Dapagliflozin Reduces Systemic Inflammation in Patients with Type 2 Diabetes Without Known Heart Failure.

Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis. Research and Design Methods: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); cardiac tissue inflammation was assessed by T2 mapping. Results: Between the baseline and 12-month time point, plasma IL-1B was reduced (-1.8 pg/mL, P=0.003) while ketones were increased (0.26 mM, P=0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (-158.9 pmole/min/106cells, P=0.0497 vs -45.2 pmole/min/106cells, P=0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. ECV and T2 relaxation time did not change in both study groups. Conclusion: This study demonstrates that 12 months of dapagliflozin reduces IL-1B mediated systemic inflammation but affect cardiac fibrosis in T2D. Clinical Trialgov Registration: NCT03782259.

Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH.

BACKGROUND: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. METHODS: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. RESULTS: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). CONCLUSIONS: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01178320.

Prognostic Value of NT-proBNP in Patients With Successful PCI for ACS and Normal Left Ventricular Ejection Fraction.

BACKGROUND: Patients undergoing successful percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) with normal left ventricular ejection fraction (LVEF) are generally considered to have successful clinical outcomes; however, there are still significant differences in clinical outcomes among these patients. The aim of the study was to find a common indicator to predict the risk of major adverse cardiac and cerebrovascular events (MACCE) in this population. METHODS: A total of 3986 patients with ACS were divided into 4 groups based on the quartile (Q) values of peak N-Terminal pro-brain natriuretic peptide (NT-proBNP) measured during hospitalization. The incidence of MACCE was compared among Q1-Q4 groups during follow up. Multivariate Cox regression analysis was performed to identify independent prognostic factors of MACCE. Receiver operating characteristic (ROC) curve was generated to compare the area under the curve (AUC) for MACCE by adding NT-proBNP to the Thrombolysis in Myocardial Infarction (TIMI) risk score. RESULTS: NT-proBNP was significantly positively correlated with peak values of cardiac troponin I (cTnI) (r = 0.418), high-sensitivity C-reactive protein (hs-CRP) (r = 0.397) and left ventricular end-diastolic diameter (LVEDD) (r = 0.075) (P < 0.001). The risks of composite MACCE (5.6%, 9.1%, 13.0%, 20.1%, P < 0.001), all-cause death (1.0%, 2.5%, 4.1%, 8.4%, P < 0.001) and non-fatal myocardial infarction (2.0%, 3.4%, 4.8%, 6.2%, P < 0.001) were significantly higher in the higher Q groups. In multivariate analysis, the Q4 group displayed an independent 2.2-fold increase for MACCE compared to Q1 (HR: 2.16; 95%CI: 1.57-2.99; P < 0.001). Compared with TIMI risk score alone, TIMI+NT-proBNP showed improved AUCs: cardiovascular death (P = 0.0008), and heart failure requiring hospitalization (P = 0.0017). CONCLUSIONS: In patients with ACS with successful PCI and normal LVEF, elevated NT-proBNP was significantly associated with poor clinical outcomes. These results suggest that NT-proBNP is a useful biomarker for prognosis and risk stratification in this population.

High Triglyceride-Glucose Index is Associated with Poor Cardiovascular Outcomes in Nondiabetic Patients with ACS with LDL-C below 1.8 mmol/L.

AIM: To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L. METHODS: A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2]. RESULTS: Compared with the TyG index ＜8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p=0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p=0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p=0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p=0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index ＜8.33 group (8.9% vs. 5.0%, p=0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02-2.75; p=0.043]. CONCLUSIONS: In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.

Altered serum calcium homeostasis independently predicts mortality in patients with acute coronary syndrome: a retrospective observational cohort study.

