The Association Between the Use of Cholinesterase Inhibitors and Cardiovascular Events Among Older Patients With Alzheimer Disease

ObjectiveTo evaluate the association between the use of cholinesterase inhibitors (ChEIs) and incident cardiovascular events (CVEs) among older patients with Alzheimer disease (AD).Patients and MethodsThis retrospective cohort study was conducted with a new-user design and active-comparator design. The data source was the 2005–2014 Full Population file from the Health and Welfare Database in Taiwan. Patients were included if they were aged 50 years or older and had been diagnosed with AD between January 1, 2006, and December 31, 2010. The association between ChEI use and the risk of CVEs was investigated in patients with AD. Among the ChEI users, the risk of CVEs was further compared between patients with different cumulative doses and different ChEI treatment strategies. The propensity score method, which included matching and inverse probability of treatment weighting, was used to balance the potential confounders. A Cox proportional hazards model with competing risks was used to estimate the hazard ratio of CVEs.ResultsThe study included 6070 patients with AD. After covariate adjustment, ChEI users had a significantly lower risk of CVEs than nonusers (hazard ratio, 0.57; 95% CI, 0.51 to 0.62). Among ChEI users, patients with a high cumulative dose had a significantly lower risk of CVEs than those with a low cumulative dose (hazard ratio, 0.82; 95% CI, 0.70 to 0.96).ConclusionThe use of ChEIs was associated with a decreased risk of incident CVEs among patients with AD. The cardioprotective effect of ChEIs showed a dose-response relationship.     

A Randomized Controlled Trial to Reduce Prehospital Delay Time in Patients With Acute Coronary Syndrome (ACS)

Background

The literature suggests that people delay too long prior to attending emergency departments with acute coronary syndrome (ACS) symptoms. This delay is referred to as prehospital delay. Patient decision delay contributes most significantly to prehospital delay.

Objectives

Using a randomized controlled trial, we tested an educational intervention to reduce patient prehospital delay in ACS and promote appropriate responses to symptoms.

Methods

Eligible patients who were admitted across five emergency departments (EDs) in Dublin were recruited to the study (n = 1944; control: 972, intervention: 972).

Results

Median baseline prehospital delay times did not differ significantly between the groups at baseline (Mann-Whitney U, p = 0.34) (Control: 4.28 h, 25^th percentile = 1.71, 75^th percentile = 17.37; Intervention 3.96 h, 25^th percentile = 1.53, 75^th percentile = 18.51). Both groups received usual in-hospital care. In addition, patients randomized to the intervention group received a 40-min individualized education session using motivational techniques. This was reinforced 1 month later by telephone. Of the 1944, 314 (16.2%) were readmitted with ACS symptoms: 177 (18.2%) and 137 (14.1%) of the intervention and control groups, respectively. Prehospital delay times were again measured. Median delay time was significantly lower in the intervention compared to the control group (1.7 h vs. 7.1 h; p ≤ 0.001). Appropriately, those in the intervention group reported their symptoms more promptly to another person (p = 0.01) and fewer consulted a general practitioner (p = 0.02). There was no significant difference in ambulance use (p = 0.51) or nitrate use (p = 0.06) between the groups.

Conclusion

It is possible to reduce prehospital delay time in ACS, but the need for renewed emphasis on ambulance use is important.     

Association Between the Volume of Inpatient Rehabilitation Therapy and the Risk of All-Cause and Cardiovascular Mortality in Patients With Ischemic Stroke

Objective

To investigate the relationship between the volume of inpatient rehabilitation therapy and mortality among patients with acute ischemic stroke, as well as to assess whether the association varies with respect to stroke severity.

Design

A retrospective study with a cohort of consecutive patients who had acute ischemic stroke between January 1, 2008, and June 30, 2009.

Setting

Referral medical center.

Participants

Adults with acute ischemic stroke (N=1277) who were admitted to a tertiary hospital.

Interventions

Not applicable.

Main Outcome Measure

Stroke-related mortality.

