Total Major Adverse Cardiovascular Events Research Articles

Prognostic Value of GRACE Risk Scores in Patients With Non-ST-Elevation Myocardial Infarction With Non-obstructive Coronary Arteries.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a special type of myocardial infarction (MI). The GRACE risk score is commonly used to predict major adverse cardiovascular events (MACE) in non-ST-elevation myocardial infarction patients, and the suitability of the GRACE risk score for prognostic stratification in patients with MINOCA remains uncertain. This study aimed to investigate whether the GRACE risk score is capable of predicting MACE in MINOCA patients with NSTE. We calculated the GRACE risk score for 340 consecutive MINOCA patients with NSTE. Patients were divided into a low-intermediate risk group (≤ 140, 48.8%) and a high risk group (>140, 51.2%) according to their GRACE risk scores. The clinical characteristics and outcomes of the patients were assessed. Patients in the high risk group tended to be older and to have more comorbidities. At the 1-year follow-up, the rate of cardiac death in the high risk group was significantly higher than that in the low-intermediate-risk group (p = 0.010). There was no significant difference in non-fatal MI, stroke, heart failure, or cardiovascular-related rehospitalization. The incidence of total MACE was significantly higher in patients with high GRACE risk scores than in patients with low GRACE risk scores (p = 0.006). ROC curve analysis showed that the GRACE risk score has moderate value in predicting MACE in NSTE-MINOCA patients. The area under the ROC curve was 0.710 (95% CI 0.625–0.796, P < 0.001). The GRACE risk score provides potentially valuable prognostic information on clinical outcome when applied to MINOCA patients with NSTE.

Severe Periodontal Disease Increases Acute Myocardial Infarction and Stroke: A 10-Year Retrospective Follow-up Study

This study aimed to evaluate the causal association of periodontal disease with acute myocardial infarction (AMI) and stroke, after controlling for various confounders among the Korean population. A retrospective cohort study using the National Health Insurance Service–National Health Screening Cohort (NHIS-HEALS) was performed during 2002 to 2015 (baseline: 2002 to 2005; follow-up: 2006 to 2015) in the Republic of Korea. A total of 298,128 participants with no history of AMI or stroke were followed up for 10 y. AMI and stroke were defined by a diagnosis using the International Classification of Diseases, 10th Revision (ICD-10) guideline. Periodontal condition was classified into 3 groups (healthy, moderate periodontal disease, severe periodontal disease [SPD]) using the combination of ICD codes, treatment codes in the NHIS, and recommendation of periodontal treatment by the dentists in HEALS. Various confounders, such as sociodemographic, behavioral, systemic, and oral health factors, including hypercholesterolemia, were considered. Multivariable Cox regression analysis was applied to estimate adjusted incidence rate ratio (adjusted hazard ratio [aHR]) based on person-year of periodontal condition for AMI, stroke, and nonfatal major adverse cardiovascular events (MACEs) encompassing AMI or stroke controlling for various confounders. Stratified analyses according to age group, sex, and toothbrushing frequency were also performed. After controlling for various confounders, participants with SPD compared with non-SPD participants had a higher incidence by 11% for AMI (aHR, 1.11; 95% confidence interval [CI], 1.02–1.20), by 3.5% for stroke (aHR, 1.035; 95% CI, 1.01–1.07), and by 4.1% for MACEs (aHR, 1.04; 95% CI, 1.01–1.07). The association of SPD with AMI and MACE was highly modified in females and adults aged 40 to 59 y. In the total Korean population, SPD increased total AMI events by 4.3%, total stroke events by 1.4%, and the total MACEs by 1.6%. Our data confirmed that SPD was causally associated with the new events of AMI and stroke.

Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: a post hoc analysis

BackgroundThe Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participantsMethodsWe compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models.ResultsParticipants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82–0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80–0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87–0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82–0.99) p = 0.028].ConclusionsThese findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk.Clinical Trial Registration:https://www.clinicaltrials.gouv. Unique Identifier NCT01394952).

