Metabolic dysfunction and incidence of heart failure subtypes among Black individuals: The Jackson Heart Study.

AIMS: The extent to which metabolic syndrome (MetS) severity influences subclinical myocardial remodelling, heart failure (HF) incidence and subtypes, remains unclear. We assessed the association of MetS with incident HF (including ejection fraction subtypes) among Black individuals. METHODS AND RESULTS: We included 4069 Jackson Heart Study participants (mean age 54.4 years, 63.8% women, 37.2% with MetS) without HF. We categorized participants based on MetS status and MetS severity scores (based on waist circumference [MetS-Z-WC] and body mass index [MetS-Z-BMI]). We assessed the associations of MetS indices with echocardiographic parameters, biomarkers of myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI] and B-type natriuretic peptide [BNP]) and incident HF hospitalizations including HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). MetS severity was associated with subclinical cardiac remodelling (assessed by echocardiographic measures and biomarkers of myocardial damage). Over a median of 12 years, 319 participants developed HF (157 HFpEF, 149 HFrEF and 13 HF of unknown type). MetS was associated with a twofold greater risk of HF (hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.64-2.61). Compared to the lowest quartile (Q1) of MetS-Z-WC, the highest quartile (Q4) conferred a higher risk of HF (HR 2.35, 95% CI 1.67-3.30), with a stronger association for HFpEF (Q4 vs. Q1: HR 4.94, 95% CI 2.67-9.14) vs. HFrEF (HR 1.69, 95% CI 1.06-2.70). CONCLUSIONS: Metabolic syndrome severity was associated with both HF subtypes among Black individuals, highlighting the importance of optimal metabolic health for preventing HF.

Association of ideal cardiovascular health and history of gestational diabetes mellitus in NHANES 2007-2018.

BACKGROUND: Population-based studies of ideal cardiovascular health (CVH) and gestational diabetes mellitus (GDM) are scarce. METHODS: We conducted a cross-sectional analysis of 2007-2018 National Health Examination and Nutrition Survey women aged ≥ 20 years, who had data on Life's Simple 7 (LS7) metrics and self-reported GDM history. Each LS7 metric was assigned a score of 0 (non-ideal) and 1(ideal) and summed to obtain total ideal CVH scores (0-7). We used logistic regression models to assess associations between LS7 ideal CVH scores (0-7) and GDM history, accounting for socio-demographic factors. RESULTS: Among 9199 women (mean age: 46 years, 8 % with a GDM history), there was a progressive decrease in the odds of past GDM history across increasing ideal CVH scores. Compared to females with 0-1 ideal CVH scores, females with ideal CVH scores of 3, 4 and 5-7 had an associated 39 % lower [odds ratio: 0.61 (95 % CI: 0.41-0.90)], 50 % lower [0.50 (0.33-0.76)] and 66 % lower [0.34 (0.20-0.56)] odds of past GDM history, respectively. There were notable racial/ethnic and citizenship/nativity differences in these associations. CONCLUSIONS: Women with higher ideal CVH scores had lower odds of GDM history. Our findings underscore the importance of optimizing cardiometabolic health among women with GDM history.

Trends in direct health care costs among US adults with atherosclerotic cardiovascular disease with and without diabetes.

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.

Health Care Expenditure in United States Adults With Heart Failure With and Without Diabetes.

The health costs for heart failure (HF) in patients with and without diabetes can help us understand the conjoint burden of diabetes and HF. Using the 2008 to 2019 US national Medical Expenditure Panel Survey data including 2,019 adults with HF and a 2-part adjusted model, we estimated the mean and adjusted incremental direct medical expenditures related to diabetes. The total direct expenditures for patients with HF increased by 27 %: $24,725 (95 % confidence interval [CI] $20,457 to $28,993) in 2008 to 2009 to $31,426 (95 % CI $25,705 to $37,147) in 2018 to 2019. The expenditures increased by 34 % in those with diabetes. Inpatient costs represented the highest fraction of costs ∼43.3 % and were 8 % higher in those with diabetes versus those without diabetes. The drug costs accounted for 24 % of all costs, increased by 44 %, and were 86 % higher in patients with HF with diabetes versus those without diabetes. The adjusted excess costs in patients with HF and diabetes versus HF without diabetes was $6,818 (95 % CI 2,241 to 11,395); the corresponding excess costs for drugs and medical costs other than drugs were $3,297 (95 % CI 2,168 to 4,426) and $3,554 (95 % CI -777 to 7,886). In US adults with HF, the estimated adjusted total direct excess costs were $5.2 billion per year higher in patients with diabetes versus those without diabetes. In conclusion, diabetes is associated with substantially increased health care costs in patients with HF, suggesting the need for an integrated management of diabetes and HF.

