Serum uric acid as a risk factor of all-cause mortality and cardiovascular events among type 2 diabetes population: Meta-analysis of correlational evidence

AimsTo explore the association between serum uric acid (SUA) level and the risk of cardiovascular complications and all-cause mortality rates among individuals with type 2 diabetes.MethodsWeb of Science and PubMed database were searched for studies reported associations between SUA level and cardiovascular complications and all-cause mortality among individuals with type 2 diabetes. Hazard ratios (HRs) were independently extracted by two investigators and synthesized through meta-analysis across selected studies.Results6 (n = 11,750 patients), 4 (n = 3044 patients) and 2 studies (n = 7792 patients) were identified reporting associations between SUA level and all-cause mortality, coronary heart disease (CHD) and stroke respectively. HR for all-cause mortality, CHD, and stroke per 59 μmol/l increase was 1.06 (95% CI: 1.03, 1.09), 1.09 (95% CI: 0.94, 1.26) and 1.19 (95% CI: 1.08, 1.31), respectively.ConclusionsOverall, the SUA level was associated with a higher risk of all-cause mortality and stroke. We found no significant association between SUA level and CHD among type 2 diabetes population.     

Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study

Background and aimsFew studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population.Methods and resultsParticipants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729–3.884), male subjects (HR: 2.903 and 95% CI: 1.718–4.906), and female subjects (HR: 2.081 and 95% CI: 1.071–4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60–69 and 70–79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444–5.678 and 1.394–4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality.ConclusionsSevere malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.     

Comparative efficacy,safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1–7 trials

In individuals with type 2 diabetes, glycaemic control and cardiovascular risk factor management reduces the likelihood of late-stage diabetic complications. Guidelines recommend treatment goals targeting HbA_1c, body weight, blood pressure, and low-density lipoprotein cholesterol. Development of new treatments for type 2 diabetes requires an understanding of their mechanism and efficacy, as well as their relative effects compared to other treatment choices, plus demonstration of cardiovascular safety. Subcutaneous semaglutide is a glucagon-like peptide-1 receptor agonist currently approved in several countries for once-weekly treatment of type 2 diabetes. Semaglutide works via the incretin pathway, stimulating insulin and inhibiting glucagon secretion from the pancreatic islets, leading to lower blood glucose levels. Semaglutide also decreases energy intake by reducing appetite and food cravings, and lowering relative preference for fatty, energy-dense foods. Semaglutide was evaluated in the SUSTAIN clinical trial programme in over 8000 patients across the spectrum of type 2 diabetes. This review details the efficacy and safety profile of semaglutide in the SUSTAIN 1–5 and 7 trials, and its cardiovascular safety profile in the SUSTAIN 6 trial. Semaglutide consistently demonstrated superior and sustained glycemic control and weight loss vs. all comparators evaluated. In SUSTAIN 6, involving patients at high risk of cardiovascular disease, semaglutide significantly decreased the occurrence of cardiovascular events compared with placebo/standard of care (hazard ratio 0.74, P < 0.001 for non-inferiority). Through a comprehensive phase 3 clinical trial program, we have a detailed understanding of semaglutide’s efficacy, safety, cardiovascular effects and comparative role in the treatment of type 2 diabetes.     

Impact of Lipoprotein(a) concentrations on long-term cardiovascular outcomes in patients undergoing percutaneous coronary intervention: A large cohort study