Impact of smoking status on the relationships of growth differentiation factor 15 with mortality and cardiovascular events in patients with suspected or known coronary artery disease: the ANOX study

Abstract Background Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that plays an important role in the regulation of the inflammatory response, growth and cell differentiation. An elevated GDF-15 was found in various conditions including cigarette smoking and stable coronary artery disease (CAD), and it was reported to predict mortality and cardiovascular (CV) events in general population and in patients with established CAD. However, the impact of smoking status on the relationships of GDF-15 with mortality and CV events in patients with suspected or known CAD is unclear. Methods Serum GDF-15 levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict CV events (ANOX) study, and followed up for 3 years. Patients were divided into 3 groups according to the smoking status: current (n=428), past (n=1,035), and never smokers (n=955). The outcomes were total death, CV death, and major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 48 current, 120 past, and 86 never smokers died from any cause, 17 current, 47 past, and 24 never smokers died from CV disease, and 35 current, 80 past, and 50 never smokers developed MACE. After adjustment for established risk factors, GDF-15 levels were significantly associated with total death (hazard ratio [HR] for 1-SD increase, 1.30; 95% confidence interval [CI], 1.03–1.65), but not with CV death (HR, 1.09; 95% CI, 0.69–1.62) or MACE (HR, 0.95; 95% CI, 0.64–1.34) in current smokers; GDF-15 levels were significantly associated with total death (HR, 1.73; 95% CI, 1.46–2.05) and CV death (HR, 1.41; 95% CI, 1.09–1.85), but not with MACE (HR, 1.20; 95% CI, 0.96–1.48) in past smokers; GDF-15 levels were significantly associated with total death (HR, 1.62; 95% CI, 1.32–1.95), CV death (HR, 1.76; 95% CI, 1.22–2.46), and MACE (HR, 1.64; 95% CI, 1.27–2.07) in never smokers. Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of GDF-15 levels further improved the prediction of total death (P&amp;lt;0.001 for continuous net reclassification improvement [NRI], P=0.001 for integrated discrimination improvement [IDI]) and MACE (P&amp;lt;0.001 for NRI, P=0.045 for IDI), but not that of CV death, in never smokers, while it did not significantly improved the prediction of total death, CV death, or MACE either in current or in past smokers. Conclusions The GDF-15 level was independently associated with total death and MACE in never, but not in current or past smokers with suspected or known CAD. The relationships of GDF-15 with mortality and CV events seem to be attenuated by the presence of current and past smoking. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

Baseline, delta, and achieved low-density lipoprotein cholesterol levels and cardiovascular risk in patients on statin therapy: A post-hoc resampling mediation analysis of treating new targets [TNT] trial.

Clinical guidelines for monitoring low-density lipoprotein cholesterol (LDL-C) after statin therapy do not clearly define the clinical roles of baseline LDL-C, ΔLDL-C, and achieved LDL-C according to statin intensity. We performed post-hoc analysis of the Treating to New Target (TNT) study to evaluate individual LDL-C parameters after statin therapy. Primary outcome was the risk for total major adverse cardiovascular events (MACE). We use resampling multilevel mediation analysis to analyze complex relationships among LDL-C parameters based on similar statin intensities. Tertiles for resample A (matched baseline LDL-C; distinct achieved LDL), resample B (matched ΔLDL-C; distinct baseline LDL-C), and resample C (matched achieved LDL-C; distinct ΔLDL-C) were analyzed using Cox proportional hazard ratios. In original data analysis, the incidence of MACE was reduced in those with lower achieved LDL-C in total, low, and high intensity statin users (hazard ratios [HRs]=0.990, 0.992, 0.992; respectively; all P-values<.001). In mediation analysis, resample A showed consistently high incidence for MACE in the middle tertile (HR=1.237; 95% confidential interval [CI]=1.008-1.517; P-value=.041) and highest tertile (HR=1.275; 95% CI=1.021-1.592; P-value=.032) compared to the lowest tertile. However, resamples B and C did not show consistent differences. Similarly, no consistent statistical difference in MACE according to statin intensity. Lower achieved LDL-C decreased MACE in participants with a similar baseline LDL-C after statin therapy. However, the change in absolute values of ΔLDL-C and achieved LDL-C should be interpreted in an individualized manner due to their complex collinearity, and statin intensity should also be taken into consideration.

Prognostic value of fragmented QRS complex in patients with acute myocardial infarction

