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1.  Ethnic differences in the occurrence of acute coronary syndrome: results of the Malaysian National Cardiovascular Disease (NCVD) Database Registry (March 2006 - February 2010) 
The National Cardiovascular Disease (NCVD) Database Registry represents one of the first prospective, multi-center registries to treat and prevent coronary artery disease (CAD) in Malaysia. Since ethnicity is an important consideration in the occurrence of acute coronary syndrome (ACS) globally, therefore, we aimed to identify the role of ethnicity in the occurrence of ACS among high-risk groups in the Malaysian population.
The NCVD involves more than 15 Ministry of Health (MOH) hospitals nationwide, universities and the National Heart Institute and enrolls patients presenting with ACS [ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA)]. We analyzed ethnic differences across socio-demographic characteristics, hospital medications and invasive therapeutic procedures, treatment of STEMI and in-hospital clinical outcomes.
We enrolled 13,591 patients. The distribution of the NCVD population was as follows: 49.0% Malays, 22.5% Chinese, 23.1% Indians and 5.3% Others (representing other indigenous groups and non-Malaysian nationals). The mean age (SD) of ACS patients at presentation was 59.1 (12.0) years. More than 70% were males. A higher proportion of patients within each ethnic group had more than two coronary risk factors. Malays had higher body mass index (BMI). Chinese had highest rate of hypertension and hyperlipidemia. Indians had higher rate of diabetes mellitus (DM) and family history of premature CAD. Overall, more patients had STEMI than NSTEMI or UA among all ethnic groups. The use of aspirin was more than 94% among all ethnic groups. Utilization rates for elective and emergency percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) were low among all ethnic groups. In STEMI, fibrinolysis (streptokinase) appeared to be the dominant treatment options (>70%) for all ethnic groups. In-hospital mortality rates for STEMI across ethnicity ranges from 8.1% to 10.1% (p = 0.35). Among NSTEMI/UA patients, the rate of in-hospital mortality ranges from 3.7% to 6.5% and Malays recorded the highest in-hospital mortality rate compared to other ethnic groups (p = 0.000). In binary multiple logistic regression analysis, differences across ethnicity in the age and sex-adjusted ORs for in-hospital mortality among STEMI patients was not significant; for NSTEMI/UA patients, Chinese [OR 0.71 (95% CI 0.55, 0.91)] and Indians [OR 0.57 (95% CI 0.43, 0.76)] showed significantly lower risk of in-hospital mortality compared to Malays (reference group).
Risk factor profiles and ACS stratum were significantly different across ethnicity. Despite disparities in risk factors, clinical presentation, medical treatment and invasive management, ethnic differences in the risk of in-hospital mortality was not significant among STEMI patients. However, Chinese and Indians showed significantly lower risk of in-hospital mortality compared to Malays among NSTEMI and UA patients.
PMCID: PMC4229312  PMID: 24195639
2.  Are There Gender Differences in Coronary Artery Disease? The Malaysian National Cardiovascular Disease Database – Percutaneous Coronary Intervention (NCVD-PCI) Registry 
PLoS ONE  2013;8(8):e72382.
To assess whether gender differences exist in the clinical presentation, angiographic severity, management and outcomes in patients with coronary artery disease (CAD).
The study comprised of 1,961 women and 8,593 men who underwent percutaneous coronary intervention (PCI) and were included in the Malaysian NCVD-PCI Registry from 2007–2009. Significant stenosis was defined as ≥70% stenosis in at least one of the epicardial vessels.