Background and aimsTill now, the prognostic value of lipoprotein(a) [Lp(a)] in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) remains controversial. We therefore conducted this study to evaluate the effect of Lp(a) levels on clinical outcomes in this population.Methods and resultsA total of 10,059 CAD patients who underwent PCI were prospectively enrolled in this cohort study, of which 6564 patients had Lp(a) ≤30 mg/dl and 3495 patients had Lp(a) > 30 mg/dl. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, stroke or unplanned revascularization. Multivariate Cox regression analysis and propensity-score matching analysis were performed. After propensity-score matching, 3449 pairs of patients were identified, and post-matching absolute standardized differences were <10% for all the covariates. At 2.4 years, the risk of MACCE was significantly higher in patients with elevated Lp(a) levels than those with normal Lp(a) levels in both overall population (13.0% vs. 11.4%; adjusted hazard ratio [HR] 1.142, 95% confidence interval [CI] 1.009–1.293; P = 0.040) and propensity-matched cohorts (13.0% vs. 11.2%; HR 1.167, 95%CI 1.019–1.337; P = 0.026). Of note, the predictive value of Lp(a) levels on MACCE tended to be more evident in individuals >65 years or those with left main and/or three-vessel disease. On the contrary, elevated Lp(a) levels had almost no effect on clinical outcomes in patients ≤65 years (P _interaction = 0.021) as well as those who had one- or two-vessel coronary artery disease (P _interaction = 0.086).ConclusionIn CAD patients who underwent PCI, elevated Lp(a) levels were positively related to higher risk of MACCE at 2.4-year follow-up, especially in patients >65 years and those with left main and/or three-vessel disease.Registration numbernot applicable.     

Mechanisms of Myocardial Ischemia Inducing Sudden Cardiac Death in Athletes with Anomalous Coronary Origin from the Opposite Sinus: Insights from a computational fluid dynamic study

AimsThe left coronary anomalous origin from the opposite sinus (L- ACAOS) constitutes the most clinically relevant arterial abnormality among the wide spectrum of coronary artery anomalies. We investigated the physiology of L-ACAOS with and without intramural course (IM) in athletes, using the computational fluid dynamic (CFD) analysis.Methods and resultsThe coronary artery circulation with L-ACAOS with and without IM has been segmented and then reconstructed, after reviewing both the angiographic and computed tomography findings of 13 consecutive athletes (10 males, mean age 45.1 ± 8.2 years) with L-ACAOS collected in our institution between 1st January 2003 and 1st January 2018. Vorticity magnitude, static pressure and wall shear stress (WSS) have been analysed in a model of L-ACAOS with no IM course and in L-ACAOS-IM at rest and during exercise. The mean vorticity magnitude and WSS significantly increased from rest to exercise in both models, in right coronary artery, left anterior descending and left circumflex coronary arteries. The mean static pressure significantly increased with exercise in IM (1.118e + 004 vs 1.164e + 004 Pa, p < 0.001) as well as the mean vorticity magnitude and the mean WSS (7012.78 1/s vs 9019.56 1/s, p < 0.001, Δ = 2006.78 1/s and 3.02 Pa vs 2.11 Pa, p < 0.001, Δ = 0.91 Pa). This net increment was transmitted to the entire left coronary system in L-ACAOS-IM but not in L-ACAOS with no IM.ConclusionsIn L-ACAOS, different hemodynamic parameters observed in the intramural segment seem to confirm that IM is compressed during exercise. These rheological properties might propagated along the left coronary system, potentially predisposing, if confirmed in vivo, distal coronary segments to a higher risk of spasm and thrombosis in athletes.     

HDL3-C is a Marker of Coronary Artery Disease Severity and Inflammation in Patients on Statin Therapy

IntroductionLow high-density lipoprotein (HDL-C) and inflammation are risk factors for coronary artery disease (CAD). However, limited data are available determining the role of HDL-C sub-particles HDL₂-C and HDL₃-C for assessing CAD severity in patients on statin therapy.MethodsBlood samples were obtained prior to cardiac catheterization in 304 consecutive patients with suspected CAD on statin therapy in this sub-analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Detailed lipid profiling and oxidized LDL (ox-LDL) were analyzed. CAD severity was angiographically defined as severe CAD (>75% luminal diameter stenosis [LDS]) and non-severe CAD (≤75% LDS). Multi-regression analysis was performed to test for statistical significance. Receiver operator curve (ROC) analysis was performed to determine cut-point for predicting severe CAD.ResultsPatients with severe CAD had a significantly lower total-HDL-C, lower HDL₃-C and higher lipoprotein(a) levels. HDL₃-C and lipoprotein(a) cholesterol [Lp(a)-C] retained statistical significance on multiple regression analysis. ROC analysis showed HDL₃-C to have a C-statistic of 0.60 (p = 0.003) and Lp(a)-C to have a C-statistic of 0.61 (p = 0.0007). Patients with HDL₃-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL were found to have significantly elevated ox-LDL levels.ConclusionIn patients on statin therapy, HDL₃-C and Lp(a)-C improve prediction of severe CAD compared to a traditional lipid panel. In addition, patients with HDL₃-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL have greater inflammation marked by ox-LDL. Further studies are needed to evaluate the utility of these novel biomarkers in predicting CAD severity.     

