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Abstract Objective Population-based national data on the trends in expenditures related to coexisting atherosclerotic cardiovascular diseases (ASCVD) and diabetes is scarce. We assessed the trends in direct health care expenditures for ASCVD among individuals with and without diabetes, which can help to better define the burden of the co-occurrence of diabetes and ASCVD. Methods We used 12-year data (2008–2019) from the US national Medical Expenditure Panel Survey including 28,144 U.S individuals aged ≥ 18 years. Using a two-part model (adjusting for demographics, comorbidities and time), we estimated mean and adjusted incremental medical expenditures by diabetes status among individuals with ASCVD. The costs were direct total health care expenditures (out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources) from various sources (office-based visits, hospital outpatient, emergency room, inpatient hospital, pharmacy, home health care, and other medical expenditures). Results The total direct expenditures for individuals with ASCVD increased continuously by 30% from $14,713 (95% confidence interval (CI): $13,808–$15,619) in 2008–2009 to $19,145 (95% CI: $17,988–$20,301) in 2008–2019. Individuals with diabetes had a 1.5-fold higher mean expenditure that those without diabetes. A key driver of the observed increase in direct costs was prescription drug costs, which increased by 37% among all individuals with ASCVD. The increase in prescription drug costs was more pronounced among individuals with ASCVD and diabetes, in whom a 45% increase in costs was observed, from $5184 (95% CI: $4721–$5646) in 2008–2009 to $7501 (95% CI: $6678–$8325) in 2018–2019. Individuals with ASCVD and diabetes had $5563 (95% CI: $4643–$6483) higher direct incremental expenditures compared with those without diabetes, after adjusting for demographics and comorbidities. Among US adults with ASCVD, the estimated adjusted total direct excess medical expenditures were $42 billion per year among those with diabetes vs. those without diabetes. Conclusions In the setting of ASCVD, diabetes is associated with significantly increased health care costs, an increase that was driven by marked increase in medication costs.

Background It is unclear how metabolic syndrome (MetS) and diabetes affect Gal‐3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal‐3, and their joint associations with incident HF. Methods and Results We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996–1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross‐sectional associations of metabolic risk categories with high Gal‐3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal‐3 quartiles with HF. In cross‐sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10–1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32–1.92]) were associated with elevated Gal‐3. Over a median follow‐up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal‐3 in the lowest quartile, the combination of MetS with diabetes and Gal‐3 ≥75th percentile was associated with a 4‐fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30–5.73]). Gal‐3 provided HF prognostic information above and beyond MetS, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity cardiac troponin T, and CRP (C‐reactive protein) (ΔC statistic for models with versus without Gal‐3: 0.003; P=0.004). Conclusions MetS and diabetes are associated with elevated Gal‐3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal‐3.

Background The relation between age at diagnosis of type 2 diabetes (T2D) and hospitalization for heart failure (HHF) is unclear. We assessed the association between age at diagnosis of T2D and HHF. Methods and Results We conducted a population‐based cohort study using administrative health databases from the Canadian province of Ontario, including participants without prior heart failure. We identified people with new‐onset T2D between April 1, 2005 and March 31, 2015, and matched each person with 3 diabetes‐free adults, according to birth year and sex. We estimated adjusted hazard ratios (HRs) and rate ratios (RRs) for the association between age at T2D diagnosis and incident HHF, which was assessed until March 31, 2020. Among 743 053 individuals with T2D and 2 199 539 matched individuals without T2D, 126 241 incident HHF events occurred over 8.9 years. T2D was associated with a greater adjusted hazard of HHF at younger ages (eg, HR at age 30 years: 6.94 [95% CI, 6.54–7.36]) than at older ages (eg, HR at age 60 years: 2.50 [95% CI, 2.45–2.56]) relative to matched individuals. Additional adjustment for mediators (hypertension, coronary artery disease, and chronic kidney disease) marginally attenuated this relationship. Age at T2D diagnosis was associated with a greater number of HHF events relative to matched individuals at younger ages (eg, RR at age 30 years: 6.39 [95% CI, 5.76–7.08]) than at older ages (eg, RR at age 60 years: 2.65 [95% CI, 2.54–2.76]). Conclusions Younger age at T2D diagnosis is associated with a disproportionately elevated HHF risk relative to age‐matched individuals without T2D.