Integrated image-based deep learning and language models for primary diabetes care.

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening.

Association Between Microvascular Disease and Cardiorespiratory Fitness Among Adults With Type 2 Diabetes.

OBJECTIVE: Little is known about the extent to which microvascular disease is associated with cardiorespiratory fitness (CRF) among individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 4,766 participants with type 2 diabetes underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study at baseline. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Microvascular disease was defined as having one or more of diabetes-related kidney disease (DKD), retinopathy, and neuropathy. The burden of microvascular disease was defined as the number of microvascular beds affected. RESULTS: Of the 4,766 participants (mean age 58.9 ± 6.7 years, 58.5% women, 66.1% White individuals), 1,761 (37%) had microvascular disease. Participants with microvascular complications in three vascular territories had a lower CFR than those without any microvascular disease (mean adjusted metabolic equivalent of task [MET] 6.58 vs. 7.26, P = 0.001). Participants with any microvascular disease had higher odds of low CRF than those without microvascular disease (adjusted odds ratio [OR] 1.45, 95% CI 1.24-1.71). An increasing burden of microvascular disease was associated with higher odds of low CRF (for microvascular disease in three vascular territories, adjusted OR 2.82, 95% CI 1.36-5.85). Adjusted ORs for low CRF were 1.24 (95% CI 0.99-1.55), 1.34 (95% CI 1.02-1.76), and 1.44 (95% CI 1.20-1.73) for neuropathy, retinopathy, and DKD associations, respectively. CONCLUSIONS: In a large cohort of adults with type 2 diabetes, the presence of microvascular disease and its burden were independently associated with lower CRF.

Design and rationale of the cardiometabolic health program linked with community health workers and mobile health telemonitoring to reduce health disparities (LINKED-HEARTS) program.

BACKGROUND: Hypertension and diabetes are major risk factors for cardiovascular diseases, stroke, and chronic kidney disease (CKD). Disparities in hypertension control persist among Black and Hispanic adults and persons living in poverty in the United States. The "LINKED-HEARTS Program" (a Cardiometabolic Health Program LINKED with Community Health WorkErs and Mobile HeAlth TelemonitoRing To reduce Health DisparitieS"), is a multi-level intervention that includes home blood pressure (BP) monitoring (HBPM), blood glucose telemonitoring, and team-based care. This study aims to examine the effect of the LINKED-HEARTS Program intervention in improving BP control compared to enhanced usual care (EUC) and to evaluate the reach, adoption, sustainability, and cost-effectiveness of the program. METHODS: Using a hybrid type I effectiveness-implementation design, 428 adults with uncontrolled hypertension (systolic BP ≥ 140 mm Hg) and diabetes or CKD will be recruited from 18 primary care practices, including community health centers, in Maryland. Using a cluster-randomized trial design, practices are randomly assigned to the LINKED-HEARTS intervention arm or EUC arm. Participants in the LINKED-HEARTS intervention arm receive training on HBPM, BP and glucose telemonitoring, and community health worker and pharmacist telehealth visits on lifestyle modification and medication management over 12 months. The primary outcome is the proportion of participants with controlled BP (<140/90 mm Hg) at 12 months. CONCLUSIONS: The study tests a multi-level intervention to control multiple chronic diseases. Findings from the study may be leveraged to reduce disparities in the management and control of chronic diseases and make primary care more responsive to the needs of underserved populations. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT05321368.

Evolution and prognosis of tricuspid and mitral regurgitation following cardiac implantable electronic devices: a systematic review and meta-analysis.

