Circadian Dependence of Infarct Size and Acute Heart Failure in ST Elevation Myocardial Infarction.

OBJECTIVES: There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI. METHODS: We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight-6:00 A.M., 6:00 A.M.-noon, noon-6:00 P.M. and 6:00 P.M.-midnight. We used peak creatine kinase as a surrogate marker of infarct size. RESULTS: Midnight-6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight-6:00 A.M. patients and lowest among 6:00 A.M.-noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight-6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.-noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001). CONCLUSION: We observed a circadian peak and nadir in infarct size during STEMI onset from midnight-6:00A.M and 6:00A.M.-noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.

Use of Population-Based Cancer Registry Data to Determine the Effect of Timely Treatment on the Survival of Colorectal Cancer Patients.

INTRODUCTION: Colorectal cancer is the third most common cancer in the world. In Singapore, it was the most common cancer in males and second most common cancer in females from 2009 to 2013. The incidence for colorectal cancer is declining, but the mortality remains high. Cancer of the colon is a highly treatable and curable disease when it is localized to the bowel. Timely treatment of cancer, which is defined as the interval between date of diagnosis and starting date of treatment within an assigned time frame, plays an important role for the survival of patients. This is the first study in Southeast Asia looking at multiethnic groups. The study attempts to determine the effect of timely treatment on survival of colorectal cancer patients by using the Singapore cancer registry data. METHODS: Histologically proven colorectal cancer cases of the residents in Singapore diagnosed in 2008-2012 were included. Exclusion criteria for the study were neuroendocrine carcinomas, soft tissue sarcoma, and lymphoma of the bowel. Bivariate analysis was used to describe patient demographic and disease characteristics by survival status of patient as well as by treatment types and stage group. Timely surgery, adjuvant therapy, and neoadjuvant treatment modalities were defined. Cox regression analysis was used to determine the effect of timely treatment on survival of patients by controlling other independent variables of age, sex, the stage of disease, and ethnicity. RESULTS: A total of 7,739 patients were included in this study. Colorectal cancer was more common in males (55.8%) than in females (44.2%), with a median age of 65.5 years for males and 67.1 years for females. It was more common in Chinese ethnicity (87.7%) followed by Malay (7.4%) and Indian (3.2%). About 40% of patients were diagnosed in early stage and 54.3% in late stage. Primary subsites in order of frequency were sigmoid colon (29%) and rectum (24.4%), followed by rectosigmoid colon (11.4%). About 86% of patients had surgery, of which 47% were treated by surgery alone. More than 75% of patients received timely treatment. Cox regression analysis produced a hazard ratio (HR) of 1.18 (95% CI, 1.02-1.36) for patients who did not receive any type of timely first treatment, an HR of 1.35 (95% CI, 1.17-1.57) for patients with no timely surgery, an HR of 1.4 (95% CI, 1.21-1.62) for patients with no timely adjuvant chemotherapy, and an HR of 2.05 (95% CI, 1.23-3.41) for patients with no timely neoadjuvant therapy. CONCLUSION: The study shows that there were significant effects of timely treatment on survival. Information on the timely treatment modalities and its benefits should be included in the public education and emphasized during the treatment planning with patients for better compliance and improved outcomes. Some delays are avoidable and perhaps the causes of these avoidable delays should be identified and resolved to further enhance quality of service in health care.

Differences in late cardiovascular mortality following acute myocardial infarction in three major Asian ethnic groups.

AIM: the purpose of this study was to investigate differences in long-term mortality following acute myocardial infarction (AMI) in patients from three major ethnicities of Asia. METHODS AND RESULTS: We studied 15,151 patients hospitalized for AMI with a median follow-up of 7.3 years (maximum 12 years) in six publicly-funded hospitals in Singapore from 2000-2005. Overall and cause-specific cardiovascular (CV) mortality until 2012 were compared among three major ethnic groups that represent large parts of Asia: Chinese, Malay and Indian. Relative survival of all three ethnic groups was compared with a contemporaneous background reference population using the relative survival ratio (RSR) method. The median global registry of acute coronary events score was highest among Chinese, followed by Malay and Indians: 144 (25th percentile 119, 75th percentile 173), 138 (115, 167), and 131 (109, 160), respectively, p<0.0001; similarly, in-hospital mortality was highest among Chinese (9.8%) followed by Malay (7.6%) and Indian (6.4%) patients. In contrast, 12-year overall and cause-specific CV mortality was highest among Malay (46.2 and 32.0%) followed by Chinese (43.0 and 27.0%) and Indian (35.9 and 25.2%) patients, p<0.0001. The five-year RSR was lowest among Malay (RSR 0.69) followed by Chinese (RSR 0.73) and Indian (RSR 0.79) patients, compared with a background reference population (RSR 1.00). CONCLUSIONS: We observed strong inter-Asian ethnic disparities in long-term mortality after AMI. Malay patients had the most discordant relationship between baseline risk and long-term mortality. Intensified interventions targeting Malay patients as a high-risk group are necessary to reduce disparities in long-term outcomes.