was used to assess the association between depression and incident HF. During the median follow-up of 8.1 years, 104 participants developed HF (incidence: 7.1/1,000 person-years). Half of the participants with moderate-severe depression were relieved and a significant percentage of participants without depression or with mild depression worsened to mild or moderate-severe depression during the follow-up period, respectively. Each unit increase in the PHQ-9 score was associated with a 5% higher risk of HF (hazard ratio [HR]:1.05, 95% confidence interval [CI]: 1.01-1.10). Patients with depression ever (HR: 2.23, 95% CI: 1.25-3.98) or persistent depression (HR: 2.13, 95% CI: 1.05-4.44) had a higher risk of HF than those without depression ever. Conclusion: Depressive symptoms change greatly in T2DM patients, depressive symptoms are an independent risk factor for HF. These results reinforce the importance of continuous evaluation and management of mental health status in T2DM patients with high HF risk.

Intensive blood pressure control for patients aged over 60: A meta-analysis of the SPRINT, STEP, and ACCORD BP randomized controlled trials.

OBJECTIVES: To evaluate the effects of intensive treatment to lower blood pressure (BP) on the risk of cardiovascular disease (CVD) among patients aged over 60 years. STUDY DESIGN: We extracted individual-level data of participants aged over 60 years from the SPRINT study and ACCORD study first, and then conducted a meta-analysis of major adverse cardiovascular events (MACEs) and other adverse events (hypotension and syncope) and renal outcomes across the SPRINT, STEP, ACCORD BP trials, which included 18,806 participants over 60 years of age. Participants were randomized to receive standard BP treatment or intensive BP treatment. MAIN OUTCOME MEASURES: Hazard ratios (HRs) were used to calculate summary statistics. RESULTS: In this meta-analysis, intensive treatment did not decrease either the all-cause mortality rate (HR: 0.98; 95 % confidence interval [CI]: 0.76-1.26; p = 0.87) or the cardiovascular mortality rate (HR: 0.77; 95 % CI: 0.54-1.08; p = 0.13). The incidence of MACEs (HR: 0.83; 95 % CI: 0.74-0.94; p = 0.003) and stroke (HR: 0.70; 95 % CI: 0.56-0.88; p = 0.002) was reduced, however. Intensive treatment had no effect on acute coronary syndrome (HR: 0.87; 95 % CI: 0.69-1.10; p = 0.24) or heart failure (HR: 0.70; 95 % CI: 0.40-1.22; p = 0.21). Intensive treatment increased the risk of hypotension (HR: 1.46; 95 % CI: 1.12-1.91; p = 0.006) and syncope (HR: 1.43; 95 % CI: 1.06-1.93; p = 0.02). Intensive treatment did not increase the risk of impaired kidney function among patients with chronic kidney disease (HR: 0.98; 95 % CI: 0.41-2.34; p = 0.96) or without chronic kidney disease (HR: 1.77; 95 % CI: 0.48-6.56; p = 0.40) at baseline. CONCLUSIONS: Intensive BP goals reduced the incidence of MACEs and increased the risk of other adverse events without significant changes in mortality or renal outcome.

Predicted lean body mass, fat mass, and heart failure in patients with type 2 diabetes mellitus.

