Plasma Big Endothelin-1 Level Predicted 5-Year Major Adverse Cardiovascular Events in Patients With Coronary Artery Ectasia

Background: Coronary artery ectasia (CAE) is found in about 1% of coronary angiography and is associated with poor clinical outcomes. The prognostic value of plasma big Endothelin-1 (ET-1) in CAE remains unknown.Methods: Patients with angiographically confirmed CAE from 2009 to 2015, who had big ET-1 data available were included. The primary outcome was 5-year major adverse cardiovascular events (MACE), defined as a component of cardiovascular death and non-fatal myocardial infarction (MI). Patients were divided into high or low big ET-1 groups using a cut-off value of 0.58 pmol/L, according to the receiver operating characteristic curve. Kaplan-Meier method, propensity score method, and Cox regression were used to assess the clinical outcomes in the 2 groups.Results: A total of 992 patients were included, with 260 in the high big ET-1 group and 732 in the low big ET-1 group. At 5-year follow-up, 57 MACEs were observed. Kaplan-Meier analysis and univariable Cox regression showed that patients with high big ET-1 levels were at increased risk of MACE (9.87 vs. 4.50%; HR 2.23, 95% CI 1.32–3.78, P = 0.003), cardiovascular death (4.01 vs. 1.69%; HR 2.37, 95% CI 1.02–5.48, P = 0.044), and non-fatal MI (6.09 vs. 2.84%; HR 2.17, 95% CI 1.11–4.24, P = 0.023). A higher risk of MACE in the high big ET-1 group was consistent in the propensity score matched cohort and propensity score weighted analysis. In multivariable analysis, a high plasma big ET-1 level was still an independent predictor of MACE (HR 1.82, 95% CI 1.02–3.25, P = 0.043). A combination of high plasma big ET-1 concentrate and diffuse dilation, when used to predict 5-year MACE risk, yielded a C-statistic of 0.67 (95% CI 0.59–0.74).Conclusion: Among patients with CAE, high plasma big ET-1 level was associated with increased risk of MACE, a finding that could improve risk stratification.

Download Full-text

Prognostic value of ST2 for MACEs and all-cause mortality in patients with coronary artery disease during a long-term follow up

10.21203/rs.3.rs-63605/v1 ◽

2020 ◽

Author(s):

Man Li ◽

Lei Duan ◽

Yulun Cai ◽

Benchuan Hao ◽

Jianqiao Chen ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Prognostic Value ◽

Cox Regression ◽

Major Adverse Cardiovascular Events ◽

Kaplan Meier ◽

Increased Risk ◽

Artery Disease

Abstract Background: Suppression of tumorigenesis-2 is implicated in the myocardial overload and it was long been recognized as an inflammation marker related to heart failure and acute coronary syndromes, but the data on prognostic value of suppression of tumorigenesis-2 on patients with coronary artery disease remains limited. The study ought to investigate the prognostic value of suppression of tumorigenesis-2 in patients with established coronary artery disease.Methods: In this prospective cohort study, a total of 3641 consecutive patients were included. The primary end point was major adverse cardiovascular events. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). The secondary end point was all-cause death. The association between suppression of tumorigenesis-2 and outcomes was investigated using multivariable COX regression.Results: During a median follow up of 6.4 years, there were 775 patients had the occurrence of major adverse cardiovascular events and 275 patients died. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). Multiple COX regression models showed that higher level of suppression of tumorigenesis-2 was an independent predictor in developing major adverse cardiovascular events (HR=1.36, 95% CI 1.17-1.56, p＜0.001) and all-cause death (HR=2.01, 95%CI 1.56-2.59, p＜0.001). The addition of suppression of tumorigenesis-2 to established risk factors significantly improved risk prediction of the composite outcome of major adverse cardiovascular events and all-cause death (c-statistic, net reclassification index, and integrated discrimination improvement, all p＜0.05).Conclusions: Higher level of suppression of tumorigenesis-2 is significantly associated with long-term all-cause death and major adverse cardiovascular events. Suppression of tumorigenesis-2 may provide incremental prognostic value beyond traditional risk factors.