Several factors and risk stratification tools have been studied to determine the prognosis of acute coronary syndrome. Fragmented QRS (fQRS) is amarker of myocardial scar and its prognostic role has recently been demonstrated. The present study aimed to investigate the association between the presence of fQRS in electrocardiogram and the prognosis of ST-segment elevation and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI). Atotal of 661 patients with myocardial infarction (MI) were enrolled in aretrospective study. Based on the presence of fQRS in admission electrocardiogram, patients were divided into two groups. All patients were followed up for 6months, and all major adverse cardiovascular events (MACE) were recorded. The mean age of patients was 61.3 ± 1.2 years, and 71.7% were male. In the acute phase, the detection rates of regional wall motion abnormality and aortic valve insufficiency were higher in positive fQRS compared to negative fQRS group (p = 0.003). The incidence of total MACE was significantly higher in the positive fQRS compared to the negative fQRS group among all patients and in both STEMI and NSTEMI subgroups (p < 0.001). Based on multivariate analysis, the presence of fQRS and hypertension were the strongest predictors of total MACE at 6‑month follow-up (odds ratio [OR] = 5.929; 95% confidence interval [CI] = 3.620-9.709; p < 0.001 and OR = 2.220; 95% CI = 1.390-3.547; p < 0.001, respectively). Regardless of the type of MI, it was found that the presence of fQRS on admission electrocardiogram can be implemented in risk stratification tools in patients with acute MI.

Bare metal or drug-eluting stent versus drug-coated balloon in non-ST-elevation myocardial infarction: the randomised PEPCAD NSTEMI trial.

Drug-coated balloons (DCB) may avoid stent-associated long-term complications. This trial compared the clinical outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) treated with either DCB or stents. A total of 210 patients with NSTEMI were enrolled in a randomised, controlled, non-inferiority multicentre trial comparing a paclitaxel iopromide-coated DCB with primary stent treatment. The main inclusion criterion was an identifiable culprit lesion without angiographic evidence of large thrombus. The primary endpoint was target lesion failure (TLF; combined clinical endpoint consisting of cardiac or unknown death, reinfarction, and target lesion revascularisation) after nine months. Secondary endpoints included total major adverse cardiovascular events (MACE) and individual clinical endpoints. Mean age was 67±12 years, 67% were male, 62% had multivessel disease, and 31% were diabetics. One hundred and four patients were randomised to DCB, 106 to stent treatment. In the stent group, 56% of patients were treated with BMS, 44% with current-generation DES. In the DCB group, 85% of patients were treated with DCB only whereas 15% underwent additional stent implantation. During a follow-up of 9.2±0.7 months, DCB treatment was non-inferior to stent treatment with a TLF rate of 3.8% versus 6.6% (intention-to-treat, p=0.53). There was no significant difference between BMS and current-generation DES. The total MACE rate was 6.7% for DCB versus 14.2% for stent treatment (p=0.11), and 5.9% versus 14.4% in the per protocol analysis (p=0.056), respectively. In patients with NSTEMI, treatment of coronary de novo lesions with DCB was non-inferior to stenting with BMS or DES. These data warrant further investigation of DCB in this setting, in larger trials with DES as comparator (ClinicalTrials.gov Identifier: NCT01489449).

Roles of Achieved Levels of Low-Density Lipoprotein Cholesterol and High-Sensitivity C-Reactive Protein on Cardiovascular Outcome in Statin Therapy

In statin therapy, the prognostic role of achieved low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) in cardiovascular outcomes has not been fully elucidated. A total of 4,803 percutaneous coronary intervention (PCI)-naïve patients who prescribed moderate intensity of statin therapy were followed up. Total and each component of major adverse cardiovascular events (MACE) according to LDL-C and hsCRP quartiles were compared. The incidence of 5-year total MACEs in the highest quartile group according to the followed-up hsCRP was higher than that in the lowest quartile (hazard ratio (HR) = 2.16, p < 0.001). However, there was no difference between the highest and lowest quartiles of the achieved LDL-C (HR = 0.95, p = 0.743). After adjustment of potential confounders, the incidence of total death, de novo PCI, atrial fibrillation, and heart failure in the highest quartile of followed-up hsCRP, was higher than that in the lowest quartile (all p < 0.05). However, other components except for de novo PCI in the highest quartile by achieved LDL-C was not different to that in the lowest quartile. These results suggest that followed-up hsCRP can be more useful for predicting future cardiovascular outcome than achieved LDL-C in PCI-naïve patients with statin therapy.

Occurence of First and Recurrent Major Adverse Cardiovascular Events With Liraglutide Treatment Among Patients With Type 2 Diabetes and High Risk of Cardiovascular Events

