Impaired left ventricular systolic synchrony in patients with lupus Nephritis: A speckle tracking echocardiography study.

OBJECTIVES: We aimed to explore the value of two-dimensional speckle tracking echocardiography measurements of the global longitudinal strain (GLS) and left ventricular mechanical dispersion (LVMD) in the assessment of early stage left ventricular systolic dysfunction and heterogeneity of myocardial contraction in patients with lupus nephritis (LN). METHODS: Patients with LN and extra-renal systemic lupus erythematosus (SLE) and healthy participants in the control group underwent echocardiography for the traditional measurement of the left ventricular systolic and diastolic function and speckle tracking measurements of the GLS and LVMD. GLS was defined as the average value of the peak strain during systole of the left ventricular 17 segments, and LVMD was defined as the standard deviation. The demographic characteristics including age, sex, and body mass index (BMI) of all the participants were collected. The clinical and laboratory characteristics of the patients with LN were collected. RESULTS: We included 41 healthy control, 37 patients with extra-renal SLE, and 73 patients with LN. There were statistically significant differences in the GLS and LVMD between the extra-renal SLE and LN groups (GLS -19.36% vs. -17.61%, p < 0.001; LVMD 35.62 ms vs 42.96 ms, p<0.001). There was a statistically significant difference in the LVMD between the extral-renal SLE and control groups (35.62ms vs 25.51ms, p<0.001), but not in GLS (-19.36% vs -19.52%, p > 0.05). Multiple regression analyses were conducted in a subset of patients, and 24-hour proteinuria was independently associated with LVMD (ß [SE], 0.793 [0.302], p < .05). CONCLUSIONS: Patients with LN have more severe myocardial involvement than patients with extra-renal SLE. The asynchrony in myocardial contraction represented by the LVMD can be recognized earlier than that of the overall contractile functional impairment represented by GLS. In patients with LN, the 24-hour proteinuria was associated with LVMD. This indicates that the heterogeneity in the contractile function may be associated with the severity of renal damage.

Postsystolic shortening and early systolic lengthening for early detection of myocardial involvement in patients with systemic lupus erythematosus.

BACKGROUND: Cardiac involvement predicts a poor prognosis in patients with systemic lupus erythematosus (SLE). Two-dimensional speckle-tracking echocardiography (2D-STE) are used to identify subclinical myocardial involvement in various diseases. This study objected to evaluate postsystolic shortening (PSS) and early systolic lengthening (ESL) by 2D-STE for early detection of myocardial involvement in patients with SLE. METHODS: A total of 121 patients with preserved left ventricular ejection fraction (LVEF) in SLE and 30 healthy controls underwent standard 2D-STE in our study. According to SLE disease activity index (SLEDAI), we divided SLE patients into two groups: the group of inactive disease (SLEDAI ≤ 4) and active disease (SLEDAI ≥ 5). The maximum of postsystolic strain index (PSImax ) and early systolic strain index (ESImax ) were acquired from 17 segments of left ventricular (LV). We also compared the PSImax and ESImax of basal, medial, and apical segments between SLE patients and controls. RESULTS: Compared with healthy controls and the group of SLEDAI ≤ 4, the group of SLEDAI ≥ 5 had higher PSImax and ESImax value of global LV and basal segments. The absolute value of global longitudinal strain (GLS) had no difference between the group of active disease and inactive disease. Multivariate analysis demonstrated that PSS was independently associated with SLEDAI and diabetes mellitus. CONCLUSIONS: Detection of PSS and ESL enable to identify LV systolic impairment in SLE patients at an early stage.

An appraisal of clinical practice guidelines for the appropriate use of echocardiography for adult infective endocarditis-the timing and mode of assessment (TTE or TEE).