Download Full-text

Development and Validation of a Nomogram for Predicting the Risk of Adverse Cardiovascular Events in Patients with Coronary Artery Ectasia

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8120186 ◽

2021 ◽

Vol 8 (12) ◽

pp. 186

Author(s):

Zhongxing Cai ◽

Yintang Wang ◽

Luqi Li ◽

Haoyu Wang ◽

Chenxi Song ◽

...

Keyword(s):

Coronary Artery ◽

Cardiovascular Events ◽

Cox Regression ◽

High Sensitivity ◽

Quantitative Coronary Angiography ◽

Prognostic Scores ◽

Major Adverse Cardiovascular Events ◽

Lesion Length ◽

Coronary Artery Ectasia ◽

Validation Set

Coronary artery ectasia (CAE) is a rare finding and is associated with poor clinical outcomes. However, prognostic factors are not well studied and no prognostication tool is available. In a derivation set comprising 729 consecutive CAE patients between January 2009 and June 2014, a nomogram was developed using Cox regression. Total of 399 patients from July 2014 to December 2015 formed the validation set. The primary outcome was 5-year major adverse cardiovascular events (MACE), a component of cardiovascular death and nonfatal myocardial infarction. Besides the clinical factors, we used quantitative coronary angiography (QCA) and defined QCA classification of four types, according to max diameter (< or ≥5 mm) and max length ratio (ratio of lesion length to vessel length, < or ≥1/3) of the dilated lesion. A total of 27 cardiovascular deaths and 41 nonfatal myocardial infarctions occurred at 5-year follow-up. The nomogram effectively predicted 5-year MACE risk using predictors including age, prior PCI, high sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and QCA classification (area under curve [AUC] 0.75, 95% CI 0.68–0.82 in the derivation set; AUC 0.71, 95% CI 0.56–0.86 in the validation set). Patients were classified as high-risk if prognostic scores were ≥155 and the Kaplan–Meier curves were well separated (log-rank p < 0.001 in both sets). Calibration curve and Hosmer–Lemeshow test indicated similarity between predicted and actual 5-year MACE survival (p = 0.90 in the derivation and p = 0.47 in the validation set). This study developed and validated a simple-to-use method for assessing 5-year MACE risk in patients with CAE.

Download Full-text

Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia

Cardiology ◽

10.1159/000381702 ◽

2015 ◽

Vol 131 (4) ◽

pp. 251-259 ◽

Cited By ~ 6

Author(s):

Yan Zhang ◽

Qiao-Juan Huang ◽

Xiao-Lin Li ◽

Yuan-Lin Guo ◽

Cheng-Gang Zhu ◽

...

Keyword(s):

Coronary Artery ◽

Cardiovascular Events ◽

Prognostic Value ◽

Major Adverse Cardiovascular Events ◽

Type I ◽

Coronary Artery Ectasia ◽

Kaplan Meier ◽

Significant Difference ◽

The Right

Objectives: To assess the prognostic value of coexisting coronary artery disease (CAD), Markis class, and ectasia ratio for major adverse cardiovascular events in patients with coronary artery ectasia (CAE). Methods: A total of 512 consecutive patients with angiographically proven CAE were enrolled. Coronary ectasia extent was graded using the Markis class, and ectasia severity was assessed based on the ectasia ratio. Patients were followed up for a median of 34.6 months. Results: In the current study, 76 cases had isolated CAE, while the remaining 436 cases had coexisting CAD (mixture CAE). Males (84.4%) were predominantly affected, and the right coronary artery (55.1%) was most commonly involved. During follow-up, 86 overall major adverse cardiovascular events were diagnosed. Kaplan-Meier analysis failed to reveal any differences between isolated and mixture CAE in both cumulative and event-free survival analyses (p = 0.429 and p = 0.277, respectively). Moreover, when patients were divided into 4 groups according to Markis class (type I-IV) or 2 groups based on the ectasia ratio (1.5-2.0 and >2.0), there was no significant difference in survival outcomes among the groups (p > 0.05). Conclusions: In this follow-up study with a relatively large sample, the survival rate of patients with CAE appeared to be independent of coexisting CAD and ectasia extent and severity.

Download Full-text

Varicella zoster virus infections increase the risk of disease flares in patients with SLE: a matched cohort study

Lupus Science & Medicine ◽

10.1136/lupus-2019-000339 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000339 ◽

Cited By ~ 3

Author(s):

Fangfang Sun ◽

Yi Chen ◽

Wanlong Wu ◽

Li Guo ◽

Wenwen Xu ◽

...