After the occurrence of nonfatal cardiovascular events, recurrent events are highly likely. Most cardiovascular outcomes trials analyze first events only; extending analyses to first and recurrent (total) events can provide clinically meaningful information. To investigate whether liraglutide is associated with reduced first and recurrent total major adverse cardiovascular events (MACE) compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events. This post hoc analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) randomized, double-blind, clinical trial included data from patients with type 2 diabetes who had established or were at high risk for cardiovascular disease at 410 sites in 32 countries from August 2010, to December 2015. Data analysis was performed from August 15, 2016, to July 5, 2019. Patients were randomized 1:1 to receive liraglutide (up to 1.8 mg per day) or placebo, both with standard care, for 3.5 to 5.0 years. Assessed outcomes were MACE (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), expanded MACE (primary MACE plus coronary revascularization and hospitalization for heart failure or unstable angina pectoris), and the individual end points. The 9340 LEADER trial participants (6003 [64.3%] male; mean [SD] age, 64.3 [7.2] years) experienced 1605 total MACE (1302 first and 303 recurrent events; median follow-up, 3.8 years [range, 0-5.2 years]). Patients who experienced any MACE were older (1 MACE: mean [SD] age, 65.6 [8.0] years; >1 MACE: 65.7 [7.9] years) and had diabetes for longer duration (1 MACE: mean [SD] duration, 13.4 [8.3] years; >1 MACE: 14.4 [8.7] years) compared with patients without MACE (mean [SD] age, 64.1 [7.1] years; mean [SD] duration, 12.7 [7.9] years). Fewer first and recurrent MACE occurred in the liraglutide group (n = 4668; 608 first and 127 recurrent events) than in the placebo group (n = 4672; 694 first and 176 recurrent events). Liraglutide was associated with a 15.7% relative risk reduction in total MACE (hazard ratio [HR], 0.84; 95% CI, 0.76-0.93) and a 13.4% reduction in total expanded MACE (HR, 0.87; 95% CI, 0.81-0.93) compared with placebo. For most individual cardiovascular end points, liraglutide was associated with lower risk vs placebo. These results suggest that liraglutide treatment is associated with reduced total MACE compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events. This analysis supports the findings of an absolute benefit of liraglutide treatment with respect to the overall burden of cardiovascular events in this high-risk patient population. ClinicalTrials.gov identifier: NCT01179048.

4098Reduced skeletal muscle mass is associated to worsened long-term clinical outcomes in patients with coronary artery disease: a quantitative analysis by computed tomography

Abstract Background Sarcopenia is closely associated to poor clinical outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). However, it is unclear whether the skeletal muscle mass at baseline has quantitative effect on future cardiovascular outcomes. Purpose We investigated the quantitative effect of skeletal muscle mass on future cardiovascular outcomes in patients with coronary artery disease (CAD). Methods Total 475 patients those who underwent successful percutaneous coronary intervention (PCI) for CAD and performed computed tomography (CT) scan within 30 days of PCI were enrolled. The cross-sectional area of skeletal muscle at the first lumbar vertebra (L1) level was measured. Whole study population was divided into 4 groups according to the sex-specific quartiles of skeletal muscle index (SMI). Primary outcome was all-cause mortality and secondary outcome was major adverse cardiovascular event (MACE) within 3 years of follow-up. Results Mean follow-up duration was 4.11±3.02 years and average time period from the date of PCI to CT scan was −3.33±11.72 days. The incidence of 3-year all-cause mortality (23.2% vs. 9.9% vs. 6.6% vs. 4.4%, p&lt;0.001) and MACE (42.9% vs. 24.0% vs. 14.3% vs. 6.2%, p&lt;0.001) was significantly higher in the group of lower quartiles of L1-SMI. In the fully adjusted multivariable analysis, lower quartiles of L1-SMI was an independent predictor of higher risk of all-cause mortality and MACE (lowest vs. highest quartile; OR: 4.90, 95% CI: 1.54 to 15.5, p=0.007; and OR: 12.3, 95% CI: 4.99 to 30.4, p&lt;0.001, respectively). Results of 3-year clinical outcomes SMI Q1 (n=124) SMI Q2 (n=116) SMI Q3 (n=112) SMI Q4 (n=123) Log-rank p-value All-cause mortality 27 (23.2) 11 (9.9) 7 (6.6) 5 (4.4) &lt;0.001 Non-fatal MI 9 (8.7) 3 (3.0) 2 (2.0) 3 (2.6) 0.038 Repeat revascularization 20 (24.9) 15 (15.2) 7 (7.1) 4 (3.8) &lt;0.001 Total MACEs 47 (42.9) 26 (24.0) 15 (14.3) 7 (6.2) &lt;0.001 Data are expressed as n (%). MACE = major adverse cardiovascular event; MI = myocardial infarction; SMI = skeletal muscle index; Q = quartile. Impact of reduced skeletal muscle on CAD Conclusion Skeletal muscle mass at baseline is a powerful predictor of future adverse clinical outcomes in patients with CAD undergoing successful PCI. Quantitative assessment of skeletal muscle mass at L1 level by CT scan provides prognostic implication for future cardiovascular risk stratification. Acknowledgement/Funding National Research Foundation of Korea (NRF-2016R1A2B3013825), Ministry of Future Creation and Science of Korea (2018K000255)