BackgroundThe burden of gestational diabetes (GDM) and the optimal screening strategies in African populations are yet to be determined. We assessed the prevalence of GDM and the performance of various screening tests in a Cameroonian population.MethodsWe carried out a cross-sectional study involving the screening of 983 women at 24-28 weeks of pregnancy for GDM using serial tests, including fasting plasma (FPG), random blood glucose (RBG), a 1-hour 50g glucose challenge test (GCT), and standard 2-hour oral glucose tolerance test (OGTT). GDM was defined using the World Health Organization (WHO 1999), International Association of Diabetes and Pregnancy Special Group (IADPSG 2010), and National Institute for Health Care Excellence (NICE 2015) criteria. GDM correlates were assessed using logistic regressions, and c-statistics were used to assess the performance of screening strategies.FindingsGDM prevalence was 5·9%, 17·7%, and 11·0% using WHO, IADPSG, and NICE criteria, respectively. Previous stillbirth [odds ratio: 3·14, 95%CI: 1·27-7·76)] was the main correlate of GDM. The optimal cut-points to diagnose WHO-defined GDM were 5·9 mmol/L for RPG (c-statistic 0·62) and 7·1 mmol/L for 1-hour 50g GCT (c-statistic 0·76). The same cut-off value for RPG was applicable for IADPSG-diagnosed GDM while the threshold was 6·5 mmol/L (c-statistic 0·61) for NICE-diagnosed GDM. The optimal cut-off of 1-hour 50g GCT was similar for IADPSG and NICE-diagnosed GDM. WHO-defined GDM was always confirmed by another diagnosis strategy while IADPSG and GCT independently identified at least 66·9 and 41·0% of the cases.InterpretationGDM is common among Cameroonian women. Effective detection of GDM in under-resourced settings may require simpler algorithms including the initial use of FPG, which could substantially increase screening yield.

Objective: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is a marker of cardiac wall stress and is a predictor of cardiovascular disease. Higher diet quality is associated with lower risk of cardiovascular disease. The association between diet quality and subclinical cardiovascular disease assessed by NT-proBNP is uncharacterized. We investigated the associations between diet quality, using Healthy Eating Index-2015 (HEI-2015), and NT-proBNP from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Methods: We included 9,782 adults from NHANES 1999-2004 without self-reported cardiovascular disease. The HEI-2015 ranges from 0 to 100, with higher scores indicating better diet quality. The HEI-2015 was categorized into sex-specific quintiles. Regression models were used to quantify associations between the overall HEI-2015 score and its 13 components with log-transformed NT-proBNP. The beta coefficients were converted to percent differences. Results: Among 9,782 participants, mean age was 45 years, 48% were men, and 72% were non-Hispanic White adults. After adjusting for sociodemographic characteristics, lifestyle factors, and medical history, those in the highest vs. lowest HEI-2015 quintile had an 8.5% (95% CI: -14.6% to -2.0%) lower NT-proBNP level. There was a dose-response association between HEI-2015 and NT-proBNP (P value for trend = 0.01). Each 1-unit higher in sodium and added sugars score indicating lower intake was associated with lower NT-proBNP by 7.7% (95% CI: -12.8% to -2.2%) and 6.5% (95% CI: -12.0% to -0.7%), respectively. Conclusion: Higher diet quality, especially lower intakes of sodium and added sugars, was associated with lower serum levels of NT-proBNP.

Background There is a paucity of large‐scale epidemiological studies on the link between cardiac autonomic neuropathy (CAN) and the risk of silent myocardial infarction (SMI) in type 2 diabetes. We evaluated the association between CAN and the risk of SMI in a large sample of adults with type 2 diabetes. Methods and Results Participants with type 2 diabetes from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without atherosclerotic cardiovascular disease at baseline were included. CAN was ascertained using heart rate variability indices calculated from 10‐s resting electrocardiograms. The heart rate variability indices included standard deviation of all normal‐to‐normal R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals. CAN was defined as both the standard deviation of all normal‐to‐normal R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals less than the fifth percentile of the general population. We used Cox proportional hazards regression to generate hazard ratios (HRs) for incident SMI in relation to CAN measures. Among 4842 participants (mean age, 62.5 years; 46.6% women; 60.2% White), there were 73 incident SMI cases over a median follow‐up of 4.9 years (incidence rate 3.1 out of 1000 person‐years [95% CI, 2.5–3.9]). After adjusting for confounders, low heart rate variability was associated with a higher risk of SMI (HR, 1.67 [95% CI, 1.02–2.72] and HR, 1.56 [95% CI, 0.94–2.58] for low standard deviation of all normal‐to‐normal R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals, respectively). Participants with CAN had a 1.9‐fold greater risk of SMI (HR, 1.91 [95% CI, 1.14–3.20]). Conclusions In a large cohort of adults with type 2 diabetes, CAN was significantly associated with an increased risk of incident SMI.