Urban/rural residence effect on emergency department visits arising from food-induced anaphylaxis

BackgroundAnaphylaxis is a severe and potentially fatal allergic response. Early-life exposure to rural environments may help protect against allergic reaction. This study assesses urban/rural differences by age and race/ethnicity in emergency department (ED) pediatric visit rates for food-induced anaphylaxis.MethodsThis observational study examined 2009–2014 inpatient and ED data from New York and Florida, using ICD-9-CM diagnostic code (995.6) to identify food-induced anaphylaxis cases <18 y/o. Primary predictor of interest was urban/rural setting, with race/ethnicity and age also evaluated. Associations between ED visit rates and urban/rural setting were evaluated by multivariable hierarchical negative binomial regression with state and year fixed effects.ResultsED visit rates (per 100,000) for food-induced anaphylaxis were 12.31 and 4.60 in urban and rural settings, respectively. Rates were highest among Blacks (15.26) younger urban children (17.29) and older rural children (6.99). Compared to rural, urban children had significantly higher anaphalaxis ED visit rates (IRR 2.77).ConclusionsFood-induced anaphylaxis ED visit rates were highest among younger urban children and Black children, with a notable contrast in age distribution between urban and rural rates. Higher urban rates may be attributed to Hygiene Hypothesis, though racial, economic and emergency care access disparities may also influence these outcomes.     

Relationship between serum levels of immunoglobulins and metabolic syndrome in an adult population: A population study from the TCLSIH cohort study

Background and aimsMetabolic syndrome (MetS) is a combination of metabolic disorders that increase the risk of developing cardiovascular disease, and inflammation is considered as a pathological basis for MetS. Immunoglobulins (Igs) are the major secretory products of the adaptive immune system. However, no large-scale population study has focused on a possible relationship between Igs and MetS. We designed a cross-sectional study to investigate the relationship between Igs and prevalence of MetS in a large-scale adult population.Methods and resultsA total of 10,289 participants were recruited among residents in Tianjin, China. Metabolic syndrome was defined in accordance with the criteria of the American Heart Association scientific statements of 2009. Serum levels of Igs were determined by immunonephelometry. Multiple logistic regression models were used to assess the relationship between the quintiles of serum levels of Igs and the prevalence of MetS. The overall prevalence of MetS was 36.1%. The mean (standard deviation) values of Igs (IgG, IgE, IgM, and IgA) were 1205.7 (249.3) mg/dL, 93.1 (238.9) IU/mL, 105.7 (57.3) mg/dL, and 236.2 (97.6) mg/dL, respectively. The adjusted odds ratios (95% confidence interval) of MetS for the highest quintile of Igs (IgG, IgE, IgM, and IgA), when compared to the lowest quintile, were 0.81 (0.70, 0.95), 0.97 (0.83, 1.12), 1.13 (0.97, 1.33), and 1.52 (1.30, 1.77), respectively.ConclusionsThis study demonstrated that decreased IgG and increased IgA are independently related to a higher prevalence of MetS. The results indicate that the Igs might be useful predictive factors for MetS in the general adult population.     