Serum concentration of full-length- and carboxy-terminal fragments of endothelial lipase predicts future cardiovascular risks in patients with coronary artery disease

Endothelial lipase (EL), a regulator of plasma high-density lipoprotein cholesterol (HDL-C), is secreted as a 68-kDa mature glycoprotein, and then cleaved by proprotein convertases. However, the clinical significance of the circulating EL fragments remains unclear. The objective of this study was to analyze the impact of serum EL fragments on HDL-C levels and major adverse cardiovascular events (MACE). Using novel monoclonal antibodies (RC3A6) against carboxy-terminal EL protein, we have established a new enzyme-linked immunosorbent assay (ELISA) system, which can detect both full-length EL protein (full EL) and carboxy-terminal truncated fragments (total EL) in serum. The previous sandwich ELISA detected only full EL. The full and total EL mass were measured in 556 patients with coronary artery disease. Among them, 272 patients who underwent coronary intervention were monitored for 2years for MACE. There was a significant correlation between serum full and total EL mass (R=0.45, P<.0001). However, the total EL mass showed a stronger inverse correlation with serum HDL-cholesterol concentration than the full EL mass (R=-0.17 vs -0.02). Kaplan-Meier analysis documented an association of serum total EL mass and MACE (log-rank P=.037). When an optimal cutoff value was set at 96.23ng/mL, total EL mass was an independent prognostic factor for MACE in the Cox proportional hazard model (HR; 1.75, 95% CI; 1.10-2.79, P=.018). Serum total EL mass could be a predictor for MACE in patients with coronary artery disease. This novel ELISA will be useful for further clarifying the impact of EL on HDL metabolism and atherosclerosis.

Cardiovascular events associated with nicorandil administration prior to primary percutaneous coronary intervention in patients with acute ST-segment elevated myocardial infarction: a systematic review and meta-analysis

ABSTRACTIntroduction: Nicorandil may exert cardioprotective effects in ischemic heart disease. However, its efficacy in combination with early reperfusion is uncertain. The authors performed a meta-analysis of the short- and long-term clinical outcomes of nicorandil administration at the time of primary percutaneous coronary intervention (PCI) in patients with ST-elevated myocardial infarction (STEMI).Methods: PubMed, MEDLINE, Embase, and the Cochrane Library databases were systematically searched for eligible randomized controlled studies. The primary endpoint was major adverse cardiovascular events (MACE), both in-hospital and post-discharge. The secondary endpoint was the incidence of no-reflow phenomenon.Results: Ten studies were included (n = 1105). Mean patient age was 63.0 ± 10.0 years; 76.6% of patients were male. Compared with controls who received primary PCI, combined nicorandil/primary PCI significantly reduced in-hospital MACE (pooled odds ratio [OR] 0.16; 95% confidence interval [CI] 0.09–0.27), follow-up MACE (pooled OR 0.53; 95% CI 0.37–0.75), and total MACE (pooled OR 0.27; 95% CI 0.15–0.49). The combined treatment also reduced the incidence of no-reflow phenomenon (pooled OR 0.34; 95% CI 0.23–0.50).Conclusion: Nicorandil administration at the time of primary PCI is associated with reduced MACE (both short- and long-term) and no-reflow phenomenon in patients with STEMI.

Impact of diabetes mellitus on 5-year clinical outcomes in patients with chronic total occlusion lesions.

Diabetes mellitus (DM) is a major predictor of cardiovascular morbidity and mortality. However, there are limited data on the impact of DM in patients who have chronic total occlusion (CTO) lesion on long-term outcomes. A total of 822 CTO patients who underwent coronary angiography, treated by either percutaneous coronary intervention or optimal medical therapy, were enrolled and divided into two groups: (i) diabetic group (n=363) and (ii) nondiabetic group (n=459). Individual and composite major clinical outcomes were compared up to 5 years. Propensity score matching analysis was carried out generating two groups (298 pairs, n=596, C-statistic=0.655) with balanced baseline characteristics. Up to 5 years, the DM group showed a higher trend toward revascularization (19.5 vs. 13.5%, P=0.051) and major adverse cardiovascular events (MACE) (24.7 vs. 19.1%, P=0.097) compared with the nondiabetic group. However, there was no difference in the incidence of death and myocardial infarction between the two groups. Subgroup analysis showed that the chronic kidney disease (CKD) subgroup was associated with a higher incidence of all-cause death, cardiac death, myocardial infarction, revascularization, and MACE in comparison with diabetic patients without CKD and nondiabetic patients, respectively (total MACE: 39 vs. 20.5 vs. 19.2% , P=0.001). Insulin-dependent diabetic patients had a significantly higher incidence of MACE (hazard ratio=1.58; 95% confidence interval: 1.04-2.40; P=0.03) compared with the nondiabetic patients. Diabetic patients with CTO were associated with a trend toward a higher incidence of revascularization and total MACE up to 5 years. Insulin-dependent and diabetic patients with CKD subgroups had a significantly higher incidence of total MACE.