Results

During the median follow-up period of 12.3 months (ranging from January 1, 2008, to December 31, 2009), 163 deaths occurred. Greater volume of rehabilitation therapy was associated with a reduced risk of all-cause and cardiovascular mortality (P for trend <.001 for both). Compared with the first tertile, the third tertile of rehabilitation volume was associated with a 55% lower risk of all-cause mortality (hazard ratio [HR]=.45; 95% confidence interval [CI], .30–.65) and a 50% lower risk of cardiovascular mortality (HR=.50; 95% CI, .31–.82). The association did not vary with respect to stroke severity (P for interaction = .45 and .73 for all-cause and cardiovascular mortality, respectively).

Conclusions

The volume of inpatient rehabilitation therapy and mortality were significantly inversely related in the patients with ischemic stroke. Thus, further programs aimed at promoting greater use of rehabilitation services are warranted.     

Association of Metabolic Phenotypes With Coronary Artery Disease and Cardiovascular Events in Patients With Stable Chest Pain

OBJECTIVEObesity and metabolic syndrome are associated with major adverse cardiovascular events (MACE). However, whether distinct metabolic phenotypes differ in risk for coronary artery disease (CAD) and MACE is unknown. We sought to determine the association of distinct metabolic phenotypes with CAD and MACE.RESEARCH DESIGN AND METHODSWe included patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) who underwent coronary computed tomography (CT) angiography. Obesity was defined as a BMI ≥30 kg/m² and metabolically healthy as less than or equal to one metabolic syndrome component except diabetes, distinguishing four metabolic phenotypes: metabolically healthy/unhealthy and nonobese/obese (MHN, MHO, MUN, and MUO). Differences in severe calcification (coronary artery calcification [CAC] ≥400), severe CAD (≥70% stenosis), high-risk plaque (HRP), and MACE were assessed using adjusted logistic and Cox regression models.RESULTSOf 4,381 patients (48.4% male, 60.5 ± 8.1 years of age), 49.4% were metabolically healthy (30.7% MHN and 18.7% MHO) and 50.6% unhealthy (22.3% MUN and 28.4% MUO). MHO had similar coronary CT findings as compared with MHN (severe CAC/CAD and HRP; P > 0.36 for all). Among metabolically unhealthy patients, those with obesity had similar CT findings as compared with nonobese (P > 0.10 for all). However, both MUN and MUO had unfavorable CAD characteristics as compared with MHN (P ≤ 0.017 for all). A total of 130 events occurred during follow-up (median 26 months). Compared with MHN, MUN (hazard ratio [HR] 1.61 [95% CI 1.02–2.53]) but not MHO (HR 1.06 [0.62–1.82]) or MUO (HR 1.06 [0.66–1.72]) had higher risk for MACE.CONCLUSIONSIn patients with stable chest pain, four metabolic phenotypes exhibit distinctly different CAD characteristics and risk for MACE. Individuals who are metabolically unhealthy despite not being obese were at highest risk in our cohort.     

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

OBJECTIVETo investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.RESEARCH DESIGN AND METHODSIn this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.RESULTSCardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8–8.7) (120.6 mg/dL [104.4–156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication.CONCLUSIONSIncreased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.     

Association of Elevated Triglycerides With Increased Cardiovascular Risk and Direct Costs in Statin-Treated Patients

ObjectiveTo retrospectively investigate the real-world impact of elevated triglyceride (TG) levels on cardiovascular (CV) outcomes, medical resource utilization, and medical costs using observational administrative claims data from the Optum Research Database.MethodsPatients with one or more claims for statin therapy between January 1, 2010, and December 31, 2010, and 6 months or more of baseline data prior to the index date were eligible for inclusion in the study. Patients aged 45 years or older with diabetes and/or atherosclerotic CV disease were included and analyzed in an elevated TG cohort (≥150 mg/dL) vs a comparator cohort with TG levels less than 150 mg/dL and high-density lipoprotein cholesterol (HDL-C) levels greater than 40 mg/dL.ResultsIn the elevated TG vs propensity-matched comparator cohorts (both N=23,181 patients), the mean age was 62.2 vs 62.6 years, mean follow-up was 41.4 vs 42.5 months, 49.7% (11,518) vs 49.5% (11,467) were female, 83.7% (19,392) vs 84.0% (19,478) had diabetes, and 29.8% (6915) vs 29.3% (6800) had atherosclerotic CV disease. In the elevated TG (N=27,471 patients) vs comparator (N=32,506 patients) cohorts, multivariate analysis revealed significantly greater risk of composite major CV events (hazard ratio [HR], 1.26; 95% CI, 1.19-1.34; P<.001), nonfatal myocardial infarction (HR, 1.32; 95% CI, 1.20-1.45; P<.001), nonfatal stroke (HR, 1.14; 95% CI, 1.04-1.24; P=.004), and need for coronary revascularization (HR, 1.46; 95% CI, 1.33-1.61; P<.001) but not unstable angina (P=.53) or CV death (P=.23). Increased CV risk was maintained with the addition of non–HDL-C to the multivariate model and with high and low HDL-C subgroup analysis. Total direct health care costs (cost ratio, 1.12; 95% CI, 1.08-1.16; P<.001) and inpatient hospital stays (HR, 1.13; 95% CI, 1.10-1.17; P<.001) were significantly higher in the elevated TG cohort vs the comparator cohort.ConclusionStatin-treated patients with TG levels of 150 mg/dL or greater had worse CV and health economic outcomes than those with well-managed TG (<150 mg/dL) and HDL-C (>40 mg/dL) levels.     