Background: The presence and interpretation of racial and ethnic differences in circulating N-terminal pro-brain-type natriuretic peptide (NT-proBNP), a diagnostic biomarker for heart failure, are controversial. Objective: To examine racial and ethnic differences in NT-proBNP levels among the general US adult population. Methods: We performed a cross-sectional analysis of data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES). We included 4717 non-Hispanic White, 1675 non-Hispanic Black, and 2148 Mexican American adults aged 20 years or older without a history of cardiovascular disease. We examined the associations of race and ethnicity with NT-proBNP using linear and logistic regression models in the overall population and in a younger, ‘healthy’ subsample. Results: The mean age was 45 years. Median NT-proBNP levels were significantly lower among Black (29.3 pg/mL) and Mexican American adults (28.3.4 pg/mL) compared to White adults (49.1pg/mL, P-values

Abstract Chronic kidney disease (CKD) in people with diabetes is becoming an increasing major public health concern, disproportionately burdening low- and middle-income countries (LMICs). This rising burden is due to various factors, including the lack of disease awareness that results in late referral and the cost of screening and consequent treatment of the comorbid conditions, as well as other factors endemic to LMICs relating to inadequate management of risk factors. We critically assessed the extant literature, by performing searches of Medline via PubMed, EBSCOhost, Scopus, and Web of Science, for studies pertaining to screening, diagnosis, and prediction of CKD amongst adults with diabetes in LMICs, using relevant key terms. The relevant studies were summarized through key themes derived from the Wilson and Jungner criteria. We found that screening for CKD in people with diabetes is generally infrequent in LMICs. Also, LMICs are ill-equipped to appropriately manage diabetes-associated CKD, especially its late stages, in which supportive care and kidney replacement therapy (KRT) might be required. There are acceptable and relatively simple tools that can aid diabetes-associated CKD screening in these countries; however, these tools come with limitations. Thus, effective implementation of diabetes-associated CKD screening in LMICs remains a challenge, and the cost-effectiveness of such an undertaking largely remains to be explored. In conclusion, for many compelling reasons, screening for CKD in people with diabetes should be a high policy priority in LMICs, as the huge cost associated with higher mortality and morbidity in this group and the cost of KRT offers a compelling economic incentive for improving early detection of diabetes in CKD.

Background NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) is strongly associated with mortality in patients with heart failure. Prior studies, primarily in middle‐aged and older populations, have suggested that NT‐proBNP has prognostic value in ambulatory adults. Methods and Results We conducted a prospective cohort analysis of adults, aged ≥20 years, in the nationally representative 1999 to 2004 National Health and Nutrition Examination Survey, to characterize the association of NT‐proBNP with mortality in the general US adult population overall and by age, race and ethnicity, and body mass index. We used Cox regression to characterize associations of NT‐proBNP with all‐cause and cardiovascular disease (CVD) mortality through 2019, adjusting for demographics and cardiovascular risk factors. We included 10 645 individuals (mean age, 45.7 years; 50.8% women; 72.8% White adults; 8.5% with a self‐reported history of CVD). There were 3155 deaths (1009 CVD‐related) over a median 17.3 years of follow‐up. Among individuals without prior CVD, elevated NT‐proBNP (≥75th percentile [81.5 pg/mL] versus 0.05). Conclusions In a representative sample of the US adult population, NT‐proBNP was an important independent risk factor for all‐cause and CVD mortality. NT‐proBNP may be useful for monitoring risk in the general adult population.

Background We characterized the burden and prognostic value of subclinical cardiovascular disease (CVD) assessed by cardiac biomarkers among adults with and without diabetes in the general US population. Methods and Results We measured hs‐cTnT (high‐sensitivity cardiac troponin T) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) in stored serum samples from the 1999 to 2004 National Health and Nutrition Examination Survey. Among US adults without a history of CVD (n=10 304), we estimated the prevalence of elevated hs‐cTnT (≥14 ng/L) and NT‐proBNP (≥125 pg/mL) in those with and without diabetes. We examined the associations between elevated hs‐cTnT and NT‐proBNP with all‐cause and CVD mortality after adjustment for demographics and traditional CVD risk factors. The crude prevalence of subclinical CVD (elevated hs‐cTnT or NT‐proBNP) was ≈2 times higher in adults with (versus without) diabetes (33.4% versus 16.1%). After age adjustment, elevated hs‐cTnT, but not elevated NT‐proBNP, was more common in those with diabetes, overall and across age, sex, race and ethnicity, and weight status. The prevalence of elevated hs‐cTnT was significantly higher in those with longer diabetes duration and worse glycemic control. In persons with diabetes, elevated hs‐cTnT and NT‐proBNP were independently associated with all‐cause mortality (adjusted hazard ratio [HR], 1.77 [95% CI, 1.33–2.34] and HR, 1.78 [95% CI, 1.26–2.51]) and CVD mortality (adjusted HR, 1.54 [95% CI, 0.83–2.85] and HR, 2.46 [95% CI, 1.31–4.60]). Conclusions Subclinical CVD affects ≈1 in 3 US adults with diabetes and confers substantial risk for mortality. Routine testing of cardiac biomarkers may be useful for assessing and monitoring risk in persons with diabetes.