BACKGROUND: High body mass index (BMI) is associated with a higher risk of heart failure (HF) in patients with new-onset type 2 diabetes mellitus (T2DM). However, limited studies have investigated the independent association between fat mass or lean body mass and HF risk among T2DM patients with cardiovascular disease (CVD) or high CVD risk. OBJECTIVES: To investigate the association between fat mass index (FMI, kg/m2) or lean BMI (LBMI, kg/m2) and HF risk. METHODS: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional-hazards models were applied to evaluate the association of FMI, LBMI, and BMI with HF risk. Discordant analysis was performed to compare the magnitude of this associations. RESULTS: HF occurred in 356 participants (3.7%). After adjusting for confounding factors, higher FMI values were independently associated with HF risk (HR: 1.72, 95% CI: 1.15-2.57, each 1 SD increase in FMI); LBMI was a protective risk factor for HF (HR: 0.58, 95% CI: 0.38-0.87,). After further adjusting for FMI, the association between BMI and HF risk (HR, 0.97; 95% CI, 0.67-1.42) disappeared. Compared with concordant values below the medians, discordant FMI above the median with BMI below yielded an HR of 1.78 (95% CI: 1.14-2.78) for HF. In contrast, BMI above the median with FMI below was not associated with HF risk (HR: 1.09, 95% CI: 0.57-2.09). CONCLUSIONS: The risk of HF conferred by higher BMI was primarily driven by the association between FMI and HF. After adjusting for BMI, LBMI played a protective role.

Relationship Between Regional Adiposity Distribution and Incident Heart Failure in General Populations without Cardiovascular Disease.

BACKGROUND: Obesity is associated with a high risk of heart failure. However, the contribution of regional fat distribution evaluated using bioimpedance analysis toward heart failure risk in the general population without cardiovascular disease has rarely been studied. METHODS: This study included 483,316 participants without heart failure and cardiovascular disease from the UK Biobank study. The regional fat mass was determined by bioimpedance analysis and calculated by dividing the square of height in meters (kg/m2). This study evaluated the association of regional fat mass (arm fat index [AFI], trunk fat index [TFI], and leg fat index [LFI]) with the risk of incident heart failure and whether regional fat mass adds a further prognostic value for heart failure besides body mass index (BMI) in a large prospective cohort study. RESULTS: During the median 12.1 years, 3134 incident heart failure cases occurred. After adjustment for BMI and other confounding factors, each 1-standard deviation increase in LFI was associated with a 21% lower heart failure risk even after adjusting for BMI and other confounding factors (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.73-0.85). However, we did not observe heart failure-associated risks with AFI and TFI (HR 1.04; 95% CI, 0.99-1.09; HR 0.97, 95% CI, 0.91-1.04, respectively). Subgroup analysis demonstrated that the protective role of LFI was more prominent in the elderly and female participants (P < .01). CONCLUSION: Regional fat measurement other than BMI can improve heart failure risk stratification; leg fat plays a protective role, yet arm and trunk fat do not, in the general population without cardiovascular disease.

Device-measured physical activity and type 2 diabetes mellitus risk.

Objectives: We investigated how device-measured physical activity (PA) volume (PA energy expenditure [PAEE]) and intensity (fraction of PAEE from moderate-to-vigorous PA [FMVPAEE]) were associated with the incidence of type 2 diabetes mellites (T2DM). Methods: This population-based prospective cohort study included 90,044 participants. The primary exposures were PAEE and FMVPAEE. The secondary exposures were energy expenditure exerted during light, moderate, and vigorous PA and their fraction of PAEE. Results: Each 1-SD increase in PAEE was associated with a 17% lower risk of T2DM (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.78-0.98). Each 1-SD increase in FMVPAEE was associated with a 21% lower incidence of T2DM (HR: 0.79, 95% CI: 0.74-0.83). Achieving the same PA volume (KJ/kg/day) through vigorous PA (HR: 0.88, 95% CI: 0.85-0.91) was more effective in preventing T2DM than moderate PA (HR: 0.97, 95% CI: 0.96-0.98) and light PA (HR: 0.99, 95% CI: 0.98-1.00). Conclusion: A higher PA volume is associated with a lower incidence of T2DM. Achieving the same PA volumes through higher-intensity PA is more effective than low-intensity PA in reducing T2DM incidence.

Changes in body mass index and waist circumference and heart failure in type 2 diabetes mellitus.