Early Detection of Pancreatic Cancer in Patients With Chronic Liver Disease Under Hepatocellular Carcinoma Surveillance

ObjectiveTo evaluate whether patients with hepatitis B virus (HBV)– and hepatitis C virus (HCV)–related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC).Patients and MethodsWe retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ² test.ResultsThe UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease.ConclusionPatients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.     

Apatinib Combined With Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus: A Multicenter Retrospective Study

PurposeStudies focusing on the effects of combined transcatheter arterial chemoembolization (TACE) + the tyrosine kinase inhibitor apatinib in the treatment of patients with hepatocellular carcinoma (HCC), with the location and extent of portal vein tumor thrombus (PVTT) assessed as the main variable, are rare. This multicenter, retrospective, controlled study was performed to compare the efficacy and tolerability of TACE + apatinib and TACE alone in patients with HCC and PVTT.MethodsWe retrospectively analyzed data from patients with nonresectable HCC and PVTT who underwent treatment with TACE + apatinib or TACE alone between January 2015 and January 2016. Outcomes in patients who underwent TACE + apatinib were compared with the outcomes of patients who underwent TACE alone, by using the Kaplan–Meier method, according to PVTT type: PVTT in the main portal vein (type A), PVTT in the first-order portal vein branch (type B), and PVTT in second- or lower-order portal vein branches (type C).FindingsOne hundred eighty-eight patients were included in the analysis; 85 underwent treatment with TACE + apatinib and 103 underwent treatment with TACE. TACE + apatinib was associated with a significantly greater median survival compared with TACE alone in patients with PVTT type B (12.2 vs 7.5 months; P < 0.001) or type C (13.7 vs 7.2 months; P = 0.006). Along with treatment strategies and α-fetoprotein, the absence of main PVTT was an independent factor predictive of survival on uni- and multivariate analysis. Apatinib-related grade 3 adverse events occurred in 27 patients (31.8%).ImplicationsTACE + apatinib can be of potential benefit to patients with advanced HCC with tumor thrombus in the first- and lower-order portal vein branches. Adverse events with apatinib need to be monitored during application, despite the manageable appearance.     

时间-强度量化分析与原发性肝癌预后的初步研究

目的 探讨超声造影时间-强度量化分析与临床病理因素的关系,分析其在HCC患者预后中的作用.方法 73例HCC超声造影结果进行时间-强度量化分析;探讨超声造影时间-强度量化分析和血管内皮生长因子(VEGF)表达、微血管密度(MVD)以及临床病理因素之间的关系;探讨超声造影时间-强度量化分析判断HCC预后的作用.结果 37例HCC组织中VEGF呈阳性表达(50.7％).MVD与VEGF表达具有显著相关性(P＜0.05).VEGF阳性表达组中增强时间、消退时间及曲线下面积与阴性表达组间有显著性意义(P＜0.05).超声造影时间-强度分析参数与肿瘤大小无关(P＞0.05),而汇管区癌栓组超声造影增强时间与汇管区无癌栓组间有显著性意义(P＜0.05).肿瘤大小、VEGF阳性表达、汇管区癌栓与3年复发率和生存率有关.结论 超声造影可帮助临床明确病变性质,时间-强度量化分析结合临床病理因素可作为判断预后的重要参考.     