OBJECTIVES: Serum calcium levels (sCa) were reported to be associated with risk of cardiovascular diseases. The aim of this study was to analyse the association between sCa and long-term mortality in patients with acute coronary syndrome (ACS). DESIGN: A retrospective observational cohort study. SETTING: Single-centre study with participants recruited from the local area. PARTICIPANTS: A total of consecutive 13 772 patients with ACS were included in this analysis. Patients were divided based on their sCa profile (≤2.1 mmol/L, 2.1-2.2 mmol/L, 2.2-2.3 mmol/L, 2.3-2.4 mmol/L, 2.4-2.5 mmol/L,>2.5 mmol/L) and followed up for a median of 2.96 years (IQR 1.01-4.07). PRIMARY OUTCOME: Long-term all-cause mortality. RESULTS: During a median follow-up period of 2.96 years, patients with sCa ≤2.1 mmol/L had the highest cumulative incidences of all-cause mortality (16.7%), whereas those with sCa 2.4-2.5 mmol/L had the lowest cumulative incidences of all-cause mortality (3.5%). After adjusting for potentially confounding variables, the Cox analysis revealed that compared with the reference group (sCa 2.4-2.5 mmol/L), all the other groups had higher mortality except for the sCa 2.3-2.4 mmol/L group (HR, 1.32, 95% CI 0.93 to 1.87). Restricted cubic splines showed that the relationship between sCa and all-cause mortality seemed to be U shaped. The optimal sCa cut-off point, 2.35 mmol/L, was determined based on the shape of restricted cubic splines. CONCLUSIONS: Altered serum calcium homeostasis at admission independently predicts all-cause mortality in patients with ACS. In addition, a U-shaped relationship between sCa and all-cause mortality exists, and maintaining sCa at approximately 2.35 mmol/L may minimise the risk of mortality.

Metabolic and inflammatory risk reduction in response to lipid-lowering and lifestyle modification in the medically underserved individuals.

INTRODUCTION: Medically underserved (US) populations have an increased level of atherosclerotic cardiovascular disease (ASCVD) risk, however, few studies investigated ASCVD risk reduction in US. METHODS: Of 217 subjects with ApoB ≥120 mg/dL and carotid atherosclerosis (≥15% stenosis by ultrasound) enrolled in the Carotid Plaque Composition by MRI (CPC) study between 2005 and 2011, US (n=33) was defined as those without adequate healthcare insurance, while AS (n=184) included those with adequate healthcare coverage. All subjects received atorvastatin-based lipid therapies and lifestyle intervention for 2 years. Metabolic and inflammatory risk factors were compared between AS and US. RESULTS: At baseline, compared to AS, US displayed higher levels of metabolic and inflammatory risk including systolic blood pressure (140±27 vs. 131±18 mmHg, p=0.04), fasting glucose (125±59 vs. 102±22 mg/dL, p=0.03) and fasting insulin (39±33 vs. 28±20 µU/dL, p=0.03) which resulted in higher insulin resistance (HOMA-IR 2.2±0.4 vs. 1.3±0.1, p=0.03), and hsCRP (5.6±1.5 vs. 2.8±0.2 mg/L, p=0.03). Over 2 years of intervention, US and AS showed similar reductions in LDL-C (-10.7% vs. -16% per year, p=0.2), triglycerides (-16.7% vs. -15.9% per year, p=0.4), and hsCRP (-0.11% vs. -0.04% per year, p=0.1). However, US continued to show significantly higher levels of fasting blood glucose (115±6.0 vs. 101±2.0 mg/dL, p=0.03) and HOMA-IR (1.9±0.2 vs. 1.5±0.1, p=0.047), and hsCRP (3.9±0.7 vs. 1.9±0.2 mg/L, p<0.001) than AS following 2 years of interventions. CONCLUSIONS: US displayed higher ASCVD risk than AS at baseline and over 2 years despite similar reductions following the intervention. These findings highlight the unmet needs for improved intervention strategies and implementation methods for ASCVD risk reduction in US. CLINICAL TRIAL REGISTRATION: NCT00715273 at ClinicalTrials.gov.

Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects.

