Effects of the stress hyperglycemia ratio on long-term mortality in patients with triple-vessel disease and acute coronary syndrome.

AIMS: Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). METHODS: A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. RESULTS: During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160-2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. CONCLUSIONS: The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Implications of left atrial volume index in patients with three-vessel coronary disease: A 6.6-year follow-up cohort study.

BACKGROUND: Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD. METHODS: This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. RESULTS: During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). CONCLUSIONS: LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

An elevated triglyceride-glucose index predicts adverse outcomes and interacts with the treatment strategy in patients with three-vessel disease.

BACKGROUND: Insulin resistance is a pivotal risk factor for cardiovascular diseases, and the triglyceride-glucose (TyG) index is a well-established surrogate of insulin resistance. This study aimed to investigate the prognostic value of the TyG index and its ability in therapy guidance in patients with three-vessel disease (TVD). METHODS: A total of 8862 patients with TVD with available baseline TyG index data were included in the study. The endpoint was major adverse cardiac events (MACE). All patients received coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy (MT) alone reasonably. RESULTS: An elevated TyG index was defined as the TyG index greater than 9.51. During a median follow-up of 7.5 years, an elevated TyG index was significantly associated with an increased risk of MACE (adjusted hazard ratio 1.161, 95% confidence interval 1.026-1.314, p = 0.018). The elevated TyG index was shown to have a more pronounced predictive value for MACE in patients with diabetes, but failed to predict MACE among those without diabetes, whether they presented with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Meanwhile, the association between an elevated TyG index and MACE was also found in patients with left main involvement. Notably, CABG conferred a significant survival advantage over PCI in patients with a normal TyG index, but was not observed to be superior to PCI in patients with an elevated TyG index unless the patients had both ACS and diabetes. In addition, the benefit was shown to be similar between MT and revascularisation among patients with SAP and an elevated TyG index. CONCLUSIONS: The TyG index is a potential indicator for risk stratification and therapeutic decision-making in patients with TVD.

Mild Renal Function Impairment and Long-Term Outcomes in Patients with Three-Vessel Coronary Artery Disease: A Cohort Study.

INTRODUCTION: Limited data are available on the long-term impact of mild renal dysfunction (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1.73 m2) in patients with three-vessel coronary disease (3VD). METHODS: A total of 5,272 patients with 3VD undergoing revascularization were included and were categorized into 3 groups: normal renal function (eGFR ≥90 mL/min/1.73 m2, n = 2,352), mild renal dysfunction (eGFR 60-89, n = 2,501), and moderate renal dysfunction (eGFR 30-59, n = 419). Primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. RESULTS: During the median 7.6-year follow-up period, 555 (10.5%) deaths occurred. After multivariable adjustment, patients with mild and moderate renal dysfunction had significantly higher risks of all-cause death (adjusted hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.07-1.70; adjusted HR: 2.06, 95% CI: 1.53-2.78, respectively) compared with patients with normal renal function. Patients after coronary artery bypass grafting (CABG) had a lower rate of all-cause death and MACCE than those undergoing percutaneous coronary intervention (PCI) in the normal and mild renal dysfunction group but not in the moderate renal dysfunction group. Results were similar after propensity score matching. CONCLUSIONS: In patients with 3VD, even mild renal impairment was significantly associated with a higher risk of all-cause death. The superiority of CABG over PCI diminished in those with moderate renal dysfunction. Our study alerts clinicians to the early screening of mild renal impairment in patients with 3VD and provides real-world evidence on the optimal revascularization strategy in patients with renal impairment.

HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.