Association Between Alcohol Consumption and Risk of Cardiovascular Disease and All-Cause Mortality in Patients With Hypertension: A Meta-Analysis of Prospective Cohort Studies

ObjectiveTo conduct a meta-analysis summarizing the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in relation to alcohol consumption in patients with hypertension, focusing on clarifying dose-response associations.Patients and MethodsPubMed and EMBASE were searched for eligible prospective cohort studies from December 3, 1949, through January 18, 2014. The semi-parameter method and dose-response analysis were used.ResultsNine studies (11 cohorts) were included in the meta-analysis. Compared with the lowest alcohol level (abstainers/occasional drinkers), the pooled relative risk (RR) was 0.72 (95% CI, 0.68-0.77) for the third highest category (median, 10 g/d), 0.81 (95% CI, 0.71-0.93) for the second highest category (median, 20 g/d), and 0.60 (95% CI, 0.54-0.67) for the highest category (median, 30 g/d). A J-shaped relationship between alcohol use and ACM was observed, and the nadir (RR, 0.82; 95% CI, 0.76-0.88) was found to be at a dose of 8 to 10 g of alcohol consumption per day.ConclusionFindings of this meta-analysis suggest that low-to-moderate alcohol consumption was inversely significantly associated with the risk of CVD and ACM in patients with hypertension.     

The Association Between Autonomic Dysfunction and Survival in Male Patients with Advanced Cancer: A Preliminary Report

ContextAutonomic nervous system dysfunction (AD) is a common syndrome in patients with advanced cancer. It is associated with decreased survival in several patient populations, including diabetes mellitus, heart failure, and neurological diseases. Based on this evidence, we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer.ObjectivesThe objective of this preliminary study was to test the association between AD, as measured by the standardized Ewing test and heart rate variability (HRV) measures, and survival in this patient population.MethodsWe examined the relationship between survival and parameters of AD in subjects who participated in a prospective study of autonomic dysfunction and hypogonadism in male patients with advanced cancer. Eligibility criteria were defined based on the prospective study protocol. We collected demographic information, date of death (obtained from the online Social Security Death Index database), date of study entry, and Ewing and HRV scores. We defined survival as the interval between study entry and date of death. A survival analysis was used to test the association between survival (in days) and Ewing test (0–5) and measures of HRV, including time domain (standard deviation of normal to normal beat interval [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients were still alive at the time of this study and included in the survival analysis as being censored.ResultsForty-seven male patients were included in this study. Median age was 59 years (range: 20–79), and 30 out of 47 (63%) were Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of 47 (80%) of the patients. Median Ewing score was 3 (1–5), indicating moderate to severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002). There was a significant association between abnormal Ewing score and survival (P < 0.0001) and abnormal SDNN HRV and survival (P = 0.056).ConclusionAD is associated with shorter survival in male patients with advanced cancer. Further longitudinal research in a large cohort is justified based on.     

Exposure-Response (Safety) Analysis to Identify Linifanib Dose for a Phase III Study in Patients With Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths and the fifth most common cancer globally. Hepatocellular carcinoma produces highly vascular tumors that overexpress vascular endothelial growth factor (VEGF), thus making VEGF a promising therapeutic target. The competitive inhibitor linifanib (ABT-869) has selectivity for VEGF and platelet-derived growth factor (PDGF) receptors and minimal activity against unrelated tyrosine and serine and threonine kinases. However, the optimal dosing regimen for linifanib in HCC patients is not yet known.

Objective

This study attempts to identify a linifanib dose or dosing regimen with an acceptable safety profile for a Phase III study in HCC patients.

Methods

The pharmacokinetic (PK) properties of linifanib were characterized from 2 Phase I and 3 Phase II clinical trials. Of the 266 patients evaluated, the median weight was 68 kg (range, 35-177 kg), 64% were male, and 87.6% of patients received an oral solution of linifanib, whereas 12.4% received a tablet formulation. Approximately 95% of patients received drug based on weight, with the remaining on a fixed-dosing regimen. A population PK analysis was conducted to characterize the linifanib exposure for each patient. Linifanib C_max and AUC derived from the population PK properties were correlated with the rates of adverse events (AEs).