AIMS: Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIEDs) are increasingly recognized. However, uncertainty remains as to whether the risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared with cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). The study aims to synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS AND RESULTS: We searched PubMed, EMBASE, and Cochrane Library databases published until 31 October 2023. Significant post-CIED TR and MR were defined as ≥ moderate. Fifty-seven TR studies (n = 13 723 patients) and 90 MR studies (n = 14 387 patients) were included. For all CIED, the risk of post-CIED TR increased [pooled odds ratio (OR) = 2.46 and 95% CI = 1.88-3.22], while the risk of post-CIED MR reduced (OR = 0.74, 95% CI = 0.58-0.94) after 12 and 6 months of median follow-up, respectively. Right ventricular pacing via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR = 4.54, 95% CI = 3.14-6.57) and post-CIED MR (OR = 2.24, 95% CI = 1.18-4.26). Binarily, CSP did not alter TR risk (OR = 0.37, 95% CI = 0.13-1.02), but significantly reduced MR (OR = 0.15, 95% CI = 0.03-0.62). Cardiac resynchronization therapy did not significantly change TR risk (OR = 1.09, 95% CI = 0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR = 0.49, 95% CI = 0.40-0.61). There was no significant association of LP with post-CIED TR (OR = 1.15, 95% CI = 0.83-1.59) or MR (OR = 1.31, 95% CI = 0.72-2.39). Cardiac implantable electronic device-associated TR was independently predictive of all-cause mortality [pooled hazard ratio (HR) = 1.64, 95% CI = 1.40-1.90] after median of 53 months. Mitral regurgitation persisting post-CRT independently predicted all-cause mortality (HR = 2.00, 95% CI = 1.57-2.55) after 38 months. CONCLUSION: Our findings suggest that, when possible, adoption of pacing strategies that avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.

Associations between hysterectomy and metabolic syndrome: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Metabolic syndrome is linked to an increased risk of incident cardiovascular disease and all-cause mortality. Notable associations exist between hysterectomy with bilateral salpingo-oophorectomy and metabolic syndrome. However, there is emerging evidence that even with ovarian conservation, hysterectomy may be independently associated with long-term cardiovascular disease risk. OBJECTIVE: To examine the associations between hysterectomy with ovarian preservation and metabolic syndrome risk in a multiethnic cohort. STUDY DESIGN: We studied 3367 female participants in the Multi-Ethnic Study of Atherosclerosis who had data on self-reported history of hysterectomy, oophorectomy, hystero-oophorectomy, and metabolic syndrome at baseline (2000-2002). We used adjusted logistic regression to assess the cross-sectional associations between hysterectomy and or oophorectomy subgroups and prevalent metabolic syndrome at baseline. Furthermore, we investigated 1355 participants free of baseline metabolic syndrome and used adjusted Cox regression models to evaluate incident metabolic syndrome from examinations 2 (2002-2004) to 6 (2016-2018). RESULTS: The mean age was 59.0±9.5 years, with 42% White, 27% Black, 19% Hispanic, and 13% Chinese American participants. 29% and 22% had a history of hysterectomy and oophorectomy, respectively. Over a median follow-up of 10.5 (3.01-17.62) years, there were 750 metabolic syndrome events. Hysterectomy (hazard ratio, 1.32 [95% confidence interval, 1.01-1.73]) and hystero-oophorectomy (hazard ratio, 1.40 [95% confidence interval, 1.13-1.74]) were both associated with incident metabolic syndrome compared with having neither hysterectomy nor oophorectomy. CONCLUSION: Hysterectomy, even with ovarian preservation, may be independently associated with a higher risk of metabolic syndrome. If other studies confirm these findings, screening and preventive strategies focused on females with ovary-sparing hysterectomies and the mechanisms underpinning these associations may be explored.

Galectin-3, Metabolic Risk, and Incident Heart Failure: The ARIC Study.

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.

Systemic and organ-specific anti-inflammatory effects of sodium-glucose cotransporter-2 inhibitors.

Inflammation plays an essential role and is a common feature in the pathogenesis of many chronic diseases. The exact mechanisms through which sodium-glucose cotransporter-2 (SGLT2) inhibitors achieve their much-acclaimed clinical benefits largely remain unknown. In this review, we detail the systemic and tissue- or organ-specific anti-inflammatory effects of SGLT2 inhibitors using evidence from animal and human studies. We discuss the potential pathways through which SGLT2 inhibitors exert their anti-inflammatory effects, including oxidative stress, mitochondrial, and inflammasome pathways. Finally, we highlight the need for further investigation of the extent of the contribution of the anti-inflammatory effects of SGLT2 inhibition to improvements in cardiometabolic and renal outcomes in clinical studies.

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Association Between Age at Diagnosis of Type 2 Diabetes and Hospitalization for Heart Failure: A Population-Based Study.

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.

Persistence of significant secondary mitral regurgitation post-cardiac resynchronization therapy and survival: a systematic review and meta-analysis : Mitral regurgitation and mortality post-CRT.