BACKGROUND: Echocardiography (echo) is the primary imaging modality for infective endocarditis (IE). However, the recommendations on timing and mode selection for transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) vary across guidelines, which can be confusing for clinical decision makers. In this case, we aim to appraise the quality of recommendations by appraising the quality of various guidelines. METHODS: A search of guidelines containing recommendations for the appropriate use of echo in adult IE patients published in English between 2007 and 2019 was conducted. The APPRAISAL OF GUIDELINES FOR RESEARCH & EVALUATION II (AGREE II) instrument was applied independently by two reviewers to assess the integrated quality of the identified guidelines. The recommendations of concern are extracted from related chapters. RESULTS: A total of 9 guidelines met the criteria, with AGREE II scores ranging from 36 to 79%, and the domain of "stakeholder involvement" received the lowest score. The most contentious issue is whether a follow-up TEE is mandatory in uncomplicated native valve IE with an initial positive TTE. Conflicting recommendations are presented with a low evidence level based on little evidence. CONCLUSIONS: In general, the recommendations proposed in the 9 identified guidelines on the appropriate use of echo are satisfying. The guideline quality score can be taken into account by the clinicians when evaluating the recommendations for clinical decisions. Additional studies with high evidence level should be conducted on the most controversial issues of whether a subsequent TEE is mandatory in uncomplicated native valve IE with an initial positive TTE.

A promising structural magnetic resonance imaging assessment in patients with preclinical cognitive decline and diabetes mellitus.

Subjective cognitive decline (SCD) is frequently reported in diabetic patients. Diabetes mellitus (DM) is associated with changes in the microstructure of the brain arise in diabetic patients, including changes in gray matter volume (GMV). However, the underlying mechanisms of changes in GMV in DM patients with cognitive impairment remain uncertain. Here, we present an overview of amyloid-ß-dependent cognitive impairment in DM patients with SCD. Moreover, we review the evolving insights from studies on the GMV changes in GMV and cognitive dysfunction to which provide the mechanisms of cognitive impairment in T2DM. Ultimately, the novel structural magnetic resonance imaging (MRI) protocol was used for detecting neuroimaging biomarkers that can predict the clinical outcomes in diabetic patients with SCD. A reliable MRI protocol would be helpful to detect neurobiomarkers, and to understand the pathological mechanisms of preclinical cognitive impairment in diabetic patients.

Cardiac autonomic neuropathy modified the association between obesity and hypoglycemia in type 2 diabetes.

BACKGROUND: Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this finding could be applied to patients with and without cardiac autonomic neuropathy (CAN). METHODS: The study included 7789 participants with type 2 diabetes from action to control cardiovascular risk in diabetes (ACCORD) trail. CAN was defined as SDNN < 8.2 ms and RMSSD < 8.0 ms. Obesity was defined as BMI ≥ 30 kg/m2. Outcomes were identified as severe hypoglycemia requiring any assistance (HAA) or requiring medical assistance (HMA). We assessed the association between obesity and severe hypoglycemia in type 2 diabetes with or without CAN using COX regression models adjusted for baseline characteristics. RESULTS: Over a median follow-up of 4.7 years, a total of 893 participants developed HAA and 584 participants developed HMA. Compared with non-obesity, obesity was associated with lower risk of severe hypoglycemia (HAA: hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.38-0.68, P < 0.001; HMA: HR 0.57, 95% CI 0.40-0.82, P = 0.002) in CAN present group, but not in CAN absent group (HAA: HR 0.98, 95% CI 0.83-1.16, P = 0.830; HMA: HR 0.97, 95% CI 0.79-1.19, P = 0.754). Similarly, increasing BMI was associated with reduced severe hypoglycemic events in participants with CAN, but not in participants without CAN. CONCLUSIONS: CAN modifies the association between obesity and hypoglycemia in type 2 diabetes. Type 2 diabetic individuals with CAN who are under weight control should pay attention to hypoglycemic events. TRIAL REGISTRY: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.

Mesoporous Silicon with Strontium-Powered Poly(Lactic-Co-Glycolic acid)/Gelatin-Based Dressings Facilitate Skin Tissue Repair.

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management. Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats. Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.). Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.

CT-based radiomics for predicting lymph node metastasis in esophageal cancer: a systematic review and meta-analysis.

