Sex differences in cardiovascular risk factors of children and adolescents with type 1 diabetes mellitus: A role for diet?

Background and aimsCardiovascular disease is the leading cause of morbidity and mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk is higher in women with diabetes than in men. With this study, we wanted to determine whether female children and adolescents with T1DM are more prone to cardiovascular risk factors (CVRFs) and an atherogenic diet than boys.Methods and resultsFor this cross-sectional study, anthropometric, clinical, biochemical, and dietary intake data of 314 children with diabetes (3–18 years; 178 boys) were analysed according to age and sex. Linear and binary logistic regression was performed to test independent associations between sex, dietary intake, and CVRFs.Low-density lipoprotein -cholesterol (LDL-c), triglyceride (TG), fibre, monounsaturated fatty acid levels (all p < 0.01), and lipid (p = 0.022) intake were higher in the girls than in the boys. Multiple regression analysis showed that LDL was associated with sex, glycated haemoglobin (HbA1c), and lipid intake percentage (R (Kannel, 1979) [2] = 0.130; p = 0.0004) independent of age, pubertal stage, body mass index (BMI), duration of diabetes, energy, and fibre intake. Logistic regression analysis showed that high LDL-c levels were present more often in girls [odds ratio, OR; confidence interval, CI = 2.569 (1.178–5.604); p = 0.018] who had a higher dietary lipid intake percentage [OR (CI) = 1.089 (1.011–1.173); p = 0.025].ConclusionsGirls with diabetes have higher LDL-c levels associated with higher dietary lipid intake. Our findings suggest that young people with diabetes, especially girls, may benefit from early dietary interventions to reduce their cardiovascular risk.     

Subclinical Atherosclerosis and Brain Metabolism in Middle-Aged Individuals: The PESA Study

BackgroundAtherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored.ObjectivesThis study sought to determine the association between brain metabolism, subclinical atherosclerosis, and CVRFs in middle-aged asymptomatic individuals.MethodsThis study included 547 asymptomatic middle-aged participants (50 ± 4 years, 82% men) from the PESA (Progression of Early Subclinical Atherosclerosis) study with evidence of subclinical atherosclerosis. Participants underwent ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography. Global brain FDG uptake and voxel-wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3-dimensional vascular ultrasound.ResultsGlobal FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (FRS) (β = ?0.15, p < 0.001). This association was mainly driven by the presence of hypertension (d = 0.36, p < 0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β = ?0.16, p < 0.001), even after adjusting for 30-year FRS. Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30-year FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus.ConclusionsIn asymptomatic middle-aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism include those known to be affected in dementia. These data reinforce the need to control CVRFs early in life in order to potentially reduce the brain’s midlife vulnerability to future cognitive dysfunction.     

The role of the plasma glycosylated hemoglobin A1c/Apolipoprotein A-l ratio in predicting cardiovascular outcomes in acute coronary syndrome

Background and aimsGlucose and lipid metabolism are major prognostic indicators of coronary heart disease. The ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-l (ApoA-l) is an indirect measure of insulin resistance. The study aimed to evaluate whether the HbA1c/ApoA-1 ratio can predict the prognosis in patients with the acute coronary syndrome (ACS).Methods and resultsA total of 476 ACS patients diagnosed by coronary angiography were enrolled in this longitudinal, observational, retrospective study. Plasma HbA1c, fasting blood glucose and lipid profile were measured. Patients were stratified according to the tertiles of HbA1c/ApoA-l levels. Cox proportional hazard model was used to examine the predictive value of HbA1c/ApoA-l for study endpoints. The association between the Log HbA1c/ApoA-l ratio and major adverse cardiovascular events (MACEs) was estimated using multiple logistic regression. Baseline characteristics showed a mean age of 66 ± 8 years, and 52.5% were hypertensive, 26.8% diabetic, and 54.5% current or prior smokers. During a mean follow-up period of 22.3 ± 1.7 months, 59 deaths occurred. After adjusting for age, gender, smoking, hypertension, diabetes, and coronary artery disease severity, patients in the highest HbA1c/ApoA-l ratio tertile had a 4.36-fold increased risk of mortality compared with those in the lowest tertile. The multivariate logistic regression showed that the Log HbA1c/ApoA-l ratio was associated with MACEs (Odds ratio 2.95, p = 0.013).ConclusionAfter adjusting for traditional cardiovascular risk factors and ACS severity scores, the HbA1c/ApoA-1 ratio remained an independent predictor of all-cause mortality and MACEs in the ACS patients undergoing angiography.     