OBJECTIVE: Niacin therapy fails to reduce cardiovascular events in statin-treated subjects even though it increases plasma HDL-C (HDL [high-density lipoprotein] cholesterol) and decreases LDL-C (LDL [low-density lipoprotein] cholesterol) and triglyceride levels. To investigate potential mechanisms for this lack of cardioprotection, we quantified the HDL proteome of subjects in 2 niacin clinical trials: the CPC study (Carotid Plaque Composition) and the HDL Proteomics substudy of the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides). APPROACH AND RESULTS: Using targeted proteomics, we quantified levels of 31 HDL proteins from 124 CPC subjects and 120 AIM-HIGH subjects. The samples were obtained at baseline and after 1 year of statin monotherapy or niacin-statin combination therapy. Compared with statin monotherapy, niacin-statin combination therapy did not reduce HDL-associated apolipoproteins APOC1, APOC2, APOC3, and APOC4, despite significantly lowering triglycerides. In contrast, niacin markedly elevated HDL-associated PLTP (phospholipid transfer protein), CLU (clusterin), and HP/HPR (haptoglobin/haptoglobinrelated proteins; P≤0.0001 for each) in both the CPC and AIM-HIGH cohorts. CONCLUSIONS: The addition of niacin to statin therapy resulted in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, which might have compromised the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00715273; NCT00880178; NCT00120289.

Regression in carotid plaque lipid content and neovasculature with PCSK9 inhibition: A time course study.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events, but their effects on atherosclerotic plaque remain elusive. Using serial magnetic resonance imaging (MRI), we studied changes in carotid plaque lipid content and neovasculature under PCSK9 inhibition with alirocumab. METHODS: Among patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl but ineligible for high-dose statin therapy, those with lipid core on carotid MRI were identified to receive alirocumab 150 mg every 2 weeks. Follow-up MRI was performed at 3, 6, and 12 months after treatment. Pre- and post-contrast MRI were acquired to measure percent lipid core volume (% lipid core). Dynamic contrast-enhanced MRI was acquired to measure the extravasation rate of gadolinium contrast (Ktrans), a marker of plaque neovasculature. RESULTS: Of 31 patients enrolled, 27 completed the study (mean age: 69 ± 9; male: 67%). From 9.8% at baseline, % lipid core was progressively reduced to 8.4% at 3 months, 7.5% at 6 months, and 7.2% at 12 months (p = 0.014 for trend), which was accompanied by a progressive increase in % fibrous tissue (p = 0.009) but not % calcification (p = 0.35). Ktrans was not reduced until 12 months (from 0.069 ± 0.019 min-1 to 0.058 ± 0.020 min-1; p = 0.029). Lumen and wall areas did not change significantly during the study period. CONCLUSIONS: Regression in plaque composition and neovasculature were observed under PCSK9 inhibition on carotid MRI, which provides unique insight into the biological process of plaque stabilization with disease-modifying therapies.

Improvement of long-term clinical outcomes by successful PCI in the very elderly women with ACS.