Objective: We aimed to evaluate the diagnostic effectiveness of computed tomography (CT)-based radiomics for predicting lymph node metastasis (LNM) in patients diagnosed with esophageal cancer (EC). Methods: The present study conducted a comprehensive search by accessing the following databases: PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying relevant studies published until July 10th, 2023. The diagnostic accuracy was summarized using the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). The researchers utilized Spearman's correlation coefficient for assessing the threshold effect, besides performing meta-regression and subgroup analysis for the exploration of possible heterogeneity sources. The quality assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies-2 and the Radiomics Quality Score (RQS). Results: The meta-analysis included six studies conducted from 2018 to 2022, with 483 patients enrolled and LNM rates ranging from 27.2% to 59.4%. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC, along with their corresponding 95% CI, were 0.73 (0.67, 0.79), 0.76 (0.69, 0.83), 3.1 (2.3, 4.2), 0.35 (0.28, 0.44), 9 (6, 14), and 0.78 (0.74, 0.81), respectively. The results demonstrated the absence of significant heterogeneity in sensitivity, while significant heterogeneity was observed in specificity; no threshold effect was detected. The observed heterogeneity in the specificity was attributed to the sample size and CT-scan phases (P < 0.05). The included studies exhibited suboptimal quality, with RQS ranging from 14 to 16 out of 36. However, most of the enrolled studies exhibited a low-risk bias and minimal concerns relating to applicability. Conclusion: The present meta-analysis indicated that CT-based radiomics demonstrated a favorable diagnostic performance in predicting LNM in EC. Nevertheless, additional high-quality, large-scale, and multicenter trials are warranted to corroborate these findings. Systematic Review Registration: Open Science Framework platform at https://osf.io/5zcnd.

The gut microbe-derived metabolite trimethylamine-N-oxide induces aortic valve fibrosis via PERK/ATF-4 and IRE-1α/XBP-1s signaling in vitro and in vivo.

BACKGROUND AND AIMS: The gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) has been implicated in the development of cardiovascular fibrosis. Endoplasmic reticulum (ER) stress occurs after the dysfunction of ER and its structure. The three signals PERK/ATF-4, IRE-1α/XBP-1s and ATF6 are activated upon ER stress. Recent reports have suggested that the activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling contributes to cardiovascular fibrosis. However, whether TMAO mediates aortic valve fibrosis by activating PERK/ATF-4 and IRE-1α/XBP-1s signaling remains unclear. METHODS: Human aortic valve interstitial cells (AVICs) were isolated from aortic valve leaflets. PERK IRE-1α, ATF-4, XBP-1s and CHOP expression, and production of collagen Ⅰ and TGF-ß1 were analyzed following treatment with TMAO. The role of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in TMAO-induced fibrotic formation was determined using inhibitors and small interfering RNA. RESULTS: Diseased valves produced greater levels of ATF-4, XBP-1, collagen Ⅰ and TGF-ß1. Interestingly, diseased cells exhibited augmented PERK/ATF-4 and IRE-1α/XBP-1s activation after TMAO stimulation. Inhibition and silencing of PERK/ATF-4 and IRE-1α/XBP-1s each resulted in enhanced suppression of TMAO-induced fibrogenic activity in diseased cells. Mice treated with dietary choline supplementation had substantially increased TMAO levels and aortic valve fibrosis, which were reduced by 3,3-dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) treatment. Moreover, a high-choline and high-fat diet remodeled the gut microbiota in mice. CONCLUSIONS: TMAO promoted aortic valve fibrosis through activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in vitro and in vivo. Modulation of diet, gut microbiota, TMAO, PERK/ATF-4 and IRE1-α/XBP-1s may be a promising approach to prevent aortic valve fibrosis.

Intensive Glycemic Therapy in Type 2 Diabetes Patients With Cardiac Autonomic Dysfunction: The ACCORD Trial.

OBJECTIVE: To assess whether the presence of cardiac autonomic dysfunction denoted by low heart rate variability (HRV) modifies the effect of intensive glycemic therapy on outcomes in patients with type 2 diabetes. PATIENTS AND METHODS: This study included 7946 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial from January 2001 through June 2009. Heart rate variability measures included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Abnormal values were defined based on less than the 10th percentile for SDNN and rMSSD. RESULTS: Compared with standard therapy, intensive therapy was associated with improved primary outcome (composite of cardiovascular events) in the low-HRV group (SDNN: HR, 0.57; 95% CI, 0.39 to 0.84; rMSSD: HR, 0.57; 95% CI, 0.38 to 0.84), but not in the normal-HRV group (SDNN: HR, 0.90; 95% CI, 0.77 to 1.05; rMSSD: HR, 0.90; 95% CI, 0.77 to 1.05). A similar pattern was found for coronary heart disease. Conversely, intensive therapy had a neutral effect on all cause death in the low-HRV group (SDNN: HR, 0.88; 95% CI, 0.54 to 1.41; rMSSD: HR, 0.71; 95% CI, 0.43 to 1.17;), but increase risk of all-cause death in the normal-HRV group (SDNN: HR, 1.21; 95% CI, 1.00 to 1.46; rMSSD: HR, 1.25; 95% CI, 1.03 to 1.51). Intensive therapy induced a greater risk of hypoglycemia in the normal-HRV group than that in the low-HRV group. CONCLUSION: Cardiac autonomic dysfunction expressed as low HRV identified subpopulations in ACCORD with more benefits and less harms from intensive therapy.