Efficacy and safety of PCSK9 inhibitors in patients with diabetes: A systematic review and meta-analysis

AimsIndividuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects for diabetic patients. We conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors for diabetes.Data synthesisWe performed a meta-analysis comparing treatment with PCSK9 inhibitors versus controls up to July 2022. Primary efficacy endpoints were percentage changes in lipid profile parameters. We used random effects meta-analyses to combine data. Subgroups of diabetic patients (by diabetes type, baseline LDL-C, baseline HbA1c and follow-up time) were also compared. We included 12 RCTs comprising 14,702 patients. Mean reductions in LDL-C were 48.20% (95% CI: 35.23%, 61.17%) in patients with diabetes. Reductions observed with PCSK9 inhibitors were 45.23% (95% CI: 39.43%, 51.02%) for non-HDL-cholesterol, 30.39% (95% CI: 24.61%, 36.17%) for total cholesterol, 11.96% (95% CI: 6.73%, 17.19%) for triglycerides, 27.87% (95% CI: 22.500%, 33.17%) for lipoprotein(a), 42.43% (95% CI: 36.81%, 48.06%) for apolipoprotein B; increases in HDL-C of 5.97% (95% CI: 4.59%, 7.35%) were also observed. There was no significant difference in fasting plasma glucose (FPG) (WMD: 2.02 mg/mL; 95% CI: −1.83, 5.87) and HbA1c (WMD: 1.82%; 95% CI: −0.63, 4.27). Use of a PCSK9 inhibitor was not associated with increased risk of treatment-emergent adverse event (TEAE) (p = 0.542), serious adverse event (SAE) (p = 0.529) and discontinuations due to AEs (p = 0.897).ConclusionsPCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease.Registration code in prosperoCRD42022339785.     

Triglycerides and Residual Atherosclerotic Risk

BackgroundEven when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.ObjectivesThis study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.MethodsAn observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.ResultsAtherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003).ConclusionsIn individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)     

Association between serum uric acid levels and cardiovascular risk factors among adults in India

Background and aimThe objective of this study was to explore the association between serum uric acid (SUA) levels and cardiovascular risk factors in the Indian population.Methods and resultsThis was a cross-sectional, population-based study. The study enrolled adults aged 20 years and above residing in rural, sub-urban, and urban. All participants completed a detailed questionnaire, underwent anthropometric measurements, and had blood samples collected. Participants were divided into three tertiles based on their SUA concentrations. A total of 2976 participants were included in this study, with 865 from rural, 1030 from sub-urban, and 1081 from urban populations. The mean values of cardiovascular risk factors were significantly higher in tertile 3 (p < 0.001) as compared to the other tertiles. However, we observed a negative trend between the increase of SUA and SUA/Scr ratio and HbA1c levels (Pearson correlation r = −0.068; p < 0.001 and r = −0.140; p < 0.001, respectively). The healthy and prediabetic groups did not show any significant change in HbA1c with increasing SUA levels, while an inverse trend was observed in diabetics. In the diabetic population, both men and women showed an inverse trend between increasing SUA levels and HbA1c in both known and newly diagnosed diabetes (p < 0.001).ConclusionsThe study found a positive association between SUA levels and cardiovascular risk factors. However, HbA1c was inversely correlated with increasing SUA tertiles in both known and newly diagnosed diabetes, as compared to the general population. Additionally, both men and women with diabetes consistently showed an inverse relationship between increasing SUA/SCr ratio and HbA1c levels.     