BACKGROUND: To investigate the association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk (RCR) in patients with premature triple-vessel disease (PTVD). METHODS: Three SNPs within HMGCR including rs12916, rs2303151, and rs4629571, and four SNPs within NPC1L1 including rs11763759, rs4720470, rs2072183, and rs2073547 were genotyped. RCR was defined as achieved low-density lipoprotein cholesterol (LDL-C) concentrations after statins higher than 1.8 mmol/L (70 mg/dL). RESULTS: Finally, a total of 609 PTVD patients treated with moderate-intensity statins were included who were divided into two groups: non-RCR group (n = 88) and RCR group (n = 521) according to LDL-C concentrations. Multivariate logistic regression showed the homozygotes for the minor allele of rs12916 within HMGCR gene (CC) were associated with a 2.08 times higher risk of RCR in recessive model [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.16-3.75]. In codominant model, the individuals homozygous for the minor allele of rs12916 (CC) were associated with a 2.26 times higher risk of RCR (OR: 2.26, 95% CI: 1.16-4.43) while the heterozygous individuals (CT) were not, compared with the individuals homozygous for the major allele of rs12916 (TT). There was no significant association between the SNPs within NPC1L1 gene and RCR in various models. CONCLUSIONS: We first reported that the variant homozygous CC of rs12916 within HMGCR gene may incur a significantly higher risk of RCR in PTVD patients treated with statins, providing new insights into early individualized guidance of precise lipid-lowering treatment.

Cardiac index: A superior parameter of cardiac function than left ventricular ejection fraction in risk stratification of hypertrophic cardiomyopathy.

BACKGROUND: An appropriate indicator of cardiac function in the risk stratification of hypertrophic cardiomyopathy (HCM) patients is urgently needed. Cardiac index that reflects cardiac pumping function may be suitable. OBJECTIVE: The purpose of this study was to investigate the clinical significance of reduced cardiac index in HCM patients. METHODS: A total of 927 HCM patients were enrolled. The primary endpoint was cardiovascular death. The secondary endpoints were sudden cardiac death (SCD) and all-cause death. Combination models were constructed by adding reduced cardiac index and reduced left ventricular ejection fraction (LVEF) to the HCM risk-SCD model. Predictive accuracy was determined by C-statistics. RESULTS: Reduced cardiac index was defined as cardiac index ≤2.42 L/min/m2. During median follow-up of 4.3 years, 51 patients reached the endpoint. Reduced cardiac index independently increased the risk of cardiovascular death (adjusted hazard ratio [aHR] 2.976; P = .007), SCD (aHR 6.385; P = .001), and all-cause death (aHR 2.428; P = .010). By adding reduced cardiac index to the HCM risk-SCD model, the model C-statistic increased from 0.691 to 0.762, with an integrated discrimination improvement of 0.021 (P = .018) and a net reclassification improvement of 0.560 (P = .007). The addition of reduced LVEF failed to improve the original model. Better predictive accuracy for all endpoints was also indicated in reduced cardiac index than in reduced LVEF. CONCLUSION: Reduced cardiac index is an independent predictor of poor prognoses in HCM patients. Combining reduced cardiac index rather than reduced LVEF improved the HCM risk-SCD stratification strategy. The reduced cardiac index showed better predictive accuracy than reduced LVEF for all endpoints.

Machine learning improves mortality prediction in three-vessel disease.

BACKGROUND AND AIMS: Risk stratification for three-vessel coronary artery disease (3VD) remains an important clinical challenge. In this study, we utilized machine learning (ML), which can address the limitations of traditional regression-based models, to develop a novel model to assess mortality risk in patients with 3VD. METHODS: This study was based on a prospective cohort of 8943 participants with 3VD consecutively enrolled between 2004 and 2011. An ML-derived random forest model was trained and tested to predict 4-year mortality. The predictability of the model was compared with that of an established model, the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score II (SSII), among 3VD patients undergoing percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT) alone. RESULTS: The all-cause mortality was 7.5% (667 patients) over the 4-year follow-up period. The correlation-based feature selection algorithm selected 18 of the 94 features to develop the ML model. In the testing dataset, the ML-derived model achieved an area under the curve of 0.81 for 4-year mortality prediction. Its predictability was significantly better than that of the SSII among patients undergoing PCI (0.80 vs. 0.70, p < 0.001) or CABG (0.80 vs. 0.67, p < 0.001). The model also outperformed the SSII in patients receiving MT alone (ML: 0.75 vs. SSII for PCI: 0.70 or SSII for CABG: 0.66, p < 0.001). CONCLUSIONS: This ML-based approach exhibited better performance in risk stratification for 3VD compared with the conventional method. Further validation studies are needed to confirm these findings.

Long-term outcome of percutaneous or surgical revascularization with and without prior stroke in patients with three-vessel disease.