Abstract Background Cardiovascular prognosis related to type 2 diabetes may not be adequately captured by information on comorbid conditions such as obesity and hypertension. To inform the cardiovascular prognosis among diabetic individuals, we conducted phenotyping using a clustering approach based on clinical data, echocardiographic indices and biomarkers. Methods We performed a cluster analysis on clinical, biochemical and echocardiographic variables from 529 Blacks with diabetes in the Jackson Heart Study. An association between identified clusters and major adverse cardiovascular events (MACE- composite of coronary heart disease, stroke, heart failure and atrial fibrillation) was assessed using Cox proportional hazards modeling. Results Cluster analysis separated individuals with diabetes (68% women, mean age 60 ± 10 years) into three distinct clusters (Clusters 1,2 &3 - with Cluster 3 being a hypertrophic cluster characterized by highest LV mass, levels of brain natriuretic peptide [BNP] and high-sensitivity cardiac troponin-I [hs-cTnI]). After a median 12.1 years, there were 141 cardiovascular events. Compared to Cluster1, Clusters 3 had an increased risk of cardiovascular disease (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.08, 2.37), while Cluster 2 had a similar risk of outcome (HR 1.11; 95% CI 0.73, 168). Conclusions Among Blacks with diabetes, cluster analysis identified three distinct echocardiographic and biomarkers phenotypes, with cluster 3 (high LV mass, high cardiac biomarkers) associated with worse outcomes, thus highlighting the prognostic value of subclinical myocardial dysfunction.

Background: Greater attainment of ideal cardiovascular health (ICH) and lower serum aldosterone are associated with lower diabetes risk. Higher levels of ICH are associated with lower aldosterone. The mediational role of aldosterone in the association of ICH with incident diabetes remains unexplored. Thus, we examined the mediational role of aldosterone in the association of 5 ICH components (smoking, diet, physical activity, body mass index [BMI], and cholesterol) with incident diabetes. Additionally, we investigated the mediational role of glucose and blood pressure (BP) in the association of aldosterone with incident diabetes in an African American (AA) cohort. Methods: We conducted a prospective cohort analysis among AA adults, aged 21–94 years, in the Jackson Heart Study. Data on ICH, aldosterone, and cardiometabolic risk factors were collected at exam 1 (2000–2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at exams 1 through 3 (2009–2012). ICH metrics were defined by American Heart Association 2020 goals for smoking, dietary intake, physical activity, BMI, total cholesterol, BP and glucose. The number of ICH metrics attained at exam 1, excluding BP and fasting glucose, were summed (0–2, vs. 3+). R Package Mediation was used to examine: 1) The mediational role of aldosterone in the association of ICH with incident diabetes; and 2) the mediational role of BP and glucose in the association of aldosterone with incident diabetes. Results: Among 2,791 participants (mean age: 53±12, 65% female) over a median of 7.5 years, there were 497 incident diabetes cases. Risk of incident diabetes was 37% (HR: 0.63, 95%CI: 0.47, 0.84) lower in 3+ ICH category compared to 0–2 ICH category. Aldosterone mediated 6.98% (95% CI: 1.8%, 18.0%) of the direct effect of ICH on incident diabetes. A 1-unit increase in log-aldosterone was associated with a 44% higher risk of diabetes (HR 1.44, 95%CI 1.25–1.64). BP and glucose mediated 16.3% (95% CI: 7.0%, 31.0%) and 19.7% (95% CI: 6.5%, 34.0%) of the association of aldosterone with incident diabetes, respectively. Conclusion: Aldosterone is a mediator of the association of ICH with incident diabetes, whereas BP and glucose are mediators of the association of aldosterone with incident diabetes, emphasizing the importance of the renin-angiotensin-aldosterone system and ICH in lowering risk of diabetes in AA populations.