BACKGROUND: Whether very elderly women with acute coronary syndromes (ACS) should receive aggressive percutaneous coronary intervention (PCI) is still controversial. We assessed the effectiveness and long-term clinical outcomes of successful PCI in this population and identified prognostic factors which might contribute to the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in the very elderly female PCI cohort. METHODS: Female ACS patients aged ≥ 80 years were consecutively enrolled (n = 729) into the study. All the patients were divided into female PCI group (n = 232) and medical group (n = 497). MACCE was followed up, including non-fatal myocardial infarction (MI), stroke, heart failure requiring hospitalization (HFRH), cardiovascular (CV) death, and the composite of them. After propensity score matching (1:1), the incidences of MACCE were compared between the two groups. Clinical and coronary artery lesion characteristics were compared between the female PCI patients with (n = 56) and without MACCE (n = 176). Multivariate Cox regression analysis was performed to identify risk factors which independently associated with MACCE in the female PCI patients. MACCE of male PCI patients, who aged ≥ 80 years and hospitalized in the same period (n = 264), was also compared with that of the female PCI patients. RESULTS: A total of 32% very elderly female ACS patients received PCI in the present study. (1) Compared to female medical group, PCI procedure significantly alleviated the risks of MACCE: non-fatal MI (6.2% vs. 20.2%, P < 0.001), HFRH (10.9% vs. 22.5%, P = 0.012), CV death (12.4% vs. 28.7%, P < 0.001) and the composite MACCE (24.0% vs. 44.2%, P < 0.001) during the median follow-up period of 36 months. (2) Between very elderly female and male PCI patients, there were no significant differences in occurrence of MACCE (P = 0.232) and CV death (P = 0.951). (3) Multivariate Cox analysis revealed that ST-segment elevation myocardial infarction (STEMI) (HR 1.944, 95% CI 1.11-3.403, P = 0.02) and elevated log- N-Terminal pro-brain natriuretic peptide (NT-proBNP) (HR 1.689, 95% CI 1.029-2.773, P = 0.038) were independently associated with the incidence of MACCE in the female PCI patients. CONCLUSIONS: PCI procedure significantly attenuated the risk of MACCE and improved the long-term clinical outcomes in very elderly female ACS patients. Aggressive PCI strategy may be reasonable in this population.

Predictive effect of triglyceride­glucose index on clinical events in patients with type 2 diabetes mellitus and acute myocardial infarction: results from an observational cohort study in China.

BACKGROUND: Triglyceride glucose (TyG) index is considered a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular (CV) outcomes. However, the prognostic value of TyG index in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) remains unclear. METHODS: A total of 1932 consecutive patients with T2DM and AMI were enrolled in this study. Patients were divided into tertiles according to their TyG index levels. The incidence of major adverse cardiac and cerebral events (MACCEs) was recorded. The TyG index was calculated as the ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. RESULTS: Competing risk regression revealed that the TyG index was positively associated with CV death [2.71(1.92 to 3.83), p < 0.001], non-fatal MI [2.02(1.32 to 3.11), p = 0.001], cardiac rehospitalization [2.42(1.81 to 3.24), p < 0.001], revascularization [2.41(1.63 to 3.55), p < 0.001] and composite MACCEs [2.32(1.92 to 2.80), p < 0.001]. The area under ROC curve of the TyG index for predicting the occurrence of MACCEs was 0.604 [(0.578 to 0.630), p < 0.001], with the cut-off value of 9.30. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for MACCEs [net reclassification improvement (NRI): 0.190 (0.094 to 0.337); integrated discrimination improvement (IDI): 0.027 (0.013 to 0.041); C-index: 0.685 (0.663 to 0.707), all p < 0.001]. CONCLUSIONS: The TyG index was significantly associated with MACCEs, suggesting that the TyG index may be a valid marker for risk stratification and prognosis in patients with T2DM and AMI. Trial registration Retrospectively registered.

Serial magnetic resonance imaging detects a rapid reduction in plaque lipid content under PCSK9 inhibition with alirocumab.

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events. Both can be noninvasively assessed with carotid MRI. We studied if PCSK9 inhibition with alirocumab induces regression in lipid-core or plaque inflammation within 6 months as measured by MRI. Patients with non-calcified carotid plaque(s) and baseline LDL-C ≥ 70 mg/dl, who were statin-intolerant or taking a low-dose statin (≤ 10 mg per day of atorvastatin or an equivalent), received subcutaneous alirocumab 150 mg every 2 weeks. Carotid MRI was performed at baseline and 6 months after treatment, including pre- and post-contrast images for measuring percent lipid-core volume (%LC) and dynamic contrast-enhanced images for measuring microvessel leakiness (Ktrans), a marker of inflammation. Twenty-eight patients completed the study (69 ± 9 years; 64% male). Alirocumab led to significant changes in LDL-C (p < 0.001) and high-density lipoprotein cholesterol (HDL-C) (p = 0.003). At 6 months, there was a significant reduction in %LC (mean: - 2.1% [- 3.5, - 0.7], p = 0.005; a 17% reduction from baseline of 9.9%) without significant changes in lumen/wall area or in the inflammatory index Ktrans. Carotid plaque lipid content was reduced by 17% after 6 months of PCSK9 inhibition with alirocumab. This was seen before observable changes in lumen or wall areas, which supports pursing plaque lipid content as a more sensitive marker of therapeutic response compared to lumen or wall areas in future technical developments and serial studies.