Serum Klotho Modifies the Associations of 25-Hydroxy Vitamin D With All-Cause and Cardiovascular Mortality.

BACKGROUND: The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults. METHODS: A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality. RESULTS: We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P = .028). With klotho > 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho < 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D < 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI, .97-.99; HR, 0.98; 95% CI, .98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75). CONCLUSIONS: Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency.

Interplay of heart rate variability and resting heart rate on mortality in type 2 diabetes.

AIMS: Heart rate variability (HRV) and resting heart rate (RHR) are usually analyzed and interpreted separately. We aimed to assess the interplay of HRV and RHR on mortality in type 2 diabetes. METHODS: The study included 7,529 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. HRV metrics included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Abnormal values were defined based on <25th percentile for HRV and >75th percentile for RHR. Interactions of HRV status and RHR status were tested on multiplicative and additive scales. Results were validated in a subset of patients with type 2 diabetes (n = 745) from the Multi-Ethnic Study of Atherosclerosis. RESULTS: Low SDNN was associated with increased all-cause mortality in the high RHR group (HR 1.60; 95% CI 1.29-1.97), but not in the normal RHR group. Compared with those who had neither low SDNN nor high RHR, the presence of either low SDNN or high RHR was not significantly associated with an increased risk of all-cause mortality. In contrast, the combination of low SDNN and high RHR was associated with a significantly increased risk of all-cause mortality (HR 1.68; 95% CI 1.43-1.97). Significant multiplicative and additive interactions were found between HRV status and RHR status on risk of all-cause mortality (all Pinteraction < 0.05). Similar findings were observed for cardiovascular mortality, in analyses using rMSSD, and in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: The association between HRV and mortality risk is modified by RHR levels. Furthermore, low HRV and high RHR have interdependent and synergistic associations with mortality risk.

Non-invasive left ventricular myocardial work identifies subclinical myocardial involvement in patients with systemic lupus erythematosus.

OBJECTIVE: Global myocardial work (MW) is a novel indicator that accounts for deformation and afterload, which may provide additional value for assessment of myocardial function. Non-invasive echocardiographic estimated left ventricular (LV) MW incorporates longitudinal strain curves and blood pressure data. This study sought to assess MW in systemic lupus erythematosus (SLE) patients with normal LV ejection fraction (LVEF) by two-dimensional speckle-tracking imaging (2D-STI) to reflect subclinical myocardial damage. METHODS: 98 SLE patients and 98 gender and age-matched healthy subjects were included. The patients with SLE were divided into mild activity (SLE disease activity index (SLEDAI) ≤ 4; n = 45), moderate activity (5 ≤ SLEDAI ≤ 9; n = 23), and high activity (SLEDAI ≥ 10; n = 30) subgroups. Standard transthoracic echocardiography was applied to evaluate the systolic myocardial function of the global LV. The parameters of non-invasive MW including global wasted work (GWW) and global work efficiency (GWE) were calculated from echocardiographic LV pressure-strain loops (PSL) and blood pressure at rest. RESULTS: The SLE group had a significantly higher GWW (75.7 ± 39.1 mmHg% vs 37.9 ± 18.0 mmHg%, P < 0.001) and decreased GWE ratio (95.5 ± 2.0% vs 97.4 ± 1.0%, P < 0.001) compared with the controls. Among the subgroups with elevating level of disease activity, SLE patients with preserved LVEF had a significantly higher GWW (61.6 ± 29.9 mmHg% to 96.2 ± 42.2 mmHg%, P for trend = 0.001) and markedly decreased GWE (96.4 ± 1.5% to 94.4 ± 2.0%, P for trend = 0.001). In two separate multiple linear regression analyses, SLEDAI were independently associated with GWW (ß = 0.271, P = 0.005) and GWE (ß = -0.354, P<0.001). CONCLUSION: GWW and GWE are promising novel tools for the early detection of subclinical LV dysfunction. GWW and GWE could distinguish distinct patterns in different grades of SLEDAI.