OBJECTIVE: To determine whether high-risk patients with three-vessel disease (TVD) with and without prior stroke preferentially benefit from three strategies [percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical therapy (MT)]. METHODS: A total of 8943 patients with TVD were included in the study. Patients enrolled were stratified into two categories according to the presence or absence of prior stroke history. The primary endpoint was all-cause death. Secondary endpoints included stroke and major adverse cardiac and cerebrovascular event (MACCE), a composite of death, myocardial infarction (MI), unplanned revascularization and stroke. RESULTS: Prior stroke was present in 888 patients (9.9%). These patients were older and had higher rates of comorbidities. During a median follow-up of 7.5 years, patients with prior stroke were strongly associated with increased risks of all-cause death, cardiac death, stroke and MACCE, even after adjusting for confounding variables and results been consistent across either treatment subgroup (PCI, CABG and MT) (all adjusted P < 0.01). Notably, there was a significant interaction between prior stroke history and treatment strategies. Revascularization strategy (PCI or CABG) was associated with a lower incidence of all-cause death and MACCE compared with MT alone, and favorable rates of MACCE, MI and unplanned revascularization in the CABG group compared with the PCI group, but with similar rate of all-cause death regardless of prior stroke history. The prevalence of stroke was significantly higher after CABG when compared with PCI or MT in no prior stroke patients [hazard ratio (HR) = 1.429, 95% CI: 1.132-1.805 for CABG vs. MT; HR = 1.703, 95% CI: 1.371-2.116 for CABG vs. PCI]. CONCLUSIONS: Patients with TVD and prior stroke have poor clinical outcomes. It is essential to balance benefit and risk when determining the optimal treatment strategy for TVD with and without prior stroke.

Novel polymorphism of the HMGCR gene related to the risk of diabetes in premature triple-vessel disease patients.

BACKGROUND: Coronary heart disease and diabetes are highly interrelated and complex diseases. We proposed to investigate the association of genetic polymorphisms of the lipoprotein important regulatory genes Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with premature triple-vessel coronary disease (PTVD) with diabetes, blood glucose and body mass index. METHODS: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183 and rs2073547) of NPC1L1 and three SNPs (rs12916, rs2303151 and rs4629571) of HMGCR were genotyped in 872 PTVD patients. RESULTS: After performing logistic regression analysis adjusted for age and sex, rs2303151 of HMGCR was related to the risk of diabetes in the dominance model (odds ratio = 1.35, 95% confidence interval = 1.01-1.80, p = 0.04). However, the four SNPs of NPC1L1 were not associated with the risk of diabetes. Further analyses showed that neither the above SNPs of NPC1L1, nor the SNPs of HMGCR were related to blood glucose and body mass index (all p > 0.05). CONCLUSIONS: We report that rs2303151 is a novel polymorphism of the HMGCR gene related to the risk of diabetes in PTVD patients, which suggests HMGCR may be a potential common targeted pathogenic pathways between coronary heart disease and diabetes.

Using machine learning to aid treatment decision and risk assessment for severe three-vessel coronary artery disease.

BACKGROUND: Three-vessel disease (TVD) with a SYNergy between PCI with TAXus and cardiac surgery (SYNTAX) score of ≥ 23 is one of the most severe types of coronary artery disease. We aimed to take advantage of machine learning to help in decision-making and prognostic evaluation in such patients. METHODS: We analyzed 3786 patients who had TVD with a SYNTAX score of ≥ 23, had no history of previous revascularization, and underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) after enrollment. The patients were randomly assigned to a training group and testing group. The C4.5 decision tree algorithm was applied in the training group, and all-cause death after a median follow-up of 6.6 years was regarded as the class label. RESULTS: The decision tree algorithm selected age and left ventricular end-diastolic diameter (LVEDD) as splitting features and divided the patients into three subgroups: subgroup 1 (age of ≤ 67 years and LVEDD of ≤ 53 mm), subgroup 2 (age of ≤ 67 years and LVEDD of > 53 mm), and subgroup 3 (age of > 67 years). PCI conferred a patient survival benefit over CABG in subgroup 2. There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data. Among the total study population, the multivariable analysis revealed significant differences in the risk of all-cause death among patients in three subgroups. CONCLUSIONS: The combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD. The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.

Interaction Between Treatment and Age or Sex in Non-ST-Segment Elevation Acute Coronary Disease and Three-Vessel Disease.