Background: To determine the association of unintentional changes in body mass index (BMI) and waist circumference (WC) with the risk of heart failure (HF) among adults with type 2 diabetes mellitus (T2DM). Methods: This was a randomized controlled trial (the Action to Control Cardiovascular Risk in Diabetes [ACCORD] study), with a double 2×2 factorial design conducted at 77 clinical centers across the United States and Canada. In total, the study comprised 10,251 patients with T2DM and cardiovascular disease (CVD) or at a high risk of CVD. The outcome of interest in the present analysis was incident HF, defined as the first hospitalization event for HF or death due to HF. Hospitalization for HF was based on documented clinical and radiological evidence. Death due to HF was based on clinical, radiological, or postmortem evidence of HF, with an absence of an acute ischemic event according to clinical or postmortem evidence. Results: Participants with class III obesity had the smallest BMI and WC changes, followed by those with normal weight, overweight, class I obesity, and class II obesity. Increasing BMI (hazard ratio [HR] per standard deviation increase, 1.24; 95% confidence interval [CI], 1.07-1.45) and WC (1.27; 1.10-1.47) were significantly associated with a higher risk of HF. The relationship between BMI and WC changes and HF formed a J-shaped curve, while stable BMI and WC were associated with lower risks of HF. Compared with participants in the first tertiles of BMI and WC change, those in the third tertiles had HRs of 1.41 (95% CI, 1.07-1.45) and 1.48 (1.12-1.95), respectively. Conclusion: In conclusion, our findings suggest a noteworthy association between BMI and WC changes among adults with T2DM in HF. We observed a distinctive J-shaped curve in this relationship, indicating that participants with both low and high BMI and WC changes were more susceptible to developing HF. Trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.

Obesity is associated with greater cognitive function in patients with type 2 diabetes mellitus.

Background: The impact of obesity on cognitive function in patients with type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to evaluate whether obesity, assessed by body mass index (BMI) was associated with cognitive function among T2DM patients and whether the effect of obesity on cognitive function was through brain structure. Methods: This was a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study. The cognitive test battery included the Digit Symbol Substitution Test (DSST), Mini-Mental State Exam (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and STROOP test, which were administered at baseline, and at 20, 40, and 80 months. A subgroup (n = 614) of the ACCORD-MIND study underwent MRI scanning at baseline and at 40 and 80 months. The total brain volume (TBV), abnormal white matter volume (AWM), abnormal gray matter volume (AGM), and abnormal basal ganglia volume (ABG) were estimated. The outcomes of this study were cognitive function and brain structure. Results: In the adjusted analyses, BMI was positively associated with the MMSE (ß:0.08, 95%CI,0.01-0.16, per standard deviation [SD] increase) and RAVLT scores (ß:0.09, 95%CI,0.01-0.18). It was also associated with a greater TBV (ß:7.48, 95%CI,0.29-14.67). BMI was not associated with the DSST or STROOP scores, and AWM, AGM, ABG. Mediation analysis found that the effect of BMI on MMSE/RAVLT was mediated through TBV. Conclusion: Obesity may be associated with greater cognitive function and the effect of BMI on cognitive function may be mediated by TBV among patients with T2DM. Clinical Trial Registration: http://www.clinicaltrials.gov, identifier NCT00000620.

Association of the cumulative triglyceride-glucose index with major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM. METHODS: This post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients' (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed. RESULTS: Over a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17-2.16), 1.97 (95% CI 1.19-3.26), and 1.66 (95% CI 1.02-2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value. CONCLUSIONS: In patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs. Trial registration URL: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.

Association of long-term visit-to-visit variability of HbA1c and fasting glycemia with hypoglycemia in type 2 diabetes mellitus.