Cardiovascular magnetic resonance characterization of myocardial and vascular function in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a multisystem, autoimmune disorder and confers one of the strongest risks for cardiovascular disease (CVD) morbidity and mortality.ObjectiveTo assess myocardial function and vascular stiffness in RA patients with and without cardiovascular risk factors (CVRFs) using cardiovascular magnetic resonance (CMR).MethodsTwenty-three RA patients with no CVRFs (17 female, mean age 52 ± 13 years), 46 RA patients with CVRFs (32 female, mean age 53 ± 12), 50 normal controls (32 female, mean age 50 ± 11 years), and 13 controls with CVRFs (7 female, mean age 55 ± 7 years), underwent CMR at 1.5 Tesla, including evaluation of left ventricular (LV) ejection fraction, strain, and vascular elasticity (aortic distensibility [AD] and pulse wave velocity [PWV]). Disease activity and duration were recorded for each patient. Subjects with known symptomatic CVD were excluded.ResultsLV volumes, mass, and ejection fraction were similar in the four groups. RA patients with CVRFs showed the greatest abnormality in mid short-axis circumferential systolic strain, peak diastolic strain rate, and vascular indices. RA patients without CVRFs showed a similar degree of vascular dysfunction and deformational abnormality as controls with CVRFs. AD and total PWV correlated with myocardial strain and RA disease activity. On multivariate regression analysis, strain was related to age, RA disease activity, AD, and PWV.ConclusionCMR demonstrates impaired myocardial deformation and vascular function in asymptomatic RA patients, worse in those with CVRFs. Subclinical cardiovascular abnormalities are frequent and appear to be incremental to those due to traditional CVRFs and likely contribute to the excess CVD in RA.     

Pre-Diabetes Increases Stroke Risk in Patients With Nonvalvular Atrial Fibrillation

BackgroundDiabetes mellitus (DM) increases the risk of embolism in nonvalvular atrial fibrillation (NVAF). The association between pre-diabetes and risk of ischemic stroke has not been studied separately in this population.ObjectivesThe purpose of this study was to evaluate whether pre-diabetes is associated with increased risk of stroke and death in patients with NVAF.MethodsWe conducted a historical cohort study using the Clalit Health Services electronic medical records. The study population included all members aged ≥25 years, with a first diagnosis of NVAF between January 1, 2010, and December 31, 2016. We compared 3 groups of individuals: those with pre-diabetes, those with diabetes, and normoglycemic patients.ResultsA total of 44,451 cases were identified. The median age was 75 years, and 52.5% were women. During a mean follow-up of 38 months, the incidence rates of stroke (per 100 person-years) were: 1.14 in normoglycemic individuals, 1.40 in those with pre-diabetes, and 2.15 in those with diabetes. In both univariate and multivariate analyses, pre-diabetes was associated with an increased risk of stroke compared with normoglycemic persons (adjusted hazard ratio [adjHR]: 1.19; 95% confidence interval [CI]: 1.01 to 1.4) even after adjustment for CHA₂DS₂-Vasc risk factors and use of anticoagulants, while diabetes conferred an even higher risk (vs. normoglycemia (adjHR: 1.56; 95% CI: 1.37 to 1.79). The risk for mortality was higher for individuals with diabetes (adjHR: 1.47; 95% CI: 1.41 to 1.54) but not for those with pre-diabetes (adjHR: 0.98; 95% CI: 0.92 to 1.03).ConclusionsIn this cohort of patients with incident NVAF, pre-diabetes was associated with an increased risk of stroke even after accounting for other recognized risk factors.     