Usefulness of Carotid Plaques as Predictors of Obstructive Coronary Artery Disease and Cardiovascular Events in Asymptomatic Individuals With Diabetes Mellitus

Carotid intima-media thickness (CIMT) measurement and carotid plaque detection by B-mode ultrasound are frequently used as surrogates to predict coronary artery disease (CAD). However, their systematic use in routine clinical management of asymptomatic patients with diabetes mellitus (DM) has not been studied. The aim of the study was to identify carotid parameters that predict cardiovascular events in patients with asymptomatic type 2 DM by evaluating the relation between carotid disease and CAD. This multicenter, observational, prospective study included 259 asymptomatic patients with type 2 DM followed-up for 34 months after measurement of CIMT and carotid plaque with carotid ultrasound, and CAD assessment with computed tomography coronary angiography. Statistically significant differences between patients with and without carotid plaque were found for coronary plaque >50% stenosis (59 vs 36, p = 0.02). Greater maximal CIMT was associated with an increased risk of coronary plaque >50% (odds ratio 1.21 [1.02, 1.44], p = 0.03) and >70% stenosis (odds ratio 1.23 [1.01, 1.50], p = 0.04) after adjusting for traditional risk factors. At 34-month follow-up, the occurrence of total major adverse cardiovascular event was estimated to be 7.1% (mean age 68 years, 6% male and 1.1% female) in the whole study population. The subgroup of patients with carotid plaque showed increased incidence of major adverse cardiovascular event compared with patients with no carotid plaque (p = 0.005). In conclusion, carotid plaque was a strong predictor of future cardiovascular events and may be a prognostic marker in asymptomatic patients with type 2 DM. Carotid plaque and maximal intima-media thickness were independently associated with obstructive CAD.

Six months outcome in patients undergoing percutaneous coronary intervention for true bifurcation lesions without side branch stenting

Context: Bifurcation lesions is one of the most challenging lesions in interventional cardiology. The optimal management is still a debate. Provisional stenting is preferred approach at present, yet with higher major adverse cardiovascular events (MACE) than other lesions. Aims: The aim of this study is to evaluate outcome in patients with true coronary bifurcation lesion undergoing percutaneous coronary intervention with stenting of the main vessel without side branch (SB) intervention. Design: This was prospective observational study. Subjects and Methods: The study was conducted in patients with stable angina or unstable angina or non ST elevation MI (NSTEMI) attributable to a de novo true coronary bifurcation lesion involving the main vessel and SB. The main vessel diameter has to be ≥≥2.5 mm and the SB has to be ≥≥2.25 mm by visual estimate. Statistical Analysis: Statistical analysis was performed using statistical software package SPSS v22.0. Results: Fifty-three consecutive patients of true bifurcation lesions were studied. They underwent main vessel stenting and were followed up for 6 months. Mean age of 54.9 ± 8.4 was studied, 66% were male, 45.3% were single-vessel disease, left anterior descending (LAD)-diagonal was the most common (43.4%) target bifurcation lesion, most common medina class was 1,1,1 (43.4%). On 6 months follow-up, total MACE events were 12 (22.6%), most were contributed by Target lesion revascularization (TLR) 11 (20.75%). The MACE were significantly associated with diabetes and the extend of coronary artery disease.. Conclusions: Simple stenting strategy in true bifurcation lesions is associated with high MACE events. Further studies dedicated to true coronary bifurcation lesions are required to look for best strategy for these lesions.

Moderate-intensity statin therapy seems ineffective in primary cardiovascular prevention in patients with type 2 diabetes complicated by nephropathy. A multicenter prospective 8years follow up study.