Abstract Background Data on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes. Methods Participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories. Results A total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0–5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0–4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR

Abstract Background It remains unclear how the variability of adiposity indices relates to incident HF. This study evaluated the associations of the variability in several adiposity indices with incident heart failure (HF) in individuals with type 2 diabetes (T2DM). Methods We included 4073 participants from the Look AHEAD (Action for Health in Diabetes) study. We assessed variability of body mass index (BMI), waist circumference (WC), and body weight across four annual visits using three variability metrics, the variability independent of the mean (VIM), coefficient of variation (CV), and intraindividual standard deviation (SD). Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for incident HF. Results Over a median of 6.7 years, 120 participants developed incident HF. After adjusting for relevant confounders including baseline adiposity levels, the aHR for the highest (Q4) versus lowest quartile (Q1) of VIM of BMI was 3.61 (95% CI 1.91–6.80). The corresponding aHRs for CV and SD of BMI were 2.48 (95% CI 1.36–4.53) and 2.88 (1.52–5.46), respectively. Regarding WC variability, the equivalent aHRs were 1.90 (95% CI 1.11–3.26), 1.79 (95% CI 1.07–3.01), and 1.73 (1.01–2.95) for Q4 versus Q1 of VIM, CV and SD of WC, respectively. Conclusions In a large sample of adults with T2DM, a greater variability of adiposity indices was associated with higher risks of incident HF, independently of traditional risk factors and baseline adiposity levels. Registration-URL: https://clinicaltrials.gov/ct2/show/NCT00000620 .

There are limited data on the link between cardiac autonomic neuropathy (CAN) and severe hypoglycemia in type 2 diabetes. Here, we evaluated the associations of CAN with severe hypoglycemia among 7,421 adults with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes study. CAN was defined using ECG-derived measures. Cox’s and Andersen-Gill regression models were used to generate HRs (HRs) for the first and recurrent severe hypoglycemic episodes, respectively. Over 4.7 years, there were 558 first and 811 recurrent hypoglycemic events. Participants with CAN had increased risks of a first episode or recurrent episodes of severe hypoglycemia. The intensity of glycemic management modified the CAN association with hypoglycemia. In the standard glycemic management group, compared with those of participants without CAN, HRs for a first severe hypoglycemia event and recurrent hypoglycemia were 1.58 and 1.96, respectively. In the intensive glycemic management group, HRs for a first severe hypoglycemia event and recurrent hypoglycemia were 1.10 and 1.24, respectively. In summary, CAN was independently associated with higher risks of a first hypoglycemia event and recurrent hypoglycemia among adults with type 2 diabetes, with the highest risk observed among those on standard glycemic management.

Abstract Aims Data on the association of long‐term variability of blood pressure (BP) with incident heart failure (HF) in individuals with Type 2 diabetes are scarce. We evaluated this association in a large community‐based sample of adults with Type 2 diabetes. Methods and results A total of 4200 participants with Type 2 diabetes who had available BP measurements at four visits (baseline and 12, 24, and 36 months) in the Look AHEAD (Action for Health in Diabetes) study were included. Variability of systolic BP (SBP) and diastolic BP (DBP) across the four visits was assessed using four metrics. Participants free of HF during the first 36 months were followed for HF events. Cox regression was used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for HF. Of the 4200 participants, the average age was 59 years [standard deviation (SD): 6.8]; 58.5% were women. Over a median follow‐up of 6.7 years, 129 developed HF events. After adjusting for relevant confounders, the HR of incident HF for the highest vs. lowest quartile of SD of SBP was 1.77 (95% CI 1.01–3.09); the HR for the highest (vs. lowest) quartile of variability independent of the mean of SBP was 1.29 (95% CI 0.78–2.14). The adjusted HR for participants in the highest (compared with the lowest) quartile of SD of DBP was 1.61 (95% CI 1.01–2.59), and the adjusted HR for variability independent of the mean of DBP was 1.65 (95% CI 1.03–2.65). Conclusions A greater variability in SBP and DBP is independently associated with greater risk of incident HF in individuals with Type 2 diabetes.

Background Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin‐3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996–1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin‐3 (≥75th sex‐specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin‐3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin‐3 (odds ratio [OR], 2.32; 95% CI, 1.88–2.86) for severe obesity ([BMI ≥35 kg/m2] versus normal weight [BMI 18.5‐4‐fold higher risk of HF (HR, 4.19; 95% CI, 2.98–5.88) than those with normal weight and galectin‐3