Association of Life's Essential 8 with all-cause and cardiovascular mortality among US adults: A prospective cohort study from the NHANES 2005–2014

Background and aimsThis study aims to investigate the association of Life's Essential 8 (LE8), the recently updated algorithm for quantifying cardiovascular health (CVH) by the American Heart Association (AHA), with long-term outcomes among US adults.Methods and resultsThis population-based prospective cohort study analyzed data of 23,110 participants aged 20 years or older from the National Health and Nutrition Examination Survey from 2005 to 2014 and their linked mortality data through December 2019. LE8 score (range 0–100) was measured according to AHA definitions and was categorized into low (0–49), moderate (50–79), and high (80–100) CVH. The weighted mean age of the study population was 47.0 years (95% confidence interval [CI], 46.4–47.5 years), and 11,840 were female (weighted percentage, 51.5%; 95% CI, 50.9–52.1%). During a median follow-up period of 113 months (up to 180 months), 2942 all-cause deaths occurred, including 738 CVD deaths. The LE8 score was significantly and inversely related to mortality from all causes (adjusted hazard ratio [HR] for per 10-score increase in LE8 score, 0.86; 95% CI, 0.82–0.90) and cardiovascular disease (adjusted HR for per 10-score increase in LE8 score, 0.81; 95% CI, 0.75–0.87). Compared with participants having low CVH, those having high CVH had a reduction of 40% (adjusted HR, 0.60; 95% CI, 0.48–0.75) in the risk for all-cause mortality and 54% (adjusted HR, 0.46; 95% CI, 0.31–0.68) in the risk for cardiovascular mortality.ConclusionsHigher LE8 score was independently associated with lower risks of all-cause and cardiovascular mortality among US adults.     

Incremental risk of cardiovascular disease and/or chronic kidney disease for future ASCVD and mortality in patients with type 2 diabetes mellitus: ACCORD trial

BackgroundCardiovascular disease (CVD) and chronic kidney disease (CKD) are complications of type 2 diabetes mellitus (DM). Current cholesterol guidelines recommend the same prevention strategy for patients with DM alone as patients with DM + CKD. However, the incremental risk of these common complications for incident cardiovascular disease and mortality has not been well studied.MethodsWe compared the incremental risk of having DM + CKD, DM + CVD and DM + CVD + CKD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants for incident CVD as the primary outcome and all-cause mortality.ResultsAfter a mean (SD) follow up of 4.7(1.4) years, 1,046(10%) participants developed CVD. DM +vCKD, DM + CVD, and DM + CKD + CVD had a significantly increased risk of the primary outcome compared to DM alone [adjusted hazard ratio(95%CI): 1.41 (1.06-1.89), p = 0.02; 2.20 (1.92-2.53), p < 0.001); 2.35 (1.81-3.04), p < 0.001), respectively]. All-cause mortality had a graded increased risk compared to the reference group [adjusted hazard ratio(95%CI): 1.39 (1.01-1.90), p = 0.04; 1.29 (1.51-2.12), p < 0.0001; 2.36 (1.75-3.13), p < 0.0001), respectively].ConclusionOur post hoc analysis shows an incremental graded risk for CVD outcomes and all-cause mortality with the development of CKD and/or CVD in individuals with DM.     

Analysis of the duration and extent of the legacy effect in patients with type 2 diabetes: A real-world longitudinal study

AimsTo analyze the duration and extent of the legacy effect on diabetic complications in real-world patients with type 2 diabetes.MethodsThis was a retrospective cohort study. We included the following three cohorts of patients: diabetic retinopathy (DR) (n = 1107), diabetic kidney disease (DKD) (n = 1486), and cardiovascular disease (CVD) (n = 1485). Patients were enrolled from 1995 to 1999 and followed up to 2017. Endpoints were DR incidence, ≥40% decrease in estimated glomerular filtration rate, and CVD incidence. The relationships between HbA1c as a time-dependent variable and the risk of reaching each endpoint were analyzed using multivariate Cox regression models.ResultsA total of 313 patients developed DR, 316 developed DKD, and 177 developed CVD. Hazard ratios as a function of time-dependent HbA1c (moving mean) accumulated over time. This accumulation was largest for DR, followed by DKD and CVD. The hazard ratios for each endpoint reached a plateau during the preceding 14–19 years.ConclusionsThe effect of past glycemic control may continue during 14–19 years, with a greater effect during ≤10 years. Therefore, the end of the legacy effect could be 15–20 years. This effect may be the greatest for DR, followed by DKD, and the smallest for CVD.     

Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study

BackgroundNovel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM).MethodsA prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up.Main findingsThe composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38–6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40– 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers.ConclusionsPatients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.     

Bone mineral density in patients with longstanding type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

AimIt is currently unclear if longstanding type 1 diabetes (T1D) affects bone mineral density (BMD).MethodsBMD measured by dual-energy X-ray absorptiometry and history of fragility fracture was determined in 75 T1D participants with ≥50 years of diabetes duration and 75 age- and sex-matched non-diabetic controls. BMD T-scores were determined for the lumbar spine (LS), total hip (TH) and femoral neck (FN).ResultsT1D participants had median diabetes duration of 54 [52, 58] years, 41 (55%) were females, and mean A_1c was 7.3 ± 0.8%. T1D females had higher LS T-scores compared to female controls (?0.3 ± 1.2 vs. ?1.1 ± 1.4, p = 0.014), lower FN T-scores (?1.5 ± 1.0 vs. ?1.2 ± 0.9, p = 0.042) and more fragility fractures (7 (17%) vs. 1 (2%), p = 0.021). In T1D, higher A1c was associated with higher adjusted odds of fragility fracture (p = 0.006). T1D males and controls showed no difference in BMD or fractures.ConclusionsThere were no substantial differences in T-score between T1D and matched controls; however, T1D females showed higher BMD at the LS and possibly paradoxically higher fragility fractures compared to matched controls. These findings suggest that lower T-scores may not be associated with a history of fragility fracture in females with longstanding T1D and that other factors should be investigated.     

Epicardial adipose tissue volume as a marker of coronary artery disease severity in patients with diabetes independent of coronary artery calcium: Findings from the CTRAD study

AimsThe association between epicardial adipose tissue (EAT) volume and coronary artery disease (CAD) severity was evaluated, independent of traditional risk factors and coronary artery calcium (CAC) scores, in patients with diabetes type 2 (DM-2) using cardiac computed tomography angiography (CTA).MethodsA multivariate analysis was utilized to assess for an independent association after calculating EAT volume, CAD severity, and calcium scores in 92 patients with DM-II from the CTRAD study. We graded CAD severity as none (normal coronaries), mild-moderate (<70% stenosis), and severe (70% or greater stenosis).ResultsA total of 39 (42.3%) asymptomatic patients with diabetes did not have CAD; 30.4% had mild/moderate CAD; and 27.1% had severe CAD. Mean EAT volume was highest in patients with severe CAD (143.14 cm³) as compared to mild/moderate CAD (112.7 cm³), and no CAD (107.5 cm³) (p = 0.003). After adjustment of clinical risk factors, notably, CAC score, multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample (odds ratio 11.2, 95% confidence interval 1.7–73.8, p = 0.01).ConclusionsIncreasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD, independent of BMI and CAC, as well as traditional risk factors.     

Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study

Background and aimsCoronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD.Methods and resultsThis was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131–3.136]), C-reactive protein (1.046 [1.020–1.073]), blood pressure >140/90 mmHg (2.686 [1.506–4.791]), fibrates (2.032 [1.160–3.562]), calcium channel blockers (2.082 [1.158–3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240–4.721]), heart failure (2.139 [1.032–4.433]), LDL-C >70 mg/dL (4.594 [1.401–15.069]), and diuretics (3.328 [1.677–6.605]) were associated with cardiovascular mortality.ConclusionsThe composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.     

Lipoprotein(a): An underrecognized genetic risk factor for malignant coronary artery disease in young Indians

Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged <45 years in men and <50 years in women) with a low or no burden of established risk factors. Indians, in general, develop acute myocardial infarction (AMI) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations. Although established CAD risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians. Lipoprotein(a) (Lp(a)) is increasingly recognized as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD. High Lp(a) levels confer a twofold to threefold risk of CAD—a risk similar to that of established risk factors, including diabetes. South Asians have the second highest Lp(a) levels and the highest risk of AMI from the elevated levels, more than double the risk observed in people of European descent. Approximately 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance, similar to or surpassing diabetes. Lp(a) measurement is ready for clinical use and should be an essential part of all CAD research in Indians.