Keyword(s):

Propensity Score ◽

Varicella Zoster Virus ◽

Cox Regression ◽

Control Period ◽

Cox Regression Analysis ◽

Varicella Zoster ◽

Propensity Score Weighting ◽

Kaplan Meier ◽

Increased Risk ◽

Risk Of Disease

ObjectiveTo explore whether varicella zoster virus (VZV) infection could increase the risk of disease flares in patients with SLE.MethodsPatients who had VZV reactivations between January 2013 and April 2018 were included from the SLE database (n=1901) of Shanghai Ren Ji Hospital, South Campus. Matched patients with SLE were selected as background controls with a 3:1 ratio. Patients with SLE with symptomatic bacterial infections of the lower urinary tract (UTI) were identified as infection controls. Baseline period and index period were defined as 3 months before and after infection event, respectively. Control period was the following 3 months after the index period. Flare was defined by SELENA SLEDAI Flare Index. Kaplan-Meier analysis, Cox regression model and propensity score weighting were applied.ResultsPatients with VZV infections (n=47), UTI controls (n=28) and matched SLE background controls (n=141) were included. 16 flares (34%) in the VZV group within the index period were observed, as opposed to only 7.1% in UTI controls and 9.9% in background controls. Kaplan-Meier curve revealed that patients with a VZV infection had a much lower flare-free survival within the index period compared with the controls (p=0.0003). Furthermore, after adjusting for relevant confounders including baseline disease activity and intensity of immunosuppressive therapy, Cox regression analysis and propensity score weighting confirmed that VZV infection within 3 months was an independent risk factor for SLE flares (HR 3.70 and HR 4.16, respectively).ConclusionsIn patients with SLE, recent VZV infection within 3 months was associated with increased risk of disease flares.

Download Full-text

Elevated Lp(a) (Lipoprotein[a]) Levels Increase Risk of 30-Day Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy

Stroke ◽

10.1161/strokeaha.120.030616 ◽

2020 ◽

Vol 51 (10) ◽

pp. 2972-2982 ◽

Cited By ~ 1

Author(s):

Farahnaz Waissi ◽

Mirthe Dekker ◽

Nathalie Timmerman ◽

Renate M. Hoogeveen ◽

Joelle van Bennekom ◽

...

Keyword(s):

Risk Factor ◽

Carotid Endarterectomy ◽

Cardiovascular Events ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Major Adverse Cardiovascular Events ◽

Lipoprotein A ◽

Kaplan Meier ◽

Increased Risk

Background and Purpose: General population studies have shown that elevated Lp(a) (lipoprotein[a]) levels are an emerging risk factor for cardiovascular disease and subsequent cardiovascular events. The role of Lp(a) for the risk of secondary MACE in patients undergoing carotid endarterectomy (CEA) is unknown. Our objective is to assess the association of elevated Lp(a) levels with the risk of secondary MACE in patients undergoing CEA. Methods: Lp(a) concentrations were determined in preoperative blood samples of 944 consecutive patients with CEA included in the Athero-Express Biobank Study. During 3-year follow-up, major adverse cardiovascular events (MACE), consisting of myocardial infarction, stroke, and cardiovascular death, were documented. Results: After 3 years follow-up, Kaplan-Meier cumulative event rates for MACE were 15.4% in patients with high Lp(a) levels (>137 nmol/L; >80th cohort percentile) and 10.2% in patients with low Lp(a) levels (≤137 nmol/L; ≤80th cohort percentile; log-rank test: P =0.047). Cox regression analyses adjusted for conventional cardiovascular risk factors revealed a significant association between high Lp(a) levels and 3-year MACE with an adjusted hazard ratio of 1.69 (95% CI, 1.07–2.66). One-third of MACE occurred within 30 days after CEA, with an adjusted hazard ratio for the 30-day risk of MACE of 2.05 (95% CI, 1.01–4.17). Kaplan-Meier curves from time point 30 days to 3 years onward revealed no significant association between high Lp(a) levels and MACE. Lp(a) levels were not associated with histological carotid plaque characteristics. Conclusions: High Lp(a) levels (>137 nmol/L; >80th cohort percentile) are associated with an increased risk of 30-day MACE after CEA. This identifies elevated Lp(a) levels as a new potential risk factor for secondary cardiovascular events in patients after carotid surgery. Future studies are required to investigate whether Lp(a) levels might be useful in guiding treatment algorithms for carotid intervention.