Abstract Background Long-term exposure to pollution has been shown to increase risk of cardiovascular disease (CVD) and mortality, and may contribute to the increased risk of CVD among individuals with higher social risk. Methods Data from the community-based Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were used to quantify Cumulative Social Risk (CSR) by assigning a score of 1 for the presence of each of 4 social risk factors: racial minority, single living, low income, and low educational status. 1-year average air pollution exposure to PM2.5 was estimated using land-use regression models. Associations with clinical outcomes were assessed using Cox models, adjusting for traditional CVD risk factors. The primary clinical outcome was combined all-cause mortality and nonfatal CVD events. Results Data were available on 1933 participants (mean age 59 years, 66% female, 44% Black). In a median follow up time of 8.3 years, 137 primary clinical outcome events occurred. PM2.5 exposure increased with higher CSR score. PM2.5 was independently associated with clinical outcome (adjusted hazard ratio [HR]: 1.19 [95% CI: 1.00, 1.41]). Participants with ≥2 CSR factors had an adjusted HR of 2.34 (1.48–3.68) compared to those with CSR = 0. The association was attenuated after accounting for PM2.5 (HR: 2.16; [1.34, 3.49]). Mediation analyses indicate that PM2.5 explained 13% of the risk of clinical outcome in individuals with CSR score ≥ 2. Conclusion In a community-based cohort study, we found that the association of increasing CSR with higher CVD and mortality risks is partially accounted for by exposure to PM2.5 environmental pollutants.

Background Studies have reported that people living with HIV have higher burden of subclinical cardiovascular disease, but the data are not adequately synthesized. We performed meta‐analyses of studies of coronary artery calcium and coronary plaque in people living with HIV. Methods and Results We performed systematic search in electronic databases, and data were abstracted in standardized forms. Study‐specific estimates were pooled using meta‐analysis. 43 reports representing 27 unique studies and involving 10 867 participants (6699 HIV positive, 4168 HIV negative, mean age 52 years, 86% men, 32% Black) were included. The HIV‐positive participants were younger (mean age 49 versus 57 years) and had lower Framingham Risk Score (mean score 6 versus 18) compared with the HIV‐negative participants. The pooled estimate of percentage with coronary artery calcium >0 was 45% (95% CI, 43%–47%) for HIV‐positive participants, and 52% (50%–53%) for HIV‐negative participants. This difference was no longer significant after adjusting for difference in Framingham Risk Score between the 2 groups. The odds ratio of coronary artery calcium progression for HIV‐positive versus ‐negative participants was 1.64 (95% CI, 0.91–2.37). The pooled estimate for prevalence of noncalcified plaque was 49% (95% CI, 47%–52%) versus 20% (95% CI, 17%–23%) for HIV‐positive versus HIV‐negative participants, respectively. Odds ratio for noncalcified plaque for HIV‐positive versus ‐negative participants was 1.23 (95% CI, 1.08–1.38). There was significant heterogeneity that was only partially explained by available study‐level characteristics. Conclusions People living with HIV have higher prevalence of noncalcified coronary plaques and similar prevalence of coronary artery calcium, compared with HIV‐negative individuals. Future studies on coronary artery calcium and plaque progression can further elucidate subclinical atherosclerosis in people living with HIV.

Background The prognostic value of anthropometric, adipokine, and computed tomography measures of adiposity to predict diabetes in Black, specifically by normoglycemia versus prediabetes, remains incompletely understood. Methods and Results Among Black participants without diabetes in the JHS (Jackson Heart Study), waist circumference [WC], body mass index, adiponectin, leptin, and leptin:adiponectin ratio were standardized in sample 1 (2422 participants at baseline [2000–2004]) and WC, body mass index, visceral adipose tissue (VAT), subcutaneous adipose tissue, and liver attenuation in 1537 participants at examination 2 (2005–2008) (sample 2). Hazard ratios (HRs) for diabetes were estimated using interval‐censored Cox modeling adjusting for traditional risk factors and validated with the C index. Over 5 years, 300 and 122 incident diabetes cases occurred in sample 1 and sample 2, respectively. In sample 1 and sample 2, a 1‐SD higher log‐leptin:adiponectin ratio and VAT had the strongest associations (HR, 1.95 [95% CI, 1.67–2.27] and 1.76 [95% CI, 1.52–2.04]) and discriminatory power (C index 0.68 [95% CI, 0.64–0.71] and C index 0.67 [95% CI, 0.61–0.74]) with diabetes. The normoglycemic compared with the prediabetes group had a 1.3 to 1.9 times greater magnitude of associations with diabetes for WC, liver attenuation, and VAT (P interaction