Background: Self-management of blood glucose levels to avoid hypoglycemia is vital for patients with type 2 diabetes mellitus (T2DM). The association between specific metrics of glycemic variability (glycosylated hemoglobin A1c [HbA1c] and fasting plasma glucose [FPG]) and severe hypoglycemia has not been fully studied in patients with T2DM. Methods: In this post hoc analysis, patients with established T2DM with a high risk of cardiovascular disease were included in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The Cox proportional hazards model was used to investigate the relationship between glycemic variability and hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any third-party assistance (HAA). The prognostic value of HbA1c/FPG variability for our predefined outcomes was compared using Harrell's C method. Results: After adjusting for confounders, each increase in HbA1c variability of 1 standard deviation (SD) indicated a higher risk of HAA (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.03-1.16; P < 0.01) and HMA events (HR: 1.11; 95% CI: 1.03-1.20; P < 0.01). Meanwhile, each increase in FPG variability of 1 SD increased the risk of HAA (HR: 1.40; 95% CI: 1.31-1.49; P < 0.01) and HMA events (HR: 1.46; 95% CI: 1.35-1.57; P < 0.01). Meanwhile, models, including FPG variability, had better prognostic value for our predefined outcomes than HbA1c variability (P < 0.01). Conclusions: Increased visit-to-visit variability in HbA1c and fasting glycemia is associated with a greater risk of severe hypoglycemic events in T2DM patients. FPG variability is a more sensitive indicator than HbA1c variability. Trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.

Obesity Increases In-Hospital Mortality of Acute Type A Aortic Dissection Patients Undergoing Open Surgical Repair: A Retrospective Study in the Chinese Population.

Objective: The prevalence of obesity is increasing worldwide, and the role of the obesity paradox in cardiovascular surgery remains controversial. In this study, we redefined obesity according to the Chinese criteria and examined the relationship between obesity and in-hospital mortality in patients with acute type A aortic dissection (AAD) undergoing open surgical repair. Materials and Methods: A total of 289 patients with AAD (between 2014 and 2016) were divided into the non-obese group and obese group for correlation analysis, general information, demographic factors, blood biochemistry, surgical details, and complications, which were used as covariates. Survival was estimated by the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank test. Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression were used to evaluate the effect and interaction of obesity on surgical mortality. Results: All the 289 patients had a mean age of 48.64 (IQR 44.00-55.00) and 74.39% were men. Of the 289 patients, 228 were non-obese (78.89%) and 61 were obese (21.11%). Patients with obesity were younger and more prone to unstable blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)], preoperative hypoxemia and delirium, prolonged operative time, and surgical wound deep infection (p < 0.05). In the fully adjusted model, we observed an increased risk of in-hospital mortality in patients with obesity after fine-tuning other covariates including age and sex (HR = 2.65; 95% CI = 1.03 to 6.80; p = 0.042). The interaction suggested that obesity was more likely to cause death in elderly patients (age ≥ 60), although it was more common in younger patients (test for interaction, p = 0.012). Conclusion: Obesity, interacting with age, increases the risk of in-hospital mortality in patients with AAD undergoing open surgical repair. Although more verification is needed, we believe these findings provide further evidence for the treatment of AAD.

Remnant Cholesterol and Its Visit-to-Visit Variability Predict Cardiovascular Outcomes in Patients With Type 2 Diabetes: Findings From the ACCORD Cohort.