Dulaglutide reduces binge episodes in type 2 diabetic patients with binge eating disorder: A pilot study

AimsBinge eating disorder (BED) is the most common eating disorder in the United States and Europe and is associated with obesity and type 2 diabetes (T2D). Presence and severity of BED have been associated with worse metabolic control and greater BMI in T2D patients. Glucagon Like Peptide-1 (GLP1) receptors are present in central nervous system areas involved in appetite regulation and treatment with GLP-1 receptor agonists modulates appetite and reward-related brain areas in humans. We evaluated the effects of treatment with dulaglutide on eating behavior in T2D outpatients with BED.MethodsThis was a pilot open label, prospective controlled study. Inclusion criteria were: Age ≤65, HbA1c between 7.5 and 9% on metformin therapy alone, normal renal function and diagnosis of BED. Patients were randomly assigned to receive either Dulaglutide 1,5 mg/sett or Gliclazide 60 mg for 12 weeks. We evaluated baseline binge eating scale score (BES), weight, BMI, percentage fat mass, HbA1c and their changes after treatment. A multivariate linear regression model was used to verify the association between Δ BES from baseline with Δ Hba1c and variation of anthropometric parameters after treatment.ResultsAfter 12 weeks patients treated with dulaglutide had grater reduction of binge eating behaviour (p < 0.0001), body weight (p < 0,0001), BMI (p < 0.0001), percentage fat mass (p < 0.0001) and HbA1c (p = 0.009) than patients treated with gliclazide. Reduction in BES was associated with reduction in body weight (p < 0.0001) and HbA1c (p = 0.033).ConclusionDulaglutide treatment reduces binge eating behaviour in T2D patients with BED.     

Short-Term Progression of Multiterritorial Subclinical Atherosclerosis

BackgroundAtherosclerosis progression predicts cardiovascular events; however, progression of multiterritorial subclinical atherosclerosis is incompletely understood.ObjectivesThis study sought to study short-term progression of atherosclerosis using different noninvasive imaging techniques and their relationship with cardiovascular risk.MethodsThe study included 3,514 PESA (Progression of Early Subclinical Atherosclerosis) study participants (45.7 ± 4.2 years of age; 63% men). Participants underwent 2-dimensional vascular ultrasound (2DVUS) of abdominal aorta, carotid, iliac, and femoral territories to determine a plaque number score; 3DVUS to quantify carotid and femoral plaque volume; and coronary artery calcium score (CACS) at baseline and 2.8 years later. The authors calculated the rate of new disease incidence and changes in disease extent. Logistic regression models were used to evaluate associations of progression rates with baseline cardiovascular risk factors and estimated 10-year risk.ResultsImaging detected short-term (3-year) atherosclerosis progression in 41.5% of participants (26.4% by 2DVUS, 21.3% by 3DVUS, and 11.5% by CACS), particularly in peripheral territories examined by vascular ultrasound. New atherosclerosis onset accounted for approximately one-third of total progression, also more frequently by 2DVUS and 3DVUS (29.1% and 16.6%, respectively), than by CACS (2.9%). Participants with baseline disease by all 3 modalities (n = 432) also showed significant atherosclerosis progression (median: 1 plaque [interquartile range (IQR): −1 to 3 plaques] by 2DVUS; 7.6 mm³ [IQR: −32.2 to 57.6 mm³] by 3DVUS; and 21.6 Agatston units [IQR: 4.8 to 62.6 Agatston units] by CACS). Age, sex, dyslipidemia, hypertension, smoking, and family history of premature cardiovascular disease contributed to progression, with dyslipidemia the strongest modifiable risk factor. Although disease progression correlated with cardiovascular risk, progression was detected in 36.5% of participants categorized as low risk.ConclusionsWith this multimodal and multiterritorial approach, the authors detected short-term progression of early subclinical atherosclerosis in a substantial proportion (41.5%) of apparently healthy middle-aged men and women, more frequently by peripheral 2D/3DVUS than by CACS. Disease progression, as defined in this study, correlated with almost all cardiovascular risk factors and estimated risk. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)     