Changes in Cardiovascular Health during Young Adulthood and Subclinical Atherosclerosis in Middle Age: The CARDIA Study.

Background and aims: The benefits of reaching ideal cardiovascular health (CVH) are well known, but it is unclear whether positive CVH changes from young adulthood to middle age reduce subclinical atherosclerosis risk. This study examined associations of changes in CVH from young adulthood to middle age and CVH in young adulthood with subclinical atherosclerosis. Methods: Data was analyzed from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CVH was examined at years 0 and 20 using Life Simple 7 metrics from AHA guideline. Coronary artery calcium (CAC) was identified at years 20 and 25. Carotid intima-media thickness (IMT) was identified at year 20. Results: Among 2,935 participants (56.2% women, 46.7% black), the change of CVH score was -1.26 (2.13). For per 1-unit increase in CVH at baseline, the adjusted odds ratios (ORs) of presence of CAC and IMT were 0.81 (95% CI 0.78, 0.86) and 0.85 (95% CI 0.76, 0.94), respectively. For per 1-unit increase in CVH changes, the adjusted ORs of CAC and IMT were 0.86 (95% CI 0.82, 0.90) and 0.81 (95% CI 0.73, 0.90). Compared with stable moderate CVH, improvement from moderate to high was associated with a lower risk of CAC (0.64 [95% CI 0.43, 0.96]), while retrogression from moderate to low was associated with a higher risk of CAC (1.45 [95% CI 1.19, 1.76]). Conclusions: Positive changes of CVH during young adulthood are associated with negative subclinical atherosclerosis risk in middle age, indicating the importance of reaching an ideal cardiovascular health status through young adulthood.

Body weight time in target range and cardiovascular outcomes in adults with overweight/obesity and type 2 diabetes.

AIMS: Prescription of weight loss to individuals is often characterized by weight fluctuations. However, current body weight management metrics may have difficulty characterizing the changes in body weight over time. We aim to characterize the long-term changes using body weight time in target range (TTR) and test its independent association with cardiovascular outcomes. METHODS AND RESULTS: We included 4468 adults from the Look AHEAD (Action for Health in Diabetes) trial. Body weight TTR was defined as the percentage of time during which body weight was within the Look AHEAD weight loss goal range. The associations of body weight TTR with cardiovascular outcomes were analysed using multivariable Cox modelling and restricted cubic spline function. Among the participants (mean age 58.9 years, 58.5% women, 66.5% White), there were 721 incident primary outcomes [cumulative incidence: 17.5%, 95% confidence interval (CI): 16.3-18.8%] during a median of 9.5 years of follow-up. Each 1 SD increase in body weight TTR was significantly associated with a decreased risk of the primary outcome (hazard ratio: 0.84, 95% CI: 0.75-0.94) after adjusting for mean and variability of body weight and traditional cardiovascular risk factors. Further analyses using restricted cubic spline indicated the inverse association between body weight TTR and the primary outcome in a dose-dependent manner. Similar associations remained significant among the participants with lower baseline or mean body weight. CONCLUSION: In adults with overweight/obesity and type 2 diabetes, higher body weight TTR was independently associated with lower risks of cardiovascular adverse events in a dose-response manner.

We used time in target range (TTR) to characterize the long-term changes in body weight among 4468 adults with overweight/obesity and type 2 diabetes and assessed the associations of body weight TTR with cardiovascular outcomes.Participants with TTR of >50­100% achieved and maintained the target of body weight loss during the 10 years of follow-up.Higher body weight TTR was independently associated with lower risks of cardiovascular adverse events in a dose­response manner.

Triglyceride-glucose index in the development of heart failure and left ventricular dysfunction: analysis of the ARIC study.