OBJECTIVE: Remnant cholesterol (remnant-C) predicts atherosclerotic cardiovascular disease, regardless of LDL-cholesterol (LDL-C) levels. This study assessed the associations between remnant-C and cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: This post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial used patient (type 2 diabetes >3 months) remnant-C and major adverse cardiovascular event (MACE) data from the study database. The associations between remnant-C and MACEs were evaluated using Cox proportional hazards regression analyses. We examined the relative MACE risk in remnant-C versus LDL-C discordant/concordant groups using clinically relevant LDL-C targets by discordance analyses. RESULTS: The baseline analysis included 10,196 participants, with further visit-to-visit variability analysis including 9,650 participants. During follow-up (median, 8.8 years), 1,815 patients (17.8%) developed MACEs. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in remnant-C was associated with a 7% higher MACE risk (hazard ratio [HR] 1.07, 95% CI 1.02-1.12, P = 0.004). In the fully adjusted model, the visit-to-visit remnant-C variability calculated using logSD (HR 1.41, 95% CI 1.18-1.69, P < 0.001) and logARV (HR 1.45, 95% CI 1.22-1.73, P < 0.001) was associated with MACEs. Residual lipid risk (remnant-C ≥31 mg/dL) recognized individuals at a higher MACE risk, regardless of LDL-C concentrations. Within each LDL-C subgroup (>100 or ≤100 mg/dL), high baseline remnant-C was associated with a higher MACE risk (HR 1.37, 95% CI 1.09-1.73, P = 0.007; HR 1.22, 95% CI 1.04-1.41, P = 0.015, respectively). CONCLUSIONS: Remnant-C levels were associated with MACEs in patients with type 2 diabetes independent of LDL-C, and visit-to-visit remnant-C variability helped identify those with higher cardiovascular risk.

Living Alone Is Not Associated With Cardiovascular Events and Hypoglycemia in Patients With Type 2 Diabetes Mellitus.

Objective: Living alone is often associated with reduced social support. However, there are limited data on the relationship between living alone and cardiovascular events or hypoglycemia in patients with type 2 diabetes mellitus (T2DM). This study reports a post-hoc analysis of the "Action to Control Cardiovascular Risk in Diabetes (ACCORD)" study. Research Design and Methods: The Cox proportional hazard models were used to compare the hazard ratios (HRs) for the adverse health events selected as primary endpoints in the study participants; these were compared between those living alone and those living with others. The primary outcomes were hypoglycemia requiring any assistance (HAA), hypoglycemia requiring medical assistance (HMA), and major cardiovascular events (MACEs, including cardiac death, non-fatal myocardial infarction (MI), and non-fatal stroke). Our study included 10,249 participants (2,078 living alone) with a follow-up period of 4.91 ± 1.22 years. Results: After a multivariable adjustment, the risk of HAA, HMA, and MACEs did not differ significantly between participants living alone and those living with others (HAA, HR: 0.88, 95% CI: 0.75-1.04, P = 0.13; HMA, HR: 1.11, 95% CI: 0.92-1.34, P = 0.26; MACEs, HR: 0.98, 95% CI: 0.80-1.19, P = 0.82). Participants living alone had higher levels of glycated hemoglobin in the middle follow-up period than those living with others. Conclusions: In patients with T2DM, living alone did not increase the risk of cardiovascular events (cardiac death, non-fatal MI, or non-fatal stroke) and hypoglycemia. Patients living alone had higher Hb1AC levels than those living with others. Clinicians should consider an effective blood glucose control regardless of their living arrangement.

Impact of Baseline and Trajectory of Triglyceride-Glucose Index on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus.

Background and Aims: This study aimed to evaluate the association of the triglyceride-glucose (TyG) index with the cardiovascular incidence in patients with type 2 diabetes mellitus (T2DM). Methods and Results: Secondary analysis in patients with long-lasting T2DM from the Action to Control Cardiovascular Risk in Diabetes study was performed. The primary outcome was the first occurrence of major adverse cardiovascular events (MACEs). The association between the baseline and trajectories of the TyG index and MACEs was evaluated by Cox proportional hazards regression analysis. During a median follow-up period of 8.8 years, 1,815 (17.8%) patients developed MACEs. After traditional cardiovascular risk factor adjustments, each 1-standard deviation increase in the TyG index was associated with a 19.00% higher MACE risk, similar to that in the TyG index quartile characterization. Four distinct trajectories of TyG indexes were identified: low (16.17%), moderate (40.01%), high (34.60%), and very high (9.30%). In multivariate analysis, high and very high TyG index trajectories showed a greater risk of future MACE incidence than the low TyG index trajectory. A similar association was observed between the TyG index and the occurrence of coronary heart disease. Conclusions: The baseline and trajectories of the TyG index were significantly associated with the occurrence of MACEs in patients with T2DM. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.