BackgroundAlthough numerous studies and metanalysis have shown the beneficial effect of statin therapy in CVD secondary prevention, there is still controversy such the use of statins for primary CVD prevention in patients with DM. The purpose of this study was to evaluate the occurrence of total major adverse cardio-vascular events (MACE) in a cohort of patients with type 2 diabetes complicated by nephropathy treated with statins, in order to verify real life effect of statin on CVD primary prevention.MethodsWe conducted an observational prospective multicenter study on 564 patients with type 2 diabetic nephropathy free of cardiovascular disease attending 21 national outpatient diabetes clinics and followed them up for 8 years. 169 of them were treated with statins (group A) while 395 were not on statins (group B).ResultsNotably, none of the patients was treated with a high-intensity statin therapy according to last ADA position statement. Total MACE occurred in 32 patients from group A and in 68 patients from group B. Fatal MACE occurred in 13 patients from group A and in 30 from group B; nonfatal MACE occurred in 19 patients from group A and in 38 patients from group B. The analysis of the Kaplan–Meier survival curves showed a not statistically significant difference in the incidence of total (p 0.758), fatal (p 0.474) and nonfatal (p 0.812) MACE between the two groups. HbA1c only showed a significant difference in the incidence of MACE between the two groups (HR 1.201, CI 1.041–1.387, p 0.012).ConclusionsThese findings suggest that, in a real clinical setting, moderate-intensity statin treatment is ineffective in cardiovascular primary prevention for patients with diabetic nephropathy. Trial registration ClinicalTrials.gov Identifier NCT00535925. Date of registration: September 24, 2007, retrospectively registered

Impact of Renin-Angiotensin System Inhibitors on Long-Term Clinical Outcomes of Patients With Coronary Artery Spasm.

BackgroundCoronary artery spasm (CAS) is a well‐known endothelial dysfunction, and a major cause of vasospastic angina (VSA). The renin–angiotensin system (RAS) is known to be closely associated with endothelial function. However, there are only a few studies that investigated the impact of RAS inhibitor on long‐term clinical outcomes in VSA patients.Methods and ResultsA total of 3349 patients with no significant coronary artery disease, diagnosed with CAS by acetylcholine provocation test were enrolled for this study. Significant CAS was defined as having ≥70% narrowing of the artery after incremental injections of 20, 50, and 100 μg of acetylcholine into the left coronary artery. Patients were divided into 2 groups according to whether the prescription included RAS inhibitor or not (RAS inhibitor group: n=666, non‐RAS inhibitor group; n=2683). To adjust for any potential confounders that could cause bias, propensity score matching (PSM) analysis was performed using a logistic regression model. After PSM analysis, 2 matched groups (524 pairs, n=1048 patients, C‐statistic=0.845) were generated and their baseline characteristics were balanced. During the 5‐year clinical follow‐up, the RAS inhibitor group showed a lower incidence of recurrent angina (8.7% versus 14.1%, P=0.027), total death (0.0% versus 1.3%, P=0.045), and total major adverse cardiovascular events (1.0% versus 4.1%, P=0.026) than the non‐RAS inhibitor group.ConclusionsChronic RAS inhibitor therapy was associated with lower incidence of cardiovascular events in VSA patients in the 5‐year clinical follow‐up.

Effect of intracoronary tirofiban bolus administration on platelet-derived microparticles and short-term clinical benefit in patients with acute ST-segment elevation myocardial infarction

Objective To investigate the effect of intracoronary tirofiban bolus administration on platelet-derived microparticles (PMPs) and its correlation with the short-term clinical benefit in patients with acute ST-segment elevation myocardial infarction (ASTEMI) undergoing emergency percutaneous coronary intervention (PCI). Methods A total of 90 patients with ASTEMI undergoing emergency PCI were selected and randomized into the intracoronary group (intracoronary tirofiban 10.00 μg/kg bolus within 1-3 min followed by intravenous continuous infusion at 0.15 μg·kg-1·min-1 for 36 h, n=30), intravenous group (intravenous tirofiban 10.00 μg/kg bolus within 1-3 min followed by intravenous continuous infusion at 0.15 μg·kg-1·min-1 for 36 h, n=30) and control group (without tirofiban administration, n=30). The 3 ml blood samples from coronary artery were obtained before and 10 min after tirofiban infusion. The 3 ml blood samples from radial artery were collected 24 hours after tirofiban infusion and 12 hours after drug withdrawal. The counts of PMPs were analyzed by flow cytometry. The thrombolysis in myocardial infarction (TIMI) flow grade classification and TIMI Myocardial Perfusion Grade in the culprit blood vessel after PCI, and the incidences of bleeding and major adverse cardiac events (MACE) within 30 days after surgery were recorded. Results There was no significant difference in baseline of PMPs among intracoronary group, intravenous group and control group (all P>0.05). The level of PMPs was decreased in the intracoronary and intravenous group as compared with the control group 〔(3.6±2.3)%, (5.1±2.7)% vs. (6.7±3.2)%, P 0.05), and PMPs levels were lower in intracoronary and intravenous group than in control group (both P 0.05). Immediately after PCI, the TIMI flow grade and TIMI myocardial perfusion grade in the culprit blood vessel in intracoronary group were superior to those in the intravenous group and control group (P 0.05). Conclusions The intracoronary versus intravenous tirofiban administration can effectively and immediately reduce the number of PMPs in patients with acute ST-segment elevation myocardial infarction undergoing emergency interventional treatment, quickly inhibit the activated platelets, and decrease the total major adverse cardiovascular events without increasing the risk of bleeding. Key words: Myocardial infarction; Blood platelets; Angioplasty, intervention, percutaneous coronary