Aims: To explore the effects of age and sex on the outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with the three-vessel disease (TVD). Methods and Results: The study is a subanalysis of data from a prospective cohort of 8,943 patients with angiographically confirmed TVD at Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China. The primary end point was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. In total, 2,819 patients with NSTE-ACS who received CABG (43.6%) or PCI (56.4%) were included, among whom 32.7% were of 65-74 years, 7.2% were ≥75 years, and 22.6% were women. The median follow-up duration was 6.8 years. The superiority of CABG relative to PCI in terms of MACCE was decreased with age (adjusted hazard ratio [HR] [95% confidence interval (CI)]: <65 years: 0.662 [0.495-0.885], p = 0.005; 65-74 years: 0.700 [0.512-0.956], p = 0.025; ≥75 years: 0.884 [0.529-1.479], p = 0.640) and was only seen in men (adjusted HR [95% CI]: men: 0.668 [0.526-0.848], p = 0.001; women: 0.713 [0.505-1.006], p = 0.054). Significant treatment-by-sex and treatment-by-age interactions were observed in patients ≥ 75 years and women, respectively, (p interaction with sex = 0.001; p interaction with age = 0.002). Conclusion: Coronary artery bypass grafting is favorable for most NSTE-ACS patients with TVD. The preponderance of CABG over PCI disappeared in patients ≥ 75 years and women. PCI is superior in women ≥ 75 years.

Implications of structural right ventricular involvement in patients with hypertrophic cardiomyopathy.

AIMS: In the clinical practice, the right ventricular (RV) manifestations have received less attention in hypertrophic cardiomyopathy (HCM). This paper aimed to evaluate the risk prediction value and genetic characteristics of RV involvement in HCM patients. METHODS AND RESULTS: A total of 893 patients with HCM were recruited. RV hypertrophy, RV obstruction, and RV late gadolinium enhancement were evaluated by echocardiography and/or cardiac magnetic resonance. Patients with any of the above structural abnormalities were identified as having RV involvement. All patients were followed with a median follow-up time of 3.0 years. The primary endpoint was cardiovascular death; the secondary endpoints were all-cause death and heart failure (HF)-related death. Survival analyses were conducted to evaluate the associations between RV involvement and the endpoints. Genetic testing was performed on 669 patients. RV involvement was recognized in 114 of 893 patients (12.8%). Survival analyses demonstrated that RV involvement was an independent risk factor for cardiovascular death (P = 0.002), all-cause death (P = 0.011), and HF-related death (P = 0.004). These outcome results were then confirmed by a sensitivity analysis. Genetic testing revealed a higher frequency of genotype-positive in patients with RV involvement (57.0% vs. 31.0%, P < 0.001), and the P/LP variants of MYBPC3 were more frequently identified in patients with RV involvement (30.4% vs. 12.0%, P < 0.001). Logistic analyses indicated the independent correlation between RV involvement and these genetic factors. CONCLUSION: RV involvement was an independent risk factor for cardiovascular death, all-cause death and HF-related death in HCM patients. Genetic factors might contribute to RV involvement in HCM.

Identification of heart failure with preserved ejection fraction helps risk stratification for hypertrophic cardiomyopathy.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is the dominant form of heart failure (HF). We here aimed to investigate the characteristics and prognosis of HFpEF in patients with hypertrophic cardiomyopathy (HCM). METHODS: This was a prospective cohort study and patients with HCM with available NT-proBNP results were enrolled. Patients were categorized into HFpEF [defined as LVEF ≥50%, with symptoms or signs of HF, and N-terminal pro-brain natriuretic peptide ≥800 pg/mL according to American Heart Association (AHA) criteria] and without heart failure (non-HF). The outcomes of interest were all-cause death, cardiovascular death, and sudden cardiac death (SCD). RESULTS: Of 1178 included patients with HCM, 513 (43.5%) were identified as having HFpEF according to AHA criteria. Compared with non-HF patients, patients with HFpEF had significantly larger maximal wall thickness (P < 0.001), higher maximal left ventricular outflow tract gradient (P < 0.001), higher proportion of atrial fibrillation (P < 0.001), higher incidence of all-cause death (log-rank test, P = 0.002), and cardiovascular death (log-rank test, P = 0.005). Multivariable Cox analysis showed that patients with HFpEF had a nearly two-fold higher risk of all-cause death (adjusted HR = 1.80, 95% CI 1.11-2.90; P = 0.017) and cardiovascular death (adjusted HR =1.82, 95% CI 1.05-3.18; P = 0.033) than non-HF patients. CONCLUSIONS: Patients with HCM have a high prevalence of HFpEF and those with HFpEF present greater disease severity and higher mortality than non-HF patients, and thus may require an appropriate and more aggressive treatment for HF management. Identification of patients with HFpEF using AHA criteria can provide guidance on patient risk stratification for patients with HCM.