Concurrence of hyperinsulinemia and hyperuricemia significantly augmented all-cause mortality

Background and aimsHyperinsulinemia and hyperuricemia are known to increase the risk of mortality due to certain complications, such as Type 2 Diabetes and cardiovascular disease. However, despite their common comorbidities, their combined effect has not been evaluated. The study's aim was to evaluate the combine effect of hyperinsulinemia and hyperuricemia on all-cause mortality.Methods and resultsNHANES datasets (cycles 2003–2018) were examined. Differences between groups were evaluated using Rao-Scott Chi-square and General Linear Model for categorical and continuous data, respectively. Hazard Ratios (HR) were calculated using Cox regression with 95% confidence intervals (95%CI). There was significant difference (p < 0.05) in the mortality rate between the control group (2.3 ± 0.2%), the hyperinsulinemia only group (3.1 ± 0.3%), the hyperuricemia only group (4.0 ± 0.8%), and both conditions (5.1 ± 0.8%). Individually, when compared to the control group, there was a significant increase in mortality risk for hyperinsulinemia (HR: 1.50, 95%CI: 1.12–2.01, p = 0.007) and hyperuricemia (HR: 1.80, 95%CI:1.18–2.75, p = 0.006). However, when both conditions were present, there appeared an additive effect in the mortality risk (HR: 2.32, 95%CI: 1.66–3.25, p < 0.001). When stratified by BMI class, only normal weight participants presented with a significant risk (HR: 7.00, 95%CI: 2.50–20.30, p < 0.001). Also, when stratified by age, only participants older than 40 years presented a risk (HR: 2.22, 95%CI: 1.56–3.16, p < 0.001).ConclusionAlone, hyperuricemia and hyperinsulinemia significantly increased the mortality rate; however, the combined presence of both pathologies was associated with a significantly augmented mortality rate. Normal weight participant or that were >40 years old had a greater risk for mortality.     

Dose-dependent efficacy and safety of licogliflozin on obese adults: A systematic review and meta-analysis of randomized controlled trials

Background and aimLicogliflozin is a dual SGLT1/2 inhibitor acting on the intestine and kidney by reducing glycemic and calorie content. We aimed to determine the efficacy and safety of licogliflozin on Anthropometric measurements and cardiometabolic parameters in obese participants.MethodsWe systematically searched the PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials (RCTs) relevant to our eligibility criteria. We performed a subgroup analysis based on licogliflozin doses and the diabetic state of participants. This meta-analysis was registered on PROSPERO (CRD42021286936).ResultsWe identified five RCTs with a total of 905 obese and overweight participants. All participants had a weight reduction of 2.43 kg (95% CI: ?3.17 to ?1.69, p < 0.00001) compared with placebo. The mean difference in HbA1c of obese diabetic patients was (MD: ?0.30%; 95% CI: ?0.45, ?0.16); I2 = 46% in favor of licogliflozin. The incidence of serious adverse events, all-cause mortality, headache, nausea, and vomiting were similar between licogliflozin and placebo (p = 0.72, 0.97, 0.09, 0.53, and 0.89, respectively). However, there was a higher incidence of diarrhea in the licogliflozin group.ConclusionWe found that licogliflozin was safe and tolerable. It reduces body weight significantly. Moreover, it improves glycemic control and other cardiometabolic parameters.     