Background Microvascular disease (MVD) is a potential contributor to the pathogenesis of diabetes mellitus–related cardiac dysfunction. However, there is a paucity of data on the link between MVD and incident heart failure (HF) in type 2 diabetes mellitus. We examined the association of MVD with incident HF in adults with type 2 diabetes mellitus. Methods and Results A total of 4095 participants with type 2 diabetes mellitus and free of HF were assessed for diabetes mellitus–related MVD including nephropathy, retinopathy, or neuropathy at baseline in the Look AHEAD (Action for Health in Diabetes) study. Incident HF events were prospectively assessed and adjudicated using hospital and death records. Cox models were used to generate hazard ratios and 95% CIs for HF. Of 4095 participants, 34.8% (n=1424) had MVD, defined as the presence of ≥1 of nephropathy, retinopathy, or neuropathy at baseline. Over a median of 9.7 years, there were 117 HF events. After adjusting for relevant confounders, participants with MVD had a 2.5‐fold higher risk of incident HF than those without MVD (hazard ratio, 2.54; 95% CI, 1.73–3.75). This association remained significant after additional adjustment for interval development of coronary artery disease (hazard ratio, 2.42; 95% CI, 1.64–3.57). The hazard ratios for HF by type of MVD were 2.22 (95% CI, 1.51–3.27), 1.30 (95% CI, 0.72–2.36), and 1.33 (95% CI, 0.86–2.07) for nephropathy, retinopathy, and neuropathy, respectively. CONCLUSIONS MVD is associated with an excess HF risk in individuals with type 2 diabetes mellitus after adjusting for other known risk factors. Our findings underscore the contribution of MVD to the development of diabetes mellitus–related HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00017953.

Background Metabolic dyslipidemia (high triglyceride) and low high‐density lipoprotein cholesterol (HDL‐C) is highly prevalent in type 2 diabetes mellitus (T2DM). The extent to which diabetes mellitus–related abnormalities in the triglyceride–HDL‐C profile associates with cardiovascular disease (CVD) risk is incompletely understood. We evaluated the associations of triglyceride and HDL‐C status with CVD outcomes in individuals with T2DM. Methods and Results We analyzed data from 4199 overweight/obese adults with T2DM free of CVD with available data on triglyceride and HDL‐C at baseline (2001–2004) in the Look AHEAD (Action for Health in Diabetes) study. We used Cox proportional models to estimate hazard ratios (HRs) and 95% CIs of: (1) composite CVD outcome (myocardial infarction, stroke, hospitalization for angina, and/or death from cardiovascular causes); (2) coronary artery disease events; and (3) cerebrovascular accidents (stroke). Of the 4199 participants, 62% (n=2600) were women, with a mean age of 58 years (SD, 7), and 40% (n=1659) had metabolic dyslipidemia at baseline. Over a median follow‐up of 9.5 years (interquartile range, 8.7–10.3), 500 participants experienced the composite CVD outcome, 396 experienced coronary artery disease events, and 100 experienced stroke. Low HDL‐C was associated with higher hazards of the composite CVD outcome (HR, 1.36; 95% CI, 1.12–1.64 [P=0.002]) and coronary artery disease events (HR, 1.46; 95% CI, 1.18–1.81 [P=0.001]) but not stroke (HR, 1.38; 95% CI, 0.90–2.11 [P=0.140]). Compared with patients with normal triglyceride and normal HDL, participants with metabolic dyslipidemia had higher risks of the composite CVD outcome (HR, 1.30; 95% CI, 1.03–1.63 [P=0.025]) and coronary artery disease events (HR, 1.48; 95% CI, 1.14–1.93 [P=0.003]) but not stroke (HR, 1.23; 95% CI, 0.74–2.05 [P=0.420]). Conclusions In a large sample of overweight/obese individuals with T2DM, metabolic dyslipidemia was associated with higher risks of CVD outcomes. Our findings highlight the necessity to account for metabolic dyslipidemia in CVD risk stratification among patients with T2DM. Registration URL: https://www.lookaheadtrial.org; Unique identifier: NCT00017953.

Abstract Background Accurate contemporary data on the burden of Chronic Kidney Disease (CKD) on the African continent are lacking. We determined the prevalence of CKD in adult populations living in Africa, and variations by stage, gender, estimated Glomerular Filtration Rate (eGFR) equation, and residence. Methods For this systematic review, we searched multiple electronic databases for original studies on CKD prevalence reported from January 1, 2000 to December 31, 2016. Two reviewers independently undertook quality assessment and data extraction. We stabilized the variance of study-specific estimates with the Freeman-Turkey single arcsine transformation and pooled the data using a random effects meta-analysis models. Results A total of 98 studies involving 98,432 individuals were included in the final meta-analysis. The overall prevalence was 15.8% (95% CI 12.1–19.9) for CKD stages 1–5 and 4.6% (3.3–6.1) for CKD stages 3–5 in the general population. Equivalent figures were greater at 32.3% (23.4–41.8) and 13.3% (10.7–16.0) in high-risk populations (people with hypertension, diabetes, HIV). CKD prevalence was higher in studies based on the Cockcroft-Gault formula than MDRD or CKD-EPI equations; and in studies from sub-Saharan Africa compared with those from North Africa (17.7, 95% CI 13.7–22.1 vs 6.1, 95% CI 3.6–9.3, p 90%) and no evidence of publication bias in main analyses. Conclusion CKD is highly prevalent across Africa, inviting efforts into prevention, early detection and control of CKD in adults living on the African continent which is particularly important in a resource limited environment. Trial Registration Prospero Registration ID: CRD42017054445.