Download Full-text

Distinct Characteristics of VEGF‐D and VEGF‐C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease

Journal of the American Heart Association ◽

10.1161/jaha.119.015761 ◽

2020 ◽

Vol 9 (9) ◽

Cited By ~ 2

Author(s):

Hiromichi Wada ◽

Masahiro Suzuki ◽

Morihiro Matsuda ◽

Yoichi Ajiro ◽

Tsuyoshi Shinozaki ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Angiography ◽

Cardiovascular Events ◽

Troponin I ◽

Cardiovascular Death ◽

Major Adverse Cardiovascular Events ◽

All Cause Mortality ◽

Artery Disease ◽

Cardiovascular Biomarkers

Background VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.

Download Full-text

The Impact Of Waist Circumference And Diabetes On Incident Of Cardiovascular Death During 9 Years Of Follow Up In General Population

10.21203/rs.3.rs-1100214/v1 ◽

2021 ◽

Author(s):

Man Li ◽

Shu-xia Wang ◽

Yong-kang Su ◽

Jin Sun ◽

An-hang Zhang ◽

...

Keyword(s):

Waist Circumference ◽

General Population ◽

Regression Models ◽

Prognostic Value ◽

Cox Regression ◽

Cardiovascular Death ◽

Kaplan Meier ◽

Obesity And Diabetes ◽

Increased Risk

Abstract Background: It has been reported that obesity and diabetes are both the risk factors for the development of cardiovascular diseases (CVD). However, recent articles reported that compared with BMI, waist circumference (WC) can better reflect obesity, more closely related to visceral fat tissue which is positively associated with an increased risk of cardiovascular death. Moreover, few studies have both investigated the prognostic value of both WC and diabetes during a long-term follow up. We aimed to investigate whether higher level of WC measurements and diabetes were able to predict cardiovascular mortality in general population.Methods: In this prospective cohort study, a total of 1521 consecutive subjects free of clinical cardiovascular disease were included. The end point was cardiovascular death. The Kaplan-Meier method and Cox regression models were used to evaluate the cumulative risk of outcome at different WC levels with or without diabetes.Results: During a median follow up of 9.2 years, there were 265 patients had the occurrence of cardiovascular death. Kaplan-Meier survival estimates indicated that the patients with higher levels of WC (WC>94cm) coexist with diabetes had significantly increased risk of cardiovascular death (log-rank p＜0.05). After adjustment for potential confounders, multiple COX regression models showed that the incidence of cardiovascular death was significantly higher when patients with high WC coexisted with DM (HR 3.78; 95% CI: 3.35–3.98; p＜0.001).Conclusion: Patients with high WC and diabetes represent a high-risk population for cardiovascular death. WC and diabetes may provide incremental prognostic value beyond traditional risks factors.

Download Full-text

Combination Use of Clopidogrel and Proton Pump Inhibitors Increases Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248416663647 ◽

2016 ◽

Vol 22 (2) ◽

pp. 142-152 ◽

Cited By ~ 16

Author(s):

Qiang Niu ◽

Zhongsu Wang ◽

Yong Zhang ◽

Jiangrong Wang ◽

Pei Zhang ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Combination Therapy ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Cardiovascular Events ◽