In-Stent CTO Percutaneous Coronary Intervention: Individual Patient Data Pooled Analysis of 4 Multicenter Registries

ObjectivesThe authors sought to examine the outcomes of percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) chronic total occlusions (CTOs).BackgroundThe outcomes of PCI for ISR CTOs have received limited study.MethodsThe authors examined the clinical and angiographic characteristics and procedural outcomes of 11,961 CTO PCIs performed in 11,728 patients at 107 centers in Europe, North America, Latin America, and Asia between 2012 and 2020, pooling patient-level data from 4 multicenter registries. In-hospital major adverse cardiovascular events (MACE) included death, myocardial infarction, stroke, and tamponade. Long-term MACE were defined as the composite of all-cause death, myocardial infarction, and target vessel revascularization.ResultsISR represented 15% of the CTOs (n = 1,755). Patients with ISR CTOs had higher prevalence of diabetes (44% vs. 38%; p < 0.0001) and prior coronary artery bypass graft surgery (27% vs. 24%; p = 0.03). Mean J-CTO (Multicenter CTO Registry in Japan) score was 2.32 ± 1.27 in the ISR group and 2.22 ± 1.27 in the de novo group (p = 0.01). Technical (85% vs. 85%; p = 0.75) and procedural (84% vs. 84%; p = 0.82) success was similar for ISR and de novo CTOs, as was the incidence of in-hospital MACE (1.7% vs. 2.2%; p = 0.25). Antegrade wiring was the most common successful strategy, in 70% of ISR and 60% of de novo CTOs, followed by retrograde crossing (16% vs. 23%) and antegrade dissection and re-entry (15% vs. 16%; p < 0.0001). At 12 months, patients with ISR CTOs had a higher incidence of MACE (hazard ratio: 1.31; 95% confidence interval: 1.01 to 1.70; p = 0.04).ConclusionsISR CTOs represent 15% of all CTO PCIs and can be recanalized with similar success and in-hospital MACE as de novo CTOs.     

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction

Background and aimsLow serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients.Methods and resultsMulticenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4–41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71–12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37–0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS −0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30–9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99–14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02–18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21–10.80, p = 0.022) were associated with AEs.ConclusionLow SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.     

Pericardial Fat and the Risk of Heart Failure

BackgroundObesity is a well-established risk factor for heart failure (HF). However, implications of pericardial fat on incident HF is unclear.ObjectivesThis study sought to examine the association between pericardial fat volume (PFV) and newly diagnosed HF.MethodsThis study ascertained PFV using cardiac computed tomography in 6,785 participants (3,584 women and 3,201 men) without pre-existing cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis). Cox proportional hazards regression was used to evaluate PFV as continuous and dichotomous variable, maximizing the J-statistic: (Sensitivity + Specificity – 1).ResultsIn 90,686 person-years (median: 15.7 years; interquartile range: 11.7 to 16.5 years), 385 participants (5.7%; 164 women and 221 men) developed newly diagnosed HF. PFV was lower in women than in men (69 ± 33 cm³ vs. 92 ± 47 cm³; p < 0.001). In multivariable analyses, every 1-SD (42 cm³) increase in PFV was associated with a higher risk of HF in women (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.21 to 1.71; p < 0.001) than in men (HR: 1.13; 95% CI: 1.01 to 1.27; p = 0.03) (interaction p = 0.01). High PFV (≥70 cm³ in women; ≥120 cm³ in men) conferred a 2-fold greater risk of HF in women (HR: 2.06; 95% CI: 1.48 to 2.87; p < 0.001) and a 53% higher risk in men (HR: 1.53; 95% CI: 1.13 to 2.07; p = 0.006). In sex-stratified analyses, greater risk of HF remained robust with additional adjustment for anthropometric indicators of obesity (p ≤ 0.008), abdominal subcutaneous or visceral fat (p ≤ 0.03) or biomarkers of inflammation and hemodynamic stress (p < 0.001) and was similar among Whites, Blacks, Hispanics, and Chinese (interaction p = 0.24). Elevated PFV predominantly augmented the risk of HF with preserved ejection fraction (p < 0.001) rather than reduced ejection fraction (p = 0.31).ConclusionsIn this large, community-based, ethnically diverse, prospective cohort study, pericardial fat was associated with an increased risk of HF, particularly HF with preserved ejection fraction, in women and men.     

Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality

BackgroundReduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.ObjectivesThis study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.MethodsA total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.ResultsAn increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.ConclusionsGenetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population.     