Poor cardiovascular health status among Chinese women.

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

High triglyceride-glucose index is associated with adverse cardiovascular outcomes in patients with acute myocardial infarction.

BACKGROUND AND AIMS: Triglyceride glucose (TyG) index is considered a new surrogate marker of insulin resistance that associated with the development of vascular disease. The aim of this study was to evaluate the prognostic value of TyG index in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 3181 patients with AMI were included in the analysis. Patients were stratified into 2 groups according to their TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. The incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), p = 0.010], cardiac death [HR (95% CI): 1.68 (1.19,2.38), p = 0.004], revascularization [HR (95% CI): 1.50 (1.16,1.94), p = 0.002], cardiac rehospitalization [HR (95% CI): 1.25 (1.05,1.49), p = 0.012], and composite MACEs [HR (95% CI): 1.19 (1.01,1.41), p = 0.046] in patients with AMI. The independent predictive effect of TyG index on composite MACEs was mainly reflected in the subgroups of male gender and smoker. The area under the curve (AUC) of the TyG index predicting the occurrence of MACEs in AMI patients was 0.602 [95% CI 0.580,0.623; p < 0.001]. CONCLUSION: High TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI. TRIAL REGISTRATION: Retrospectively registered.

Atherosclerosis, its risk factors, and cognitive impairment in older adults.

OBJECTIVE: To examine the association of atherosclerotic cardiovascular disease (ASCVD) and its risk factors with cognitive impairment in older adults. METHODS: Six hundred and fourteen subjects, aged ≥ 65 years, from one center (2016-2018) underwent clinical, laboratory assessments and the Montreal Cognitive Assessment (MoCA). Using regression analysis, the relationship between ASCVD and its risk factors was evaluated in subjects with and without cognitive impairment (MoCA score < 26). RESULTS: Older age (ß = -1.3 per 5 years, 95% CI: -1.7 to -0.9, P < 0.001), history of stroke (ß = -1.6, 95% CI: -3.0 to -0.3, P = 0.01), and myocardial infarction (MI; ß = -2.2, 95% CI: -3.6 to -0.8, P = 0.003) were independently associated with lower MoCA scores, whereas more education (ß = 1.5 per 3 years, 95% CI: 1.1 to 1.9, P < 0.001), higher body mass index (BMI; ß = 0.5 per 3 kg/m2, 95% CI: 0.0 to 1.0, P = 0.04), higher estimated glomerular filtration rate (eGFR; ß = 0.8 per 15 U, 95% CI: 0.1 to 1.4, P = 0.03), left ventricular ejection fraction (LVEF; ß = 0.4 per 5%, 95% CI: 0 to 0.8, P = 0.04) and statin use (ß = 1.3, 95% CI: 0.3 to 2.3, P = 0.01) were associated with a higher MoCA score. Cognitive impairment was independently associated with older age (OR = 1.51 per 5 yrs, 95% CI: 1.28 to 1.79, P < 0.001), less education (OR = 0.55 per 3 years, 95% CI: 0.45 to 0.68, P < 0.001), lower BMI (OR = 0.78 per 3 kg/m2, 95% CI: 0.62 to 0.98, P = 0.03) and higher levels of high sensitivity c-reactive protein (hsCRP; OR = 1.08 per 1 mg/L, 95% CI: 1.02 to 1.15, P = 0.01). CONCLUSIONS: Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.