Cardiac resynchronization therapy (CRT) significantly reduces secondary mitral regurgitation (MR) in patients with severe left ventricular systolic dysfunction. However, uncertainty remains as to whether improvement in secondary MR correlates with improvement with mortality seen in CRT. We conducted a meta-analysis to determine the association of persistent unimproved significant secondary MR (defined as moderate or moderate-to-severe or severe MR) compared to improved MR (no MR or mild MR) post-CRT with all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A systematic search of PubMed, EMBASE, and Cochrane Library databases till July 31, 2022 identified studies reporting clinical outcomes by post-CRT secondary MR status. In 12 prospective studies of 4954 patients (weighted mean age 66.8 years, men 77.8%), the median duration of follow-up post-CRT at which patients were re-evaluated for significant secondary MR was 6 months and showed significant relative risk reduction of 30% compared to pre-CRT. The median duration of follow-up post-CRT for ascertainment of main clinical outcomes was 38 months. The random effects pooled hazard ratio (95% confidence interval) of all-cause mortality in patients with unimproved secondary MR compared to improved secondary MR was 2.00 (1.57-2.55); p < 0.001). There was insufficient data to evaluate secondary outcomes in a meta-analysis, but limited data that examined the relationship showed significant association of unimproved secondary MR with increased cardiovascular mortality and heart failure hospitalization. The findings of this meta-analysis suggest that lack of improvement in secondary MR post-CRT is associated with significantly elevated risk of all-cause mortality and possibly cardiovascular mortality and heart failure hospitalization. Future studies may investigate approaches to address persistent secondary MR post-CRT to help improved outcome in this population.

Cardiac Autonomic Dysfunction and Risk of Silent Myocardial Infarction Among Adults With Type 2 Diabetes.

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.

Insulin Resistance and N-Terminal Pro-B-Type Natriuretic Peptide Among Healthy Adults.

Importance: It is unclear to what extent insulin resistance is associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the general population after accounting for body composition. Objective: To characterize the association of insulin resistance with NT-proBNP independently of measures of body composition in US adults. Design, Setting, and Participants: In a cross-sectional design, data on participants aged 20 years or older were obtained from the 1999-2004 National Health and Nutrition Examination Survey with measures of NT-pro-BNP, body mass index (BMI), and dual energy x-ray absorptiometry (DEXA)-derived measures of body composition (fat and lean masses). Linear and logistic regression was used to characterize the associations of measures of body mass and composition (BMI, waist circumference, fat mass, and lean mass) with NT-proBNP, adjusting for cardiovascular risk factors. Linear regression was used to characterize the associations of homeostasis model assessment of insulin resistance [HOMA-IR] and NT-proBNP after adjusting for cardiovascular risk factors and body composition measures. The quantitative insulin sensitivity check index [QUICKI], triglyceride-glucose index [TyG index], insulin to glucose ratio [IGR], fasting insulin, and homeostasis model assessment of ß-cell function (HOMA-ß) were also examined. Data for this study were analyzed from August 10, 2022, to June 30, 2023. Main Outcomes and Measures: Adjusted changes in NT-proBNP by insulin resistance levels. Results: A total of 4038 adults without diabetes or cardiovascular disease were included (mean [SD] age, 44 years; 51.2% female; and 74.3% White). In sex-specific analyses, insulin resistance measures were inversely associated with NT-pro-BNP. After adjustment including cardiovascular risk factors, BMI, waist circumference, and DEXA-derived fat mass and lean mass, the percent change in NT-proBNP associated with an SD increase in HOMA-IR was -16.84% (95% CI, -21.23% to -12.21%) in women and -19.04% (95% CI, -24.14 to -13.59) in men. Similar associations were observed for other indices of insulin resistance, including QUICKI (women: 17.27; 95% CI, 10.92-23.99 vs men: 22.17; 95% CI, 15.27 to 29.48), TyG index women: -11.47; 95% CI, -16.12 to -6.57 vs men: -15.81; 95% CI, -20.40 to -10.95), IGR women: -15.15; 95% CI, -19.35 to -10.74 vs men: -16.61; 95% CI, -21.63 to -11.26), and fasting insulin (women: -16.32; 95% CI, -20.63 to -11.78 vs men: -18.22; 95% CI, -23.30 to -12.79), as well as HOMA-ß (women: -10.71; 95% CI, -14.71 to -6.52 vs men: -11.72; 95% CI, -16.35 to -6.85). Conclusions and Relevance: In a national sample of US adults, insulin resistance was inversely associated with NT-proBNP, even after rigorously accounting for multiple measures of fat mass and lean mass. These results suggest that the mechanisms linking NT-proBNP to insulin resistance are partially independent of excess adiposity and may be associated with hyperinsulinemia.