Changes in fat mass and lean body mass and outcomes in type 2 diabetes mellitus.

Previous studies have found that fat mass and lean body mass may act differently on the prognosis in patients type 2 diabetes mellitus (T2DM). However, the change of fat mass and lean body mass on prognosis in T2DM patients has not yet been investigated. We performed a Post hoc analysis of data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional hazards models were used to study the relationship between tertiles of the change trend in lean body mass index (LBMI, kg/m2/year) or fat mass index (FMI, kg/m2/year) and major cardiovascular adverse events (MACEs) and all cause mortality. Nine thousand, one hundred seventy-six T2DM patients with a mean follow-up of 9.52 ± 1.89 years were included in our study. The mean change in FMI per year was 0.10 ± 0.48 kg/m2. The mean change in LBMI per year was 0.05 ± 0.38 kg/m2. Normal weight patients had highest FMI/LBMI change; severely obese patients had lowest FMI/LBMI change. A U-shaped relationship was found between the change in FMI/LBMI and all cause mortality. A flat U-shaped relationship was also noted between the change in FMI or LBMI and MACEs. Compared with the second tertile, the first and third tertiles of the change in FMI (HR: 1.18, 95% CI 1.03-1.36; HR: 1.34, 95% CI 1.16-1.54, respectively)/LBMI (HR: 1.24, 95% CI 1.08-1.43; HR: 1.30, 95% CI 1.12-1.50, respectively) had higher all cause mortality; the third tertile of the change in FMI/LBMI showed a marginal increase of MACEs (HR: 1.15, 95% CI 1.01-1.32; HR: 1.17, 95% CI 1.02-1.33, respectively); sensitivity analysis and subgroup analysis showed these associations were not robust. Both lower and larger change in FMI or LBMI are associated with increased all cause mortality compared with the median change among patients with T2DM. Further study is needed to determine whether increased FMI or LBMI increases the risk of MACEs.Trial registration: clinicaltrials.gov., No. NCT00000620.

Significantly Increased Risk of All-Cause Mortality Among Type 2 Diabetes Patients Living Alone.

BACKGROUND: There is a lack of studies evaluating the association between living status and subsequent outcomes in patients with type 2 diabetes (T2DM). OBJECTIVES: This study aimed to assess the association between living alone and the risk of all-cause mortality in T2DM patients. METHODS: We performed a secondary analysis in patients with long-lasting T2DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The primary outcome was all-cause mortality. Multivariable Cox proportional hazard models was used to analyze and compare the hazard ratios (HRs) in patients living alone and with one or more adults. RESULTS: This study included 10,249 patients with T2DM. Of these, 2,078 (20.28%) were living alone and 8,171 (79.72%) lived with one or more adults. Over a median total follow-up of 8.8 years, 1,958 patients developed the primary endpoint. The all-cause mortality rates in patients living alone or living with one or more adults were 23.24 and 18.05%, respectively. Cox proportional hazard analysis showed that T2DM patients living alone had significantly higher rate of all-cause mortality than those living with others (HR, 1.34; 95% confidence interval [CI], 1.20-1.48; p < 0.001). After multivariable adjustment, living alone was an independent risk factor for all-cause mortality in patients with T2DM (adjusted HR, 1.27; 95% CI, 1.14-1.41; p < 0.001). Furthermore, the risks of both congestive heart failure (CHF) and fatal coronary heart disease (CHD) among 4,050 propensity score-matched patients were higher for patients living alone (respectively HR, 1.37; 95% CI, 1.08-1.74; p = 0.010; and HR, 1.16; 95% CI, 1.00-1.34; p = 0.047). CONCLUSIONS: The risk of all-cause mortality was significantly higher in T2DM patients living alone than in those living with one or more adults.