Abstract Background Quantifying the cumulative effect of social risk factors on cardiovascular disease (CVD) risk can help to better understand the sources of disparities in health outcomes. Method and results Data from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were used to create an index of cumulative social risk (CSR) and quantify its association with incident CVD and all-cause mortality. CSR was defined by assigning a score of 1 for the presence of each of 4 social factors: i) racial minority status (Black race), ii) single living status, iii) low income, and iv) low educational level. Hazard ratios (HRs) were computed using Cox-regression models, adjusted for CVD risk factors. Over a median follow-up period of 8.3 years, 127 incident events were observed. The incidence of the primary outcome for subgroups of participants with 0, 1, and ≥2 CSR scores was 5.31 (95% CI, 3.40–7.22), 10.32 (7.16–13.49) and 17.80 (12.94–22.67) per 1000 person-years, respectively. Individuals with CSR score of 1 had an adjusted HR of 1.85 (1.15–2.97) for incident primary outcomes, compared to those with score of 0. The corresponding HR for individuals with CSR score of 2 or more was 2.58 (1.60–4.17). Conclusion An accumulation of social risk factors independently increased the likelihood of CVD events and deaths in a cohort of White and Black individuals.

ABSTRACT: Objective: To demonstrate important points regarding the possible hypoglycemic effects of sulfasalazine and suggest possible underlying mechanism(s) accounting for sulfasalazine-induced hypoglycemia.Methods: We describe a case of reversible sulfasalazine-induced hypoglycemia, review the literature, and discuss a potential mechanism accounting for sulfasalazine-induced hypoglycemia.Results: A 63-year-old man with Crohn disease treated with sulfasalazine and type 2 diabetes complicated by end-stage renal disease was admitted for treatment of persistent hypoglycemia. Insulinoma was initially suspected, but localization studies including endoscopic ultrasound were negative. This raised the possibility of sulfasalazine-induced hypoglycemia. Three days after sulfasalazine was stopped, he became normoglycemic. Hypoglycemia has not recurred since discontinuing sulfasalazine.Conclusion: Clinicians should be aware of the potential hypoglycemic effect of sulfasalazine. Doses should be reduced in patients with impaired renal function, and it should be discontinued if otherwise unexplained hypoglycemia develops.Abbreviations: CT = computed tomography; ESRD = end-stage renal disease

BackgroundThe concept of ideal cardiovascular health (CVH), defined by the American Heart Association primarily for coronary heart disease and stroke prevention, may apply to diabetes mellitus prevention among blacks. Methods and ResultsOur sample included 2668 adults in the Jackson Heart Study with complete baseline data on 6 of 7 American Heart Association CVH metrics (body mass index, healthy diet, smoking, total cholesterol, blood pressure, and physical activity). Incident diabetes mellitus was defined as fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes mellitus drugs, or glycosylated hemoglobin ≥6.5%. A summary CVH score from 0 to 6, based on presence/absence of ideal CVH metrics, was derived for each participant. Cox regression was used to estimate adjusted hazard ratios. Mean age was 55 years (65% women) with 492 incident diabetes mellitus events over 7.6 years (24.6 cases/1000 person‐years). Three quarters of participants had only 1 or 2 ideal CVH metrics; no participant had all 6. After adjustment for demographic factors (age, sex, education, and income) and high‐sensitivity C‐reactive protein, each additional ideal CVH metric was associated with a 17% diabetes mellitus risk reduction (hazard ratio, 0.83; 95% CI, 0.74–0.93). The association was attenuated with further adjustment for homeostasis model assessment for insulin resistance (hazard ratio, 0.89; 95% CI, 0.79–1.00). Compared with participants with 1 or no ideal CVH metric, diabetes mellitus risk was 15% and 37% lower in those with 2 and ≥3 ideal CVH metrics, respectively. ConclusionsThe AHA concept of ideal CVH is applicable to diabetes mellitus prevention among blacks. These associations were largely explained by insulin resistance.