Women were significantly older and had significantly higher rates of diabetes mellitus, hypertension, chronic renal failure, new onset angina and prior history of heart failure whereas smokers and past history of myocardial infarction were higher in men. In the ST-elevation myocardial infarction (STEMI) cohort, more women were in Killip class III-IV, had longer door-to-balloon time (169.5 min. vs 127.3 min, p<0.052) and significantly longer transfer time (300.4 min vs 166.3 min, p<0.039). Overall, women had significantly more left main stem (LMS) disease (1.3% vs 0.6%, p<0.003) and smaller diameter vessels (<3.0 mm: 45.5% vs 34.8%, p<0.001). In-hospital mortality rates for all PCI, STEMI, Non-STEMI (NSTEMI) and unstable angina for women and men were 1.99% vs 0.98%, Odds ratio (OR): 2.06 (95% confidence interval (CI): 1.40 to 3.01), 6.19% vs 2.88%, OR: 2.23 (95% CI: 1.31 to 3.79), 2.90% vs 0.79%, OR: 3.75 (95% CI: 1.58 to 8.90) and 1.79% vs 0.29%, OR: 6.18 (95% CI: 0.56 to 68.83), respectively. Six-month adjusted OR for mortality for all PCI, STEMI and NSTEMI in women were 2.18 (95% CI: 0.97 to 4.90), 2.68 (95% CI: 0.37 to 19.61) and 2.66 (95% CI: 0.73 to 9.69), respectively.
Women who underwent PCI were older with more co-morbidities. In-hospital and six-month mortality for all PCI, STEMI and NSTEMI were higher due largely to significantly more LMS disease, smaller diameter vessels, longer door-to-balloon and transfer time in women.
PMCID: PMC3754979  PMID: 24015238
3.  The joint contribution of sex, age and type of myocardial infarction on hospital mortality following acute myocardial infarction 
Heart (British Cardiac Society)  2009;95(11):895-899.
Younger, but not older, women have a higher mortality than men of similar age after a myocardial infarction (MI). We sought to determine whether this relationship is true for both ST elevation MI (STEMI) and non-ST elevation MI (NSTEMI).
Retrospective cohort study.
1057 USA hospitals participant in the National Registry of Myocardial Infarction between 2000 and 2006.
126 172 STEMI and 235 257 NSTEMI patients.
Main outcome measure
Hospital death.
For both STEMI and NSTEMI, the younger the patient's age, the greater the excess mortality risk for women compared with men, while older women fared similarly (STEMI) or better (NSTEMI) than men (p<0.0001 for the age–sex interaction). In STEMI, the unadjusted women-to-men RR was 1.68 (95% CI 1.41 to 2.01), 1.78 (1.59 to 1.99), 1.45 (1.34 to 1.57), 1.08 (1.02 to 1.14) and 1.03 (0.98 to 1.07) for age <50 years, age 50–59, age 60–69, age 70–79 and age 80–89, respectively. For NSTEMI, corresponding unadjusted RRs were 1.56 (1.31 to 1.85), 1.42 (1.27 to 1.58), 1.17 (1.09 to 1.25), 0.92 (0.88 to 0.96) and 0.86 (0.83 to 0.89). After adjusting for risk status, the excess risk for younger women compared with men decreased to approximately 15–20%, while a better survival of older NSTEMI women compared with men persisted.
Sex-related differences in short-term mortality are age-dependent in both STEMI and NSTEMI patients.
PMCID: PMC3065924  PMID: 19147625
4.  Thirty day prognosis of patients with acute pulmonary oedema complicating acute coronary syndromes 
Heart  2005;91(7):889-893.
Objectives: To investigate the characteristics of the acute coronary syndromes underlying acute pulmonary oedema and their 30 day prognosis.
Patients: 185 consecutive patients with acute coronary syndromes and acute pulmonary oedema admitted to a tertiary care centre.
Main outcome and measures: Clinical, ECG, echocardiographic, enzymatic, and angiographic features were prospectively investigated.
Results: Non-ST segment elevation myocardial infarction (NSTEMI) was the most frequent cause of acute pulmonary oedema (61%) followed by unstable angina (UA; 21%) and ST segment elevation myocardial infarction (STEMI; 18%). In each group, mean age was ⩾ 70 years, but NSTEMI patients were the oldest and ⩾ 65% of patients had chronic hypertension. Moreover, patients with NSTEMI and UA were older and had a higher incidence of diabetes, previous myocardial infarction, and moderate to severe mitral regurgitation but a similarly reduced ejection fraction (NSTEMI, 41%; UA, 39%; and STEMI, 39%) and increased incidence of diastolic dysfunction and rate of multivessel disease (94%, 87%, and 86%, respectively). However, patients with STEMI had a higher creatine kinase MB peak concentration (158 v 76 μg/l in the NSTEMI group, p < 0.001) and 30 day mortality (26% v 9% in the NSTEMI group and 8% in the UA group, p < 0.024). Multivariate analysis identified ejection fraction < 40% and a peak creatine kinase MB concentration > 100 μg/l as the main prognostic markers (p < 0.03).