Underweight Predicts Greater Risk of Cardiac Mortality Post Acute Myocardial Infarction.

Increased body mass index (BMI) is a well-established risk factor for cardiovascular disease; however, patients with elevated BMI, in comparison to those with low BMI, seem to have better survival, a phenomenon reported as "obesity paradox," which remains controversial. We investigated the effect of BMI on cardiac mortality post acute myocardial infarction (AMI).In this analysis, 3562 AMI patients were included and classified into four groups based on BMI values. The primary endpoint was cardiac death. Compared to normoweight group, overweight and obese group subjects were younger, mostly men, and more likely to receive percutaneous coronary intervention (PCI) and had higher levels of glucose and lipids, but lower level of NTproBNP. Subjects in the underweight group were older, were mostly women, had lower Barthel index (BI), were less likely to receive PCI, and had lower levels of glucose and lipids, but higher level of N-terminal pro-brain natriuretic peptide (NTproBNP) and higher rates of left ventricular ejection fraction (LVEF) < 50%. During a median follow-up period of 1.9 years, cardiac death occurred significantly more in the underweight group (30.0%, 10.6%, 7.0%, and 5.0% among the four groups from underweight to obese; P < 0.001 for trend). The Cox analysis revealed that underweight was an independent predictor of subsequent cardiac death (odds ratio (OR), 1.86; 95% confidence interval (CI), 1.07-3.25) and identified that older age, BI < 60, higher levels of cardiac troponin I (cTnI), LVEF < 50%, and not receiving PCI were independently associated with increased risk of cardiac death.Patients who were underweight were at greater risk of cardiac death post AMI. In addition, older age, frail, higher levels of cTnI, LVEF < 50%, and not receiving PCI also independently predicted cardiac mortality post AMI.

Real-world use of ACEI/ARB in diabetic hypertensive patients before the initial diagnosis of obstructive coronary artery disease: patient characteristics and long-term follow-up outcome.

BACKGROUND: Current guidelines recommend angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) as a first-line therapy in diabetic hypertensive patients and for secondary prevention in patients with obstructive coronary artery disease (OCAD). However, the effects of using ACEI/ARB before the initial diagnosis of OCAD on major adverse cardiac and cerebral event (MACCE) in diabetic hypertensive patients remain unclear. This study investigated whether using ACEI/ARB before the initial diagnosis of OCAD could be associated with improved clinical outcomes in diabetic hypertensive patients. METHODS: A total of 2501 patients with hypertension and diabetes, who were first diagnosed with OCAD by coronary angiography, were included in the analysis. Of the 2501 patients, 1300 did not used ACEI/ARB before the initial diagnosis of OCAD [the ACEI/ARB(-) group]; 1201 did [the ACEI/ARB(+) group]. Propensity score matching at 1:1 was performed to select 1050 patients from each group. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, heart function, and subsequent MACCE during a median of 25.4-month follow-up were determined and compared between the 2 groups. RESULTS: Compared with the ACEI/ARB(-) group, the ACEI/ARB(+) group had significantly lower incidence of AMI (22.5% vs. 28.4%, p < 0.05), smaller infarct size in patients with AMI (pTNI: 5.7 vs. 6.8 ng/ml, p < 0.05; pCKMB: 21.7 vs. 28.7 ng/ml, p < 0.05), better heart function (LVEF: 60.0 vs. 58.5%, p < 0.05), and lower incidences of non-fatal stroke (2.4% vs. 4.6%, p < 0.05) and composite MACCE (23.1% vs. 29.7%, p < 0.05). No prior ACEI/ARB therapy was significantly and independently associated with non-fatal stroke and composite MACCE. CONCLUSIONS: In diabetic hypertensive patients, treatment with ACEI/ARB before the initial diagnosis with OCAD was associated with decreased incidence of AMI, smaller infarct size, improved heart function, and lower incidences of non-fatal stroke and composite MACCE. Trial registration Retrospectively registered.