Relationship Between High-Sensitivity C-Reactive Protein and Long-Term Outcomes in Elderly Patients With 3-Vessel Disease.

The prognostic value of high-sensitivity C-reactive protein (hsCRP) in complex coronary artery disease has not been fully established. We aimed to determine the association between hsCRP and long-term outcomes in elderly patients with 3-vessel disease (TVD). From April 2004 to February 2011, 3069 patients aged ≥65 years with TVD were consecutively enrolled and received medical treatment alone, percutaneous coronary intervention, or coronary artery bypass grafting. The patients were divided into 2 groups according to their hsCRP levels: <3.00 mg/L (62.1%) and ≥3.00 mg/L (37.9%). The mean age was 71 ± 4 years. The high hsCRP group had more risk factors and more frequently received conservative treatment than the low hsCRP group. During a median follow-up period of 6.2 years, elevated hsCRP was significantly associated with increased all-cause death (19.5% vs 29.6%, P < .001), cardiac death (9.4% vs 15.2%, P = .001), and major adverse cardiovascular and cerebrovascular events (34.1% vs 42.5%, P = .001). Multivariable Cox regression analyses revealed that hsCRP was an independent predictor for all of these events. Combining hsCRP with Synergy between PCI with TAXUS and Cardiac Surgery score II further improved the predictive power of the score. The relationship between hsCRP and mortality was relatively consistent across subgroups. Overall, hsCRP could prove useful for risk prediction in elderly patients.

Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease.

Background: There is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of direct bilirubin (DB) in patients with complex acute coronary syndrome (ACS). Methods: From April 2004 to February 2011, 5,322 ACS patients presenting with three-vessel disease were consecutively enrolled. Disease severity and complexity were determined by SYNTAX score (SS) and SS II. The primary endpoint was all-cause death, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE). Stratification of normal glucose regulation, prediabetes, and diabetes was based on a previous diagnosis, hypoglycemic medications, fasting blood glucose, and hemoglobin A1c. Results: Subjects were divided into quartiles according to baseline DB (µmol/L): Q1 (0-1.6), Q2 (1.61-2.20), Q3 (2.21-2.80), and Q4 (>2.80). Multivariable logistic regression analysis showed that DB was an independent predictor of intermediate-high SS. During a median follow-up time of 6.5 years, elevated DB was associated with more all-cause death (p < 0.001) but not MACCE. DB remained to be predictive of all-cause death in the multivariable Cox regression model (Q2 vs. Q1: HR 1.043, 95% CI 0.829-1.312, p = 0.719; Q3 vs. Q1: HR 1.248, 95% CI 1.001-1.155, p = 0.048; Q4 vs. Q1: HR 1.312, 95% CI 1.063-1.620, p = 0.011). When subjects are stratified according to glucose metabolism regulation and treatment strategies, the predictivity of DB was only profound in patients with diabetes or with conservative treatment. Additionally, incorporating DB further improved the discrimination and reclassification abilities of SS II for risk prediction. Conclusion: DB is a potential biomarker for predicting lesion severity and long-term outcomes in ACS patients.

Real-world long-term outcomes based on three therapeutic strategies in very old patients with three-vessel disease.