Conclusions: Acute pulmonary oedema is mostly a complication of elderly hypertensive patients with NSTEMI or UA (82%) and with multivessel disease often associated with mitral regurgitation. On the other hand, the larger infarct size and higher mortality in patients with STEMI with a similarly reduced ejection fraction suggest a more extensive acute systolic loss.
PMCID: PMC1768982  PMID: 15958356
NSTEMI; prognosis; STEMI; unstable angina; acute pulmonary oedema
5.  Outcomes in Patients with Acute and Stable Coronary Syndromes; Insights from the Prospective NOBORI-2 Study 
PLoS ONE  2014;9(2):e88577.
Contemporary data remains limited regarding mortality and major adverse cardiac events (MACE) outcomes in patients undergoing PCI for different manifestations of coronary artery disease.
We evaluated mortality and MACE outcomes in patients treated with PCI for STEMI (ST-elevation myocardial infarction), NSTEMI (non ST-elevation myocardial infarction) and stable angina through analysis of data derived from the Nobori-2 study.
Clinical endpoints were cardiac mortality and MACE (a composite of cardiac death, myocardial infarction and target vessel revascularization).
1909 patients who underwent PCI were studied; 1332 with stable angina, 248 with STEMI and 329 with NSTEMI. Age-adjusted Charlson co-morbidity index was greatest in the NSTEMI cohort (3.78±1.91) and lowest in the stable angina cohort (3.00±1.69); P<0.0001. Following Cox multivariate analysis cardiac mortality was independently worse in the NSTEMI vs the stable angina cohort (HR 2.31 (1.10–4.87), p = 0.028) but not significantly different for STEMI vs stable angina cohort (HR 0.72 (0.16–3.19), p = 0.67). Similar observations were recorded for MACE (<180 days) (NSTEMI vs stable angina: HR 2.34 (1.21–4.55), p = 0.012; STEMI vs stable angina: HR 2.19 (0.97–4.98), p = 0.061.
The longer-term Cardiac mortality and MACE were significantly worse for patients following PCI for NSTEMI even after adjustment of clinical demographics and Charlson co-morbidity index whilst the longer-term prognosis of patients following PCI STEMI was favorable, with similar outcomes as those patients with stable angina following PCI.
PMCID: PMC3925145  PMID: 24551120
6.  Sex-Specific Differences in Hemodialysis Prevalence and Practices and the Male-to-Female Mortality Rate: The Dialysis Outcomes and Practice Patterns Study (DOPPS) 
PLoS Medicine  2014;11(10):e1001750.
In this study, Port and colleagues describe hemodialysis prevalence and patient characteristics by sex, compare men-to-women mortality rate with data from the general population, and evaluate sex interactions with mortality. The results show that women's survival advantage was markedly diminished in hemodialysis patients.
Please see later in the article for the Editors' Summary
A comprehensive analysis of sex-specific differences in the characteristics, treatment, and outcomes of individuals with end-stage renal disease undergoing dialysis might reveal treatment inequalities and targets to improve sex-specific patient care. Here we describe hemodialysis prevalence and patient characteristics by sex, compare the adult male-to-female mortality rate with data from the general population, and evaluate sex interactions with mortality.
Methods and Findings
We assessed the Human Mortality Database and 206,374 patients receiving hemodialysis from 12 countries (Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the UK, and the US) participating in the international, prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) between June 1996 and March 2012. Among 35,964 sampled DOPPS patients with full data collection, we studied patient characteristics (descriptively) and mortality (via Cox regression) by sex. In all age groups, more men than women were on hemodialysis (59% versus 41% overall), with large differences observed between countries. The average estimated glomerular filtration rate at hemodialysis initiation was higher in men than women. The male-to-female mortality rate ratio in the general population varied from 1.5 to 2.6 for age groups <75 y, but in hemodialysis patients was close to one. Compared to women, men were younger (mean = 61.9±standard deviation 14.6 versus 63.1±14.5 y), were less frequently obese, were more frequently married and recipients of a kidney transplant, more frequently had coronary artery disease, and were less frequently depressed. Interaction analyses showed that the mortality risk associated with several comorbidities and hemodialysis catheter use was lower for men (hazard ratio [HR] = 1.11) than women (HR = 1.33, interaction p<0.001). This study is limited by its inability to establish causality for the observed sex-specific differences and does not provide information about patients not treated with dialysis or dying prior to a planned start of dialysis.