Cochrane Library ◽

Major Adverse Cardiovascular Events ◽

Increased Risk ◽

Artery Disease

Background: Published data indicated that combination use of clopidogrel and proton pump inhibitors (PPIs) may increase the incidence of major adverse cardiovascular events (MACEs). This has been a highly controversial topic for years. Design: The present study was performed to evaluate whether combination therapy of clopidogrel and PPIs is associated with increased risk of MACEs than with clopidogrel alone in patients with coronary artery disease. Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted for studies recording the occurrence of MACEs in patients with exposure to concomitant use of clopidogrel and PPIs up to February 2015. Odds ratios (ORs) were combined using a random-effects model. Results: Patients receiving combination therapy with PPIs and clopidogrel were at significantly increased risk of MACEs (OR: 1.42; 95% confidence interval [CI]: 1.30-1.55). Adding a PPI to clopidogrel treatment was associated with a higher rate of MACE occurrence in rapid metabolizers (RMs, *1/*1) of CYP2C19 (OR: 1.42; 95% CI: 1.12-1.81), but there was no obviously increased rate (OR: 1.43; 95% CI: 0.89-2.28) in decreased metabolizers (with 1 or 2 loss-of-function allele). The increased risk of MACEs was similar in 4 classes of PPIs (omeprazole, lansoprazole, esomeprazole, and pantoprazole), but rabeprazole (OR: 1.03; 95% CI: 0.55-1.95) wasn’t. Conclusion: The combination use of clopidogrel and certain types of PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole) increases the risk of MACE in patients with coronary artery disease. Only in the RMs of CYP2C19, PPIs were associated with significantly increased MACE in patients coadministered with clopidogrel.

Download Full-text

Low testosterone is associated with increased risk of major adverse cardiovascular events in smokers with erectile dysfunction

European Heart Journal ◽

10.1093/eurheartj/ehab724.2601 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

N Ioakeimidis ◽

C Georgakopoulos ◽

D Terentes-Printzios ◽

I Dima ◽

V Gardikioti ◽

...

Keyword(s):

Erectile Dysfunction ◽

Cigarette Smoking ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Testosterone Deficiency ◽

Event Free Survival ◽

Free Survival ◽

Kaplan Meier ◽

Increased Risk ◽

Never Smokers

Abstract Purpose Tobacco cigarette smoking and decreased concentrations of testosterone are major risk factors of erectile dysfunction (ED) and independent predictors of cardiovascular disease (CVD). We investigated, whether testosterone deficiency has a complementary predictive value for CVD events in smokers with ED. Methods A cohort of 398 men with ED and without known atherosclerotic CVD (mean age: 55±10 years) were followed for the occurrence of major adverse cardiovascular events (MACE), (CVD death, coronary artery disease, stroke). Total testosterone (TT) levels were measured in all patients. Results Among the study population, 205 (52%) were smokers. During a mean follow-up of 6 years (range: 1–11 years), 30 (7.5%) patients demonstrated a MACE. Baseline TT levels were significantly lower and prevalence of smoking was higher in the CV-event group than the event-free survival group (P<0.01 and P<0.05, respectively). Kaplan–Meier analysis showed that patients with low TT (≤4.0 ng/mL) had a worse prognosis than patients with TT >4.0 ng/mL (log rank: 6.52, P=0.011), and that smokers had a greater risk of adverse events than never smokers (log rank: 4.42, P=0.04). We then stratified all patients into four groups, on the basis of smoking status (current/never smokers) and low or high TT (≤ or >4.0 ng/mL) and cardiac event-free survival curves were constructed by Kaplan–Meier analysis (figure). The event-free rate in smokers with low TT is significantly lower than that of smokers with low TT or never smokers with normal TT (log rank: 11.3, P=0.02). Smokers with low TT had an almost 4-fold higher risk of MACEs compared to never smokers with normal TT (adjusted hazard ratio: 3.91; P=0.030). Conclusion Cigarette smoking combined with low TT concentration is associated with a shorter event-free period compared with either smoking or testosterone deficiency alone. The measurement of testosterone concentration may be useful to further stratify the risk of ED smokers without known CVD. FUNDunding Acknowledgement Type of funding sources: None. Smoking testosterone deficiency and MACE

Download Full-text

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

Diabetes Care ◽

10.2337/dc21-1744 ◽

2022 ◽

Author(s):

Avivit Cahn ◽

Stephen D. Wiviott ◽

Ofri Mosenzon ◽

Erica L. Goodrich ◽

Sabina A. Murphy ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Events ◽

Cox Regression ◽

Cardiovascular Death ◽

Atherosclerotic Cardiovascular Disease ◽

Baseline Hba1c ◽

Renal Outcomes ◽

Increased Risk ◽

Hba1c Levels

OBJECTIVE Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models. RESULTS In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06–1.19], 1.08 [1.04–1.13], and 1.17 [1.11–1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction > 0.05). CONCLUSIONS Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c <7%.

Download Full-text