Coronary Access After TAVR-in-TAVR as Evaluated by Multidetector Computed Tomography

ObjectivesThe aim of this study was to assess coronary accessibility after transcatheter aortic valve replacement (TAVR)–in–TAVR using multidetector computed tomography.BackgroundExpanding TAVR to patients with longer life expectancy may involve more frequent bioprosthetic valve failure and need for redo TAVR. Coronary access after TAVR-in-TAVR may be challenging, particularly as the leaflets from the initial transcatheter heart valve (THV) will form a neo-skirt following TAVR-in-TAVR.MethodsIn 45 patients treated with different combinations of CoreValve and Evolut (CV/EV) THVs with supra-annular leaflet position and SAPIEN THVs with intra-annular leaflet position, post-TAVR-in-TAVR multidetector computed tomographic scans were analyzed to examine coronary accessibility.ResultsAfter TAVR-in-TAVR, the coronary arteries originated below the top of the neo-skirt in 90% of CV/EV-first cases compared with 67% of SAPIEN-first cases (p = 0.009). For these coronary arteries originating below the top of the neo-skirt, the distance between the THV and the aortic wall was <3 mm in 56% and 25% of CV/EV-first and SAPIEN-first cases, respectively (p = 0.035). Coronary access may be further complicated by THV-THV stent frame strut misalignment in 53% of CV/EV-in-CV/EV cases. The risk for technically impossible coronary access was 27% and 10% in CV/EV-first and SAPIEN-first cases, respectively (p = 0.121). Absence of THV interference with coronary accessibility can be expected in 8% and 33% of CV/EV-first and SAPIEN-first cases, respectively (p = 0.005).ConclusionsCoronary access after TAVR-in-TAVR may be challenging in a significant proportion of patients. THVs with intra-annular leaflet position or low commissural height and large open cells may be preferable in terms of coronary access after TAVR-in-TAVR.     

Impact of metabolically healthy obesity on carotid intima-media thickness - The Brazilian Longitudinal Study of Adult Health

Background and aimsObesity increases the risk of metabolic abnormalities, which contributes to elevated cardiovascular risk. However, the independent role of obesity in the development of cardiovascular disease is still debatable. There are individuals with an obesity phenotype without metabolic abnormalities: “metabolically healthy obesity” (MHO). This study evaluates the association between MHO and carotid intima-media thickness (CIMT), an early marker of subclinical atherosclerosis.Methods and resultsThis is a cross-sectional analysis of the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We used a strict definition to classify MHO: body mass index ≥30 kg/m² and meeting none of the four metabolic syndrome criteria. Data from 10,335 participants were analyzed. The obesity prevalence in our population was 21.2% (n = 2191). The prevalence of MHO was 5.6% (n = 124). When individuals were stratified according to metabolic health, we found the metabolically healthy individuals were younger, more likely to be women and never smokers. The mean CIMT of the sample was 0.81 mm (±0.20). The mean CIMT of the metabolically healthy subsample was 0.70 mm (±0.13) in individuals without obesity and 0.76 mm (±0.13) in individuals with obesity (p < 0.001). The mean CIMT of the metabolically unhealthy subsample was 0.81 mm (±0.20) in individuals without obesity and 0.88 mm (±0.20) in individuals with obesity (p < 0.001). These findings remained essentially unchanged after multivariate adjustment for confounding factors.ConclusionThe concept of MHO, even with the strict definition, seems inadequate, as even in this population, obesity is associated with higher CIMT levels.     

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

BackgroundTHEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA_1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.ObjectivesIn these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction–defined major bleeding) and net clinical benefit varied with diabetes-related factors.MethodsOutcomes were analyzed across baseline diabetes duration, HbA_1c, and antihyperglycemic medications.ResultsIn THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA_1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA_1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA_1c, and antihyperglycemic medications.ConclusionTicagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.