Women's survival advantage was markedly diminished in hemodialysis patients. The finding that fewer women than men were being treated with dialysis for end-stage renal disease merits detailed further study, as the large discrepancies in sex-specific hemodialysis prevalence by country and age group are likely explained by factors beyond biology. Modifiable variables, such as catheter use, showing significant sex interactions suggest interventional targeting.
Please see later in the article for the Editors' Summary
Editors' Summary
Throughout life, the kidneys filter waste products (from the normal breakdown of tissues and from food) and excess water from the blood to make urine. Chronic kidney disease—an increasingly common condition globally—gradually destroys the kidney's filtration units (the nephrons). As the nephrons stop working, the rate at which the blood is filtered (the glomerular filtration rate) decreases, and waste products build up in the blood, eventually leading to life-threatening end-stage kidney (renal) disease. Symptoms of chronic kidney disease, which rarely occur until the disease is advanced, include tiredness, swollen feet and ankles, and frequent urination, particularly at night. Chronic kidney disease cannot be cured, but its progression can be slowed by controlling diabetes and other conditions that contribute to its development. End-stage kidney disease is treated by regular hemodialysis (a process in which blood is cleaned by passing it through a filtration machine) or by kidney transplantation.
Why Was This Study Done?
Like many other long-term conditions, the prevalence (the proportion of the population that has a specific disease) of chronic kidney disease and of end-stage renal disease, and treatment outcomes for these conditions, may differ between men and women. Some of these sex-specific differences may arise because of sex-specific differences in normal biological functions. Other sex-specific differences may be related to sex-specific differences in patient care or in patient awareness of chronic kidney disease. A comprehensive analysis of sex-specific differences among individuals with end-stage renal disease might identify both treatment inequalities and ways to improve sex-specific care. Here, in the Dialysis Outcomes and Practice Patterns Study (DOPPS), the researchers investigate sex-specific differences in the prevalence and practices of hemodialysis and in the characteristics of patients undergoing hemodialysis, and investigate the adult male-to-female mortality (death) rate among patients undergoing hemodialysis. The DOPPS is a prospective cohort study that is investigating the characteristics, treatment, and outcomes of adult patients undergoing hemodialysis in representative facilities in 19 countries (12 countries were available for analysis at the time of the current study).
What Did the Researchers Do and Find?
To investigate sex-specific differences in hemodialysis prevalence, the researchers compared data from the Human Mortality Database, which provides detailed population and mortality data for 37 countries, with data collected by the DOPPS. Forty-one percent of DOPPS patients were women, compared to 52% of the general population in 12 of the DOPPS countries. Next, the researchers used data collected from a randomly selected subgroup of patients to examine sex-specific differences in patient characteristics and mortality. The average estimated glomerular filtration rate at hemodialysis initiation was higher in men than women. Moreover, men were more frequently recipients of a kidney transplant than women. Notably, although in the general population in a given age group women were less likely to die than men, among hemodialysis patients, women were as likely to die as men. Finally, the researchers investigated which patient characteristics were associated with the largest sex-specific differences in mortality risk. The use of a hemodialysis catheter (a tube that is inserted into a patient's vein to transfer their blood into the hemodialysis machine) was associated with a lower mortality risk in men than in women.
What Do These Findings Mean?