Abstract 16401: Cardiovascular Clinical Effects of Testosterone Supplementation Among Healthy Hypo-androgenic Men: Information From the Intermountain Healthcare Health Plans Database

Introduction: Epidemiologic studies have identified low serum testosterone (T) levels as an independent risk factor for cardiovascular (CV) and total mortality. However, the cardiovascular safety of T therapy among healthy men with low T levels is unknown. Hypothesis: We hypothesized that T supplementation among healthy men over the age of 50 yrs with low T levels is not associated with an increased risk of major adverse cardiovascular events (MACE). Methods: All men in the Intermountain Healthcare Health Plans Database &gt;50 years of age, with no prior history of CV disease, a documented low (&lt;212 ng/dL) baseline T level, at least 1 follow-up (f/u) T level and 3 years of clinical f/u were stratified by whether or not they received at least 90 days of T supplementation (topical gel or injection) or not. Cox hazard regression analysis, adjusting for 17 baseline variables, was performed to determine any association between T supplementation and 3 year MACE (death [D], non-fatal MI, and stroke). Results: A total of 1,472 men (age 57.0 ± 5.5 y, diabetes: 20%, hypertension: 41%, hyperlipidemia: 43%, smokers: 13%) were studied. Event rates at 1 and 3-y by supplementation status, and adjusted HRs, are shown in the Table. Overall 3-y rates of MACE, D, MI and stroke were low consistent with the baseline age and health of the population. After adjustment, subjects supplemented with T had statistically reduced 1 and 3 year rates of D and total MACE, including numerically reduced rates of MI and stroke compared to those receiving no supplementation. Conclusions: Among a generally healthy and relatively young population of hypo-androgenic men, T therapy was associated with reduced MACE and D over 3-y compared to no T supplementation. These findings provide further observational evidence of the CV safety associated with T supplementation in this population.

Carotid plaque calcification predicts future cardiovascular events in type 2 diabetes.

The presence of carotid plaques is associated with future cardiovascular events, with local plaque composition being an independent outcome predictor. We examined the association between ultrasonographically determined carotid plaque calcification and incident major adverse cardiovascular events (MACE) and death in type 2 diabetes (T2D). We enrolled 581 patients with T2D who underwent routine carotid ultrasonography. Plaques were classified as echolucent (lipid rich), heterogenous, and echogenic (calcific). We collected demographic, anthropometric, and clinical data at baseline and followed the patients for up to 9 years. Plaques were detected in 81.8% of the patients (echolucent in 16.4%, heterogenous in 43.2%, and echogenic in 22.2%). During follow-up (4.3 ± 0.1 years), 58 deaths (27 cardiovascular) and 236 fatal and nonfatal MACE occurred. In univariate analyses, presence versus absence of any carotid plaque was associated with incident MACE, and the hazard ratio (95% CI) progressively increased from echolucent (1.97 [0.93-3.44]), to heterogeneous (3.10 [2.09-4.23]), to echogenic (3.71 [2.09-5.59]) plaques. Compared with echolucent plaques, echogenic plaques were associated with incident MACE independently from confounders. This association was attenuated after adjusting for the degree of stenosis, but in patients with stenosis ≤30%, echogenic plaque type still predicted total and atherosclerotic MACE, even after further adjusting for mean intima-media thickness. In T2D, carotid plaque calcification predicts MACE, especially in patients with a low degree of stenosis. The biology of atherosclerotic calcification in diabetes needs to be further elucidated to understand the basis of this association.