BACKGROUND: There are relatively limited data regarding real-world outcomes in very old patients with three-vessel disease (3VD) receiving different therapeutic strategies. This study aimed to perform analysis of long-term clinical outcomes of medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) in this population. METHODS: We included 711 patients aged ≥ 75 years from a prospective cohort of patients with 3VD. Consecutive enrollment of these patients began from April 2004 to February 2011 at Fu Wai Hospital. Patients were categorized into three groups (MT, n = 296; CABG, n = 129; PCI, n = 286) on the basis of different treatment strategies. RESULTS: During a median follow-up of 7.25 years, 262 deaths and 354 major adverse cardiac and cerebrovascular events (MACCE) occurred. Multivariate Cox analysis showed that the risk of cardiac death was significantly lower for CABG compared with PCI (adjusted hazard ratio [HR] = 0.475, 95% confidence interval [CI] 0.232-0.974, P = 0.042). Additionally, MACCE appeared to show a trend towards a better outcome for CABG (adjusted HR = 0.759, 95% CI 0.536-1.074, P = 0.119). Furthermore, CABG was significantly superior in terms of unplanned revascularization (adjusted HR = 0.279, 95% CI 0.079-0.982, P = 0.047) and myocardial infarction (adjusted HR = 0.196, 95% CI 0.043-0.892, P = 0.035). No significant difference in all-cause death between CABG and PCI was observed. MT had a higher risk of cardiac death than PCI (adjusted HR = 1.636, 95% CI 1.092-2.449, P = 0.017). Subgroup analysis showed that there was a significant interaction between treatment strategy (PCI vs. CABG) and sex for MACCE (P = 0.026), with a lower risk in men for CABG compared with that of PCI, but not in women. CONCLUSIONS: CABG can be performed with reasonable results in very old patients with 3VD. Sex should be taken into consideration in therapeutic decision-making in this population.

Real-world outcomes of different treatment strategies in patients with diabetes and three-vessel coronary disease: a mean follow-up 6.3 years study from China.

BACKGROUND: Patients with diabetes and triple-vessel disease (TVD) are associated with a high risk of events. The choice of treatment strategies remains a subject of discussion. In the real-world, we aim to compare the outcomes of medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) treatment strategies in patients with diabetes and TVD. METHODS: A total of 3117 consecutive patients with diabetes and TVD were enrolled. The primary endpoint was all-cause death and the secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE, composite of all-cause death, myocardial infarction, or stroke). RESULTS: During the mean follow-up of 6.3 ± 2.6 years, 573 (18.4%) deaths and 1094 (35.1%) MACCE occurred. Multivariate analysis showed that PCI (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.32-0.51) and CABG (HR 0.33, 95% CI 0.26-0.44) were associated with a lower risk of death compared with MT, with no difference between the PCI and CABG groups. When MACCE was the endpoint, PCI (HR 0.71, 95% CI 0.60-0.84) and CABG (HR 0.48, 95% CI 0.39-0.57) had a lower risk than MT. CABG was associated with a significantly lower risk of MACCE compared with PCI (HR 0.67, 95% CI 0.55-0.81), which was mainly attributed a lower risk in myocardial infarction, but a higher risk of stroke. CONCLUSIONS: In this big real-world data and intermediate-term follow-up study, for patients with diabetes and TVD, PCI and CABG were associated with a lower risk of death and MACCE more than MT. The results suggest the importance of appropriate revascularization for diabetic patients with TVD. However, CABG was not associated with a lower risk of death, but with a lower risk of MACCE, compared with PCI. In the future, we perhaps should strengthen comprehensive treatment in addition to PCI or CABG.

Prediabetes and long-term outcomes in patients with three-vessel coronary artery disease: A large single-center cohort study.

AIMS/INTRODUCTION: Whether detection of prediabetes by routinely testing hemoglobin A1c and fasting plasma glucose in three-vessel disease patients could identify individuals at high risk of future cardiovascular disease events remains unclear. This study evaluated the relationship between different glycemic status and clinical outcomes in this specific population. MATERIALS AND METHODS: This study included 8,891 Chinese patients with three-vessel disease. Patients were categorized according to their glycemic status (normoglycemia [NG], n = 3,195; prediabetes, n = 1,978; diabetes mellitus, n = 3,718). RESULTS: The median follow-up time was 7.5 years, during which 1,354 deaths and 2,340 major adverse cardiac and cerebrovascular events occurred. Compared with the NG group, patients in the prediabetes and diabetes mellitus groups had more comorbidities. After adjusting for confounders, the diabetes mellitus group had a higher risk of all-cause death (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.20-1.53; P < 0.001), cardiac death (HR 1.35, 95% CI 1.14-1.61; P = 0.001) and major adverse cardiac and cerebrovascular events (HR 1.22, 95% CI 1.11-1.34; P < 0.001) compared with the NG group, whereas the prediabetes and NG groups had no significant difference. The diabetes mellitus group also had a higher risk of stroke compared with the NG group (HR 1.22, 95% CI 1.02-1.46; P = 0.031). CONCLUSIONS: In the context of three-vessel disease, prediabetes patients have comparable long-term outcomes in terms of major adverse cardiac and cerebrovascular events, cardiac death and all-cause death to those with NG. Routine screening of glycemic metabolism based on hemoglobin A1c and fasting plasma glucose might be valuable to identify individuals with diabetes mellitus who are at high risk of future cardiovascular disease events and individuals with prediabetes who are at high risk of progressing to diabetes mellitus.

Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease.

BACKGROUND AND AIMS: Whether routine assessment of FT3/FT4 ratio in euthyroid patients with three-vessel disease (3VD) could help identify high-risk individuals remains unclear. This study evaluated the relationship between FT3/FT4 ratio and long-term clinical outcomes in this specific population. METHODS AND RESULTS: This study included 2106 euthyroid patients with 3VD (stenoses of ≥50% in right coronary artery, left circumflex and left anterior descending). Patients were categorized into three groups according to tertiles of FT3/FT4 ratio (Q1>2.58,n = 704; 2.2 ≤ Q2<2.58, n = 706; Q3<2.22, n = 696). The median follow-up time was 5.3 years, during which 206 deaths and 332 MACCEs (consisting of all-cause death, myocardial infarction, and stroke) occurred. Compared with the other two groups, patients with low level of FT3/FT4 ratio tended to be female, older, diabetic, and had significantly higher incidences of all-cause death, cardiac death and MACCE (all P < 0.05). Cox regression analysis showed that patients with low level of FT3/FT4 ratio had higher risks of long-term cardiac death (adjusted HR = 1.87, 95% CI 1.06-3.28, P = 0.030) and MACCE (adjusted HR = 1.43, 95% CI 1.07-1.93, P = 0.017) than those with high level of FT3/FT4 ratio. Subgroup analysis showed there was a significant interaction between FT3/FT4 ratio and age (≥65 years vs.<65 years) for MACCE (P = 0.029). CONCLUSION: Low level of FT3/FT4 ratio is independently associated with an increased risk of long-term cardiac death and MACCE in euthyroid patients with 3VD. Routine assessment of FT3/FT4 ratio might be helpful to identify high-risk individuals in this specific population.

Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease.

Three-vessel disease (TVD) is a severe coronary heart disease (CHD) with poor prognosis. Niemann-Pick C1-like 1 (NPC1L1) is a transporter protein for exogenous cholesterol absorption, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is a rate-limiting enzyme for cholesterol synthesis. We aimed to investigate the association between NPC1L1 and HMGCR gene polymorphisms and major adverse cardiac and cerebrovascular events (MACCE) in patients with TVD. A total of 342 TVD patients were consecutively enrolled and followed up for 1-year MACCE (a composite of all-cause death, myocardial infarction, revascularization, readmission, and stroke) as TVD event group, and 344 patients without CHD were control group. Four single-nucleotide polymorphisms (SNPs), rs11763759, rs4720470, rs2072183, and rs2073547, on NPC1L1 gene and four SNPs, rs12916, rs2303151, rs2303152, and rs4629571, on HMGCR gene were genotyped. Multivariate logistic regression analysis showed that rs4720470 of NPC1L1 was associated with higher risk of TVD with MACCE in codominant model (odds ratio [OR]: 1.315; 95% confidence intervals [CI]: 1.007-1.716, p = 0.044), and that rs2303151 of HMGCR was associated with higher in recessive (OR: 3.383; 95% CI: 1.040-10.998, p = 0.043) and codominant (OR: 1.458; 95% CI: 1.038-2.047, p = 0.030) model, respectively. Patients with both variant rs4720470 in codominant model and variant rs2303151 in recessive model related to a higher risk (OR: 6.772, CI: 1.338-34.280; p = 0.021). We reported for the first time that the rs4720470 on NPC1L1 gene and rs2303151 on HMGCR gene were associated with risk of 1-year MACCE in TVD.