These findings show that, among patients treated with hemodialysis for end-stage renal disease, women differ from men in many ways. Although some of these sex-specific differences may be related to biology, others may be related to patient care and to patient awareness of chronic kidney disease. Because this is an observational study, these findings cannot prove that the reported differences in hemodialysis prevalence, treatment, and mortality are actually caused by being a man or a woman. Importantly, however, these findings suggest that hemodialysis may abolish the survival advantage that women have over men in the general population and that fewer women than men are being treated for end-stage-renal disease, even though chronic kidney disease is more common in women than in men. Finally, the finding that the use of hemodialysis catheters for access to veins is associated with a higher mortality risk among women than among men suggests that, where possible, women should be offered a surgical process called arteriovenous fistula placement, which is recommended for access to veins during long-term hemodialysis but which may, in the past, have been underused in women.
Additional Information
Please access these websites via the online version of this summary at
More information about the DOPPS program is available
The US National Kidney and Urologic Diseases Information Clearinghouse provides information about all aspects of kidney disease; the US National Kidney Disease Education Program provides resources to help improve the understanding, detection, and management of kidney disease (in English and Spanish)
The UK National Health Service Choices website provides information for patients on chronic kidney disease and about hemodialysis, including some personal stories
The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease and about hemodialysis (in English and Spanish)
The not-for-profit UK National Kidney Federation provides support and information for patients with kidney disease and for their carers, including information and personal stories about hemodialysis
World Kidney Day, a joint initiative between the International Society of Nephrology and the International Federation of Kidney Foundations, aims to raise awareness about kidneys and kidney disease
MedlinePlus has pages about chronic kidney disease and about hemodialysis
PMCID: PMC4211675  PMID: 25350533
7.  Association of gender with outcomes in critically ill patients 
Critical Care  2012;16(3):R92.
The influence of gender on mortality and other outcomes of critically ill patients is not clear. Different studies have been performed in various settings and patient populations often yielding conflicting results. We wanted to assess the relationship of gender and intensive care unit (ICU) outcomes in the patients included in the Acute Physiology and Chronic Health Evaluation (APACHE) IV database (Cerner Corporation, USA).
We performed a retrospective review of the data available in the APACHE IV database. A total of 261,255 consecutive patients admitted to adult ICUs in United States from 1 January 2004 to 31 December 2008 were included. Readmissions were excluded from the analysis. The primary objective of the study was to assess the relationship of gender with ICU mortality. The secondary objective was to evaluate the association of gender with active therapy, mechanical ventilation, length of stay in the ICU, readmission rate and hospital mortality. The gender-related outcomes for disease subgroups including acute coronary syndrome, coronary artery bypass graft (CABG) surgery, sepsis, trauma and chronic obstructive pulmonary disease (COPD) exacerbation were assessed as well.
ICU mortality was 7.2% for men and 7.9% for women, odds ratio (OR) for death for women was 1.07 (95% confidence interval (CI): 1.04 to 1.1). There was a statistically significant interaction between gender and age. In patients <50 years of age, women had a reduced ICU mortality compared with men, after adjustment for acute physiology score, ethnicity, co-morbid conditions, pre-ICU length of stay, pre-ICU location and hospital teaching status (adjusted OR 0.83, 95% CI: 0.76 to 0.91). But among patients ≥50 years of age, there was no significant difference in ICU mortality between men and women (adjusted OR 1.02, 95% CI: 0.98 to 1.06).
A higher proportion of men received mechanical ventilation, emergent surgery, thrombolytic therapy and CABG surgery. Men had a higher readmission rate and longer length of ICU stay. The adjusted mortality of women compared to men was higher with CABG, while it was lower with COPD exacerbation. There was no significant difference in mortality in acute coronary syndrome, sepsis and trauma.
Among the critically ill patients, women less than 50 years of age had a lower ICU mortality compared to men, while 50 years of age or older women did not have a significant difference compared to men. Women had a higher mortality compared to men after CABG surgery and lower mortality with COPD exacerbation. There was no difference in mortality in acute coronary syndrome, sepsis or trauma.
PMCID: PMC3580638  PMID: 22617003
8.  Do clinical factors explain persistent sex disparities in the use of acute reperfusion therapy in STEMI in Sweden and Canada? 
This study examined clinical factors associated with sex differences in the use of acute reperfusion therapy (fibrinolysis or primary percutaneous coronary intervention) in ST-elevation myocardial infarction (STEMI) patients, and the interaction between sex and these factors in Sweden and Canada.