High-resolution MRI assessed carotid atherosclerotic plaque characteristics comparing men and women with elevated ApoB levels.

Previous studies demonstrated that men were more likely to have plaque rupture and are at greater risk for myocardial infarction and stroke than women. We evaluated differences in carotid plaque characteristics by MRI between men and women with mild-moderate atherosclerosis and elevated ApoB levels. One hundred eighty-two subjects (104 men and 78 women) with CAD or carotid stenosis (≥ 15% by ultrasound), ApoB ≥ 120 mg/dL and carotid MRI scan were included. Percent wall volume (%WV) was calculated as (wall volume/total vessel volume) × 100%. Three major plaque compositions, fibrous tissue (FT), calcification (CA) and lipid rich necrotic core (LRNC), were identified and quantified using published MRI criteria. Adventitial and plaque neovascularization as fractional plasma volume (Vp) and permeability as transfer constant (Ktrans) were analyzed using kinetic modeling. These characteristics were compared between men and women. Men, compared to women, were younger (54 ± 8 vs. 58 ± 8 years, p = 0.01), had higher rate of previous MI (46 vs. 26%, p = 0.005) but lower proportions of metabolic syndrome (37 vs. 59%, p = 0.003). After adjusting for between-gender differences, men were significantly more likely to have LRNC (OR 2.22, 95% CI 1.04-4.89, p = 0.04) and showed significantly larger %LRNC than women (diff = 4.3%, 95% CI 1.6-6.9%, p = 0.002), while %WV, FT, and CA were similar between men and women. There were no statistically significant differences in adventitial and plaque Vp or Ktrans. Men were significantly more likely to have LRNC and had larger LRNC than women. However, men and women showed relatively similar levels of adventitial and plaque neovascularization and permeability.Trial registration: NCT00715273 at ClinicalTrials.gov. Registered 15 July 2008, retrospectively registered.

Rapid improvement in carotid adventitial angiogenesis and plaque neovascularization after rosuvastatin therapy in statin treatment-naïve subjects.

BACKGROUND: Statin therapy can improve plaque stability. However, the time course of effects of statin on adventitial angiogenesis and plaque neovascularization has not been studied. OBJECTIVE: The objective of the study was to investigate whether statin therapy reduces plaque neovascularization, associated with adventitial angiogenesis, over 24 months as assessed by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: Forty-three lipid treatment-naïve subjects with asymptomatic carotid atherosclerosis received rosuvastatin (5-20 mg/d) to lower low-density lipoprotein cholesterol to <80 mg/dL for 24 months. Carotid DCE-MRI was performed at baseline, 3, 12 and 24 months. Vascularity (Vp = fractional plasma volume) and vascular permeability (Ktrans = transfer constant) derived from kinetic modeling of DCE-MRI were measured in both adventitia and plaque. RESULTS: Adventitia Vp and adventitia Ktrans were significantly correlated with plaque Vp and plaque Ktrans at baseline. Rosuvastatin significantly reduced both adventitial and plaque Vp significantly at 3 months from 0.121 ± 0.064 to 0.085 ± 0.049 (P = .008) and from 0.096 ± 0.052 to 0.067 ± 0.043 (P = .013). Adventitial and plaque Vp continued to decrease by 43% and 34% at 12 months and by 49% and 45% at 24 months. However, the continued reductions from 3 to 12 months and from 12 to 24 months were not statistically significant. Adventitial and plaque Ktrans showed similar trends, but nonstatistically significant decreases during the 24 months of treatment. CONCLUSIONS: Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization at 3 months followed by continued, but nonstatistically significant, decreases at 12 and 24 months.

High admission glucose levels predict worse short-term clinical outcome in non-diabetic patients with acute myocardial infraction: a retrospective observational study.