AIMS: We aimed to investigate whether the triglyceride-glucose (TyG) index, an easy-calculated and reliable surrogate of insulin resistance, was associated with the development of heart failure (HF) and left ventricular (LV) dysfunction. METHODS AND RESULTS: A total of 12 374 participants (mean age: 54.1 ± 5.7 years, male: 44.7%) free of history of HF and coronary heart disease at baseline from the Atherosclerosis Risk in Communities study were included. The TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The long-term TyG index was calculated as the updated cumulative average TyG index using all available TyG index from baseline to the events of HF or the end of follow-up. We evaluated the associations of both the baseline and the long-term TyG index with incident HF using Cox regression analysis. We also analysed the effect of the TyG index on LV structure and function among 4889 participants with echocardiographic data using multivariable linear regression analysis. There were 1958 incident HF cases over a median follow-up of 22.5 years. After adjusting for potential confounders, 1-SD (0.60) increase in the baseline TyG index was associated with a 15% higher risk of HF development [hazard ratio (HR): 1.15, 95% confidence interval (CI): 1.10-1.21]. Compared with participants in the lowest quartile of the baseline TyG index, those in the highest quartile had a greater risk of incident HF [HR (95% CI): 1.25 (1.08-1.45)]. In terms of LV structure and function, a greater baseline TyG index was associated with adverse LV remodelling and LV dysfunction. Similar results were found for the long-term TyG index. CONCLUSION: In a community-based cohort, we found that a greater TyG index was significantly associated with a higher risk of incident HF and impaired LV structure and function.

Intensity of hypertensive exposure in young adulthood and subclinical atherosclerosis in middle age: Evidence from the CARDIA study.

Background: Chronically high blood pressure (HBP) is a known risk factor for cardiovascular diseases. We measured the intensity of hypertensive exposure in young adults and calculated its prognostic significance for subclinical atherosclerosis in middle age. Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled 5,115 healthy black and white Americans who were 18-30 years old at baseline (1985-1986). The intensity of hypertensive exposure was calculated as the area under the curve (mm Hg × years) from baseline to year 15. Coronary artery calcium (CAC) was identified at years 15, 20, and 25, and intima-media thickness (IMT) was identified at year 20. Results: At baseline, the mean age was 40.1 years; 55.1% of participants were women, and 46.5% were black. After adjustment, cumulative systolic BP (SBP) was positively associated with CAC [hazard ratio (HR) = 1.23 (1.14, 1.32)] and IMT [ß = 0.022 (0.017, 0.028)]. For CAC, the C-statistic for cumulative SBP was 0.643 (0.619, 0.667); compared to baseline SBP, the net reclassification index (NRI) of cumulative SBP was 0.180 (0.115, 0.256) and the integrated discrimination improvement (IDI) was 0.023 (0.012, 0.036). For IMT, the C-statistic for cumulative SBP was 0.674 (0.643, 0.705), the NRI was 0.220 (0.138, 0.305), and the IDI was 0.008 (0.004, 0.0012). Conclusion: Greater intensity of hypertensive exposure in early adulthood is associated with subclinical atherosclerosis in middle age and provides better prognostic value than baseline BP for early cardiovascular risk.

Lacunes and type 2 diabetes mellitus have a joint effect on cognitive impairment: a retrospective study.

Objective: To evaluate the joint effects of cerebral small vessel disease (CSVD)-related imaging biomarkers in patients of type 2 diabetes mellitus (T2DM) with cognitive impairment. Methods: This study is a retrospective cohort study. A total of 227 participants (115 patients with T2DM and 112 healthy control subjects) were enrolled in this study. Cognitive function assessments were evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. The burden of CSVD markers, including the lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), and enlarged perivascular spaces (PVS), was identified by magnetic resonance imaging and evaluated using small vessel disease (SVD) scores (0-4). The subjects were divided into two groups based on the results of the cognitive function assessments. The synergy index was used to estimate the biological interactions between T2DM and lacunes. Results: There was a significant correlation between T2DM and cognitive impairment (p < 0.001, χ2 test). In patients with diabetes, cognitive impairment was significantly associated with both the presence of lacunes (p < 0.01, χ2 test) and increased total SVD burden scores (p < 0.01, χ2 test). Regarding CMBs, only the existence of lobar CMBs was correlated with cognitive impairment (p < 0.05, χ2 test). The joint effect tended to be larger than the independent effects of T2DM and lacunes on cognitive impairment (adjusted odds ratio [OR]: 7.084, 95% CI [2.836-17.698]; synergy index: 10.018, 95% CI [0.344-291.414]). Conclusions: T2DM and the presence of lacunes are significantly correlated with cognitive impairment. There was a joint effect of T2DM and lacunes on cognitive impairment.

Visit-to-Visit Fasting Glucose Variability in Young Adulthood and Cardiac Structure and Function at Midlife: The CARDIA Study.