Patients with STEMI in Sweden (n=32,676 from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) were compared with similar patients in Canada (n=3375 from the Canadian Global Registry of Acute Coronary Events) for the period 2004–2008.
Unadjusted vs. age-adjusted odds ratios (OR) for no reperfusion (women vs. men) were for Sweden 1.57 (95% CI 1.49–1.64) vs. 1.14 (95% CI 1.08–1.20), and for Canada 1.61 (95% CI 1.39–1.87) vs. OR 1.18 (95% CI 1.01–1.39). Sex differences persisted after multivariable adjustments (including prehospital delay, atypical symptoms, diabetes), factors for which no interaction with sex was found. Among women <60 years, adjusting for atypical symptoms in Canada and angiographic data in Sweden made the greatest contribution to explaining observed sex differences.
In both countries, acute reperfusion therapy in STEMI was used less often in women than in men. Factors associated with these sex differences appear to differ between older and younger women. Targeted interventions are needed to optimize care for women with STEMI, as well as sex- and age-stratified reporting of quality indicators to assess their effectiveness.
PMCID: PMC3821828  PMID: 24338294
Myocardial infarction; reperfusion therapy; sex differences
9.  Threshold Haemoglobin Levels and the Prognosis of Stable Coronary Disease: Two New Cohorts and a Systematic Review and Meta-Analysis 
PLoS Medicine  2011;8(5):e1000439.
Anoop Shah and colleagues performed a retrospective cohort study and a systematic review, and show evidence that in people with stable coronary disease there were threshold hemoglobin values below which mortality increased in a graded, continuous fashion.
Low haemoglobin concentration has been associated with adverse prognosis in patients with angina and myocardial infarction (MI), but the strength and shape of the association and the presence of any threshold has not been precisely evaluated.
Methods and findings
A retrospective cohort study was carried out using the UK General Practice Research Database. 20,131 people with a new diagnosis of stable angina and no previous acute coronary syndrome, and 14,171 people with first MI who survived for at least 7 days were followed up for a mean of 3.2 years. Using semi-parametric Cox regression and multiple adjustment, there was evidence of threshold haemoglobin values below which mortality increased in a graded continuous fashion. For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2–13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76–2.29) compared to those with haemoglobin values in the lowest risk range. Women tended to have lower threshold haemoglobin values (e.g, for MI 12.8 g/dl; 95% CI 12.1–13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI. We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk.
There is an association between low haemoglobin concentration and increased mortality. A large proportion of patients with coronary disease have haemoglobin concentrations below the thresholds of risk defined here. Intervention trials would clarify whether increasing the haemoglobin concentration reduces mortality.
Please see later in the article for the Editors' Summary
Editors' Summary
Coronary artery disease is the main cause of death in high-income countries and the second most common cause of death in middle- and low-income countries, accounting for 16.3%, 13.9%, and 9.4% of all deaths, respectively, in 2004. Many risks factors, such as high blood pressure and high blood cholesterol level, are known to be associated with coronary artery disease, and prevention and treatment of such factors remains one of the key strategies in the management of coronary artery disease. Recent studies have suggested that low hemoglobin may be associated with mortality in patients with coronary artery disease. Therefore, using blood hemoglobin level as a prognostic biomarker for patients with stable coronary artery disease may be of potential benefit especially as measurement of hemoglobin is almost universal in such patients and there are available interventions that effectively increase hemoglobin concentration.
Why was This Study Done?
Much more needs to be understood about the relationship between low hemoglobin and coronary artery disease before hemoglobin levels can potentially be used as a clinical prognostic biomarker. Previous studies have been limited in their ability to describe the shape of this relationship—which means that it is uncertain whether there is a “best” hemoglobin threshold or a continuous graded relationship from “good” to “bad”—to assess gender differences, and to compare patients with angina or who have experienced previous myocardial infarction. In order to inform these knowledge gaps, the researchers conducted a retrospective analysis of patients from a prospective observational cohort as well as a systematic review and meta-analysis (statistical analysis) of previous studies.
What Did the Researchers Do and Find?