BACKGROUND: Patients with acute myocardial infarction (AMI) often accompanied by admission hyperglycemia, which usually predicts a poor clinical outcomes for non-diabetes mellitus. Appropriate cut-point to identify high risk individuals in these patients remains controversial. METHODS: One thousand six hundred ninety-eight non-diabetes AMI patients in this retrospective study were divided into 3 groups according to admission glucose levels (euglycemia group≤140 mg/dL, moderate hyperglycemia group 141-179 mg/dL, severe hyperglycemia group≥180 mg/dL). The primary endpoint of this study was all-cause in-hospital mortality rate. In-hospital motality related risk factors was analyzed by multivariate binary logistic regression analyses. RESULTS: All myocardial necrosis markers and Log NT-proBNP in severe hyperglycemia group were significantly higher than those in the other 2 groups. Logistic regression showed that independent predictors of the in-hospital mortality rate in non-diabetic patients with AMI were age (OR = 1.057, 95% CI 1.024-1.091, P < 0.001), logarithm of the N-terminal pro-brain natriuretic peptide (OR = 7.697, 95% CI 3.810-15.550, P < 0.001), insufficient myocardial reperfusion (OR = 7.654, 95% CI 2.109-27.779, P < 0.001), percutaneous coronary intervention (OR = 0.221, 95% CI 0.108-0.452, P < 0.001) and admission glucose (as categorical variable). Patients with moderate hyperglycemia (OR = 1.186, 95% CI 0.585-2.408, P = .636) and severe hyperglycemia (OR = 4.595, 95% CI 1.942-10.873, P = 0.001) had a higher all-cause in-hospital mortality rate compared with those with euglycemia after AMI in non-diabetic patients. CONCLUSIONS: The all-cause in-hospital mortality risk increases remarkably as admission glucose levels elevated in non-diabetic patients with AMI, especially in patients with admission glucose levels ≥180 mg/dL. Severe admission hyperglycemia could be regarded as prospective high-risk marker for non-diabetic AMI patients.

Usefulness of the CHA2DS2-VASc Score to Predict Adverse Outcomes in Acute Coronary Syndrome Patients Without Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

The prognostic value of the CHA2DS2-VASc score in acute coronary syndrome (ACS) patients without atrial fibrillation (AF) who underwent percutaneous coronary intervention remains uncertain. We examine the association of the CHA2DS2-VASc score and major adverse cardiovascular events (MACE) in this population and compared its risk prediction with 2 other commonly used risk scores (Global Registry of Acute Coronary Events [GRACE] and thrombolysis in myocardial infarction [TIMI]). A total of 3,745 consecutive ACS patients without AF who underwent percutaneous coronary intervention during 2013 to 2017 were classified into 4 groups according to the CHA2DS2-VASc score: low (0 to 1), moderate (2 to 3), high (4 to 5), and very high (>5). Incidences of MACE including cardiovascular death, nonfatal myocardial infarction, or stroke in-hospital and during a median follow-up of 33 months were compared among the 4 groups. Receiver-operating characteristic curves were generated to compare CHA2DS2-VASc with GRACE and TIMI for risk prediction. The incidences of in-hospital MACE (3.5%, 6.6%, 7.6%, and 9.1%, p <0.001) and mid-term follow-up MACE (4.5%, 7.1%, 13.1%, and 16.1%, p <0.001) were significantly higher as the CHA2DS2-VASc score increased. The CHA2DS2-VASc score was an independent predictor of subsequent MACE (hazard ratio = 1.31, 95% CI 1.24 to 1.39, p <0.001), and the very high-risk score group showed 3.8-fold increased risk of MACE than the low-risk score group. Receiver-operating characteristic curves showed that the CHA2DS2-VASc score was comparable to the GRACE score and to TIMI-STEMI, but, better than the TIMI-NSTEMI/unstable angina pectoris score in terms of predicting MACE. In conclusion, higher CHA2DS2-VASc score was independently associated with increased risk of MACE in the ACS patients without AF who underwent PCI.