Results

Linifanib PK properties are dose proportional for the 0.10-mg/kg to 0.25-mg/kg once daily dose range and are time independent after repeated oral dosing. The T_max of linifanib is approximately 3 hours, and the t_½ is approximately 1 day. The most common AEs related to linifanib PK were hypertension (P = 0.02 for C_max and P = 0.01 for AUC), diarrhea (P = 0.001 for C_max and P = 0.0012 for AUC), proteinuria (P = 0.001 for C_max and P = 0.002 for AUC), and asthenia (P = 0.03 for AUC). Weight and sex were identified as covariates for C_max, and sex was identified as a covariate for AUC. The predicted AE range for females was slightly higher compared with males; however, the AE range is tighter for the weight range for fixed dosing compared with weight-based dosing, regardless of sex.

Conclusions

The PK properties of linifanib support a one-compartment model with first-order absorption and elimination. Comparison of weight-based and fixed dosing revealed predicted AE rates to be similar, with a tighter AE range for fixed dosing. The safety profile of linifanib, therefore, supports a 17.5 mg fixed starting dose for Phase III clinical studies.     

The Association Between Emergency Department Crowding and Adverse Cardiovascular Outcomes in Patients with Chest Pain

Objectives: While emergency department (ED) crowding is a worldwide problem, few studies have demonstrated associations between crowding and outcomes. The authors examined whether ED crowding was associated with adverse cardiovascular outcomes in patients with chest pain syndromes (chest pain or related complaints of possible cardiac origin). Methods: A retrospective analysis was performed for patients ≥30 years of age with chest pain syndrome admitted to a tertiary care academic hospital from 1999 through 2006. The authors compared rates of inpatient adverse outcomes from ED triage to hospital discharge, defined as delayed acute myocardial infarction (AMI), heart failure, hypotension, dysrhythmias, and cardiac arrest, which occurred after ED arrival using five separate crowding measures. Results: Among 4,574 patients, 251 (4%) patients developed adverse outcomes after ED arrival; 803 (18%) had documented acute coronary syndrome (ACS), and of those, 273 (34%) had AMI. Compared to less crowded times, ACS patients experienced more adverse outcomes at the highest waiting room census (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.3 to 11.0) and patient-hours (OR = 5.2, 95% CI = 2.0 to 13.6) and trended toward more adverse outcomes during time of high ED occupancy (OR = 3.1, 95% CI = 1.0 to 9.3). Adverse outcomes were not significantly more frequent during times with the highest number of admitted patients (OR = 1.6, 95% CI = 0.6 to 4.1) or the highest trailing mean length of stay (LOS) for admitted patients transferred to inpatient beds within 6 hours (OR = 1.5, 95% CI = 0.5 to 4.0). Patients with non-ACS chest pain experienced more adverse outcomes during the highest waiting room census (OR = 3.5, 95% CI = 1.4 to 8.4) and patient-hours (OR = 4.3, 95% CI = 2.6 to 7.3), but not occupancy (OR = 1.8, 95% CI = 0.9 to 3.3), number of admitted patients (OR = 0.6, 95% CI 0.4 to 1.1), or trailing LOS for admitted patients (OR = 1.2, 95% CI = 0.6 to 2.0). Conclusions: There was an association between some measures of ED crowding and a higher risk of adverse cardiovascular outcomes in patients with both ACS-related and non–ACS-related chest pain syndrome.     

冠状动脉硬化性心脏病患者死亡时间及其时间护理研究

目的分析冠状动脉硬化性心脏病（简称冠心病）患者死亡时间的分布趋势,讨论《内经》中关于冠心病患者死亡时间医学理论的科学性及其对时间护理的指导作用。方法采用多阶段整群抽样法,从湖南省123个县（区）级行政区所辖医院抽取345例冠心病死亡病例,调查患者死亡的具体时间,用圆分布统计方法分析数据的时间集中趋势。结果345例冠心病患者的死亡时间有集中在1月8日的趋势（P〈0．05）;具体死亡时点无集中趋势（P〉0．05）。春季死亡时间集中趋势不明显（P〈0．05）;夏季死亡时间有集中在12：52分的趋势（P〈0．05）;秋季死亡时间无集中趋势（P〉0．05）;冬季死亡时间有集中在0：32分的趋势（P〈0．05）。结论调查分析结果与《内经》心病死亡时间观点一致,可为预测冠心病死亡时间提供参考,可利用《内经》心病时间医学理论指导冠心病患者的时间护理。