Glycemic variability was found associated with left ventricular structure and function in type 2 diabetes. But it is still unclear that whether the greater visit-to-visit fasting glucose (FG) variability in young adulthood among the community population is associated with cardiac function alteration and cardiac remodeling at midlife. The community-based prospective cohort study of Coronary Artery Risk in Young Adult (CARDIA) recruited young participants at the baseline age of 18-30 years during the period of 1985-1986 (Year 0). FG was measured at Year 0, 2, 10, 15, 20, and 25. The echocardiographic evaluation of cardiac structure and function was conducted at year 25. A total of 2,600 young adults mean (SD) aged at 24.9 years (3.6) of which 57.3% were women and 46.7% were African Americans had been included in the study. After multivariable adjusted, higher SD of mean FG (SDFG) is associated with lower early peak diastolic septal mitral annular velocity (e') (ß [SE], -0.214 [0.080], P < 0.01) and higher E/e' (ß [SE], 0.307 [0.094], P < 0.01), and higher coefficient of variation of the mean FG (CVFG) is also associated with lower e' (ß [SE], -0.141[0.066], P < 0.05) and higher E/e' (ß [SE], 0.204 [0.078], P < 0.01). The higher average real variation of mean FG (ARVFG) is associated with higher E/e' (ß [SE], 0.178 [0.085], P < 0.05) and higher left ventricular mass index (LVMI) (ß [SE], 1.240 [0.618], P < 0.05). The higher FG variability in young adulthood is associated with the subclinical change of left ventricular (LV) diastolic function at midlife.

Antiplatelet strategy in primary and secondary prevention of cardiovascular disease in patients with type 2 diabetes mellitus: A perspective from the guideline appraisal.

AIMS/INTRODUCTION: To appraise guidelines on the antiplatelet strategy of prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus, and highlight the consensuses and controversies to aid clinician decision-making. MATERIALS AND METHODS: A systematic search was carried out for guidelines regarding CVD prevention or focusing on type 2 diabetes patients. Appraisal of Guidelines for Research and Evaluation II instrument was utilized to appraise the quality of included guidelines. RESULTS: Of the 15 guidelines with discrepant Appraisal of Guidelines for Research and Evaluation II scores (66%; interquartile range 51-71%), 10 were defined as "strongly recommended" guidelines. For secondary prevention, >60% of guidelines advocated that the dual antiplatelet therapy was used within 12 months when the type 2 diabetes patients experienced acute coronary syndrome and/or post-percutaneous coronary intervention or coronary artery bypass grafting, with subsequent long-term aspirin use. For primary prevention, 80% of guidelines supported that aspirin should not be routinely used by patients with type 2 diabetes. No consensus on whether to prolong dual antiplatelet therapy in secondary prevention, and whether to use aspirin in type 2 diabetes patients with high CVD risk exists in current guidelines. CONCLUSIONS: Physicians should use the recommendations from "strongly recommended" guidelines to make informed decisions and know the consensuses of current guidelines. Dual antiplatelet therapy should be used within 12 months when type 2 diabetes patients experience acute coronary syndrome and/or percutaneous coronary intervention/coronary artery bypass grafting, with subsequent long-term aspirin use. In primary prevention, aspirin should not be routinely used by individuals with type 2 diabetes, but might be considered for those with high CVD risk.

Cerebral microbleeds, cognitive impairment, and MRI in patients with diabetes mellitus.

Cerebral microbleeds (CMBs), a typical imaging manifestation marker of sporadic cerebral small vessel disease, play a critical role in vascular cognitive impairment, which is often accompanied by diabetes mellitus (DM). Hence, CMBs may, in part, be responsible for the occurrence and development of cognitive impairment in patients with diabetes. Novel magnetic resonance imaging (MRI) sequences, such as susceptibility-weighted imaging and T2*-weighted gradient-echo, have the capability of noninvasively revealing CMBs in the brain. Moreover, a correlation between CMBs and cognitive impairment in patients with diabetes has been suggested in applications of functional MRI (fMRI). Since pathological changes in the brain occur prior to observable decline in cognitive function, neuroimaging may help predict the progression of cognitive impairment in diabetic patients. In this article, we review the detection of CMBs using MRI in diabetic patients exhibiting cognitive impairment. Future studies should emphasize the development and establishment of a novel MRI protocol, including fMRI, for diabetic patients with cognitive impairment to detect CMBs. A reliable MRI protocol would also be helpful in understanding the pathological mechanisms of cognitive impairment in this important patient population.