The researchers conducted a systematic review and meta-analysis of previous studies and found ten relevant studies, but none evaluated thresholds of risk, only linear relationships.
The researchers carried out a new study using the UK's General Practice Research Database—a national research tool that uses anonymized electronic clinical records of a representative sample of the UK population, with details of consultations, diagnoses, referrals, prescriptions, and test results—as the basis for their analysis. They identified and collected information from two cohorts of patients: those with new onset stable angina and no previous acute coronary syndrome; and those with a first myocardial infarction (heart attack). For these patients, the researchers also looked at all values of routinely recorded blood parameters (including hemoglobin) and information on established cardiovascular risk factors, such as smoking. The researchers followed up patients using death of any cause as a primary endpoint and put this data into a statistical model to identify upper and lower thresholds of an optimal hemoglobin range beyond which mortality risk increased.
The researchers found that there was a threshold hemoglobin value below which mortality continuously increased in a graded manner. For men with myocardial infarction, the threshold value was 13.5 g/dl: 29.5% of patients had hemoglobin below this threshold and had a hazard ratio for mortality of 2.00 compared to those with hemoglobin values in the lowest risk range. Women had a lower threshold hemoglobin value than men: 12.8 g/dl for women with myocardial infarction, but the shape and strength of association did not differ between the genders, or between patients with angina and myocardial infarction.
What Do These Findings Mean?
These findings suggest that there are thresholds of hemoglobin that are associated with increased risk of mortality in patients with angina or myocardial infarction. A substantial proportion of patients (15%–30%) have a hemoglobin level that places them at markedly higher risk of death compared to patients with lowest risk hemoglobin levels and importantly, these thresholds are higher than clinicians might anticipate—and are remarkably similar to World Health Organization anemia thresholds of 12 g/dl for women and 13 g/dl for men. Despite the limitations of these observational findings, this study supports the rationale for conducting future randomized controlled trials to assess whether hemoglobin levels are causal and whether clinicians should intervene to increase hemoglobin levels, for example by oral iron supplementation.
Additional Information
Please access these Web sites via the online version of this summary at
Wikipedia provides information about hemoglobin (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The World Health Organization provides an overview of the global prevalence of coronary artery disease, a factsheet on the top ten causes of death, as well as information on anemia
PMCID: PMC3104976  PMID: 21655315
10.  Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes 
Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sex-related differences at an earlier point in care — presentation to the emergency department.
We collected data on ambulatory care and hospital admissions for 54 134 patients (44% women) who presented to an emergency department in Alberta between July 1998 and March 2001 because of acute myocardial infarction, unstable angina, stable angina or chest pain. We used logistic regression and Cox regression analyses to determine sex-specific associations between the likelihood of discharge from the emergency department or coronary revascularization within 1 year and 1-year mortality after adjusting for age, comorbidities and socioeconomic factors.
Following the emergency department visit, 91.3% of patients with acute myocardial infarction, 87.4% of those with unstable angina, 40.7% of those with stable angina and 19.8% of those with chest pain were admitted to hospital. Women were more likely than men to be discharged from the emergency department: adjusted odds ratio (and 95% confidence interval [CI]) 2.25 (1.75–2.90) for acute myocardial infarction, 1.71 (1.45–2.01) for unstable angina, 1.33 (1.15–1.53) for stable angina and 1.46 (1.36–1.57) for chest pain. Women were less likely than men to undergo coronary revascularization within 1 year: adjusted odds ratio (and 95% CI) 0.65 (0.57–0.73) for myocardial infarction, 0.39 (0.35–0.44) for unstable angina, 0.35 (0.29–0.42) for stable angina and 0.32 (0.27–0.37) for chest pain. Female sex had no impact on 1-year mortality among patients with acute myocardial infarction; it was associated with a decreased 1-year mortality among patients with unstable angina, stable angina and chest pain: adjusted hazard ratio (and 95% CI) 0.60 (0.46–0.78), 0.60 (0.46–0.78) and 0.74 (0.63–0.87) respectively.
Women presenting to the emergency department with coronary syndromes are less likely than men to be admitted to an acute care hospital and to receive coronary revascularization procedures. These differences do not translate into worse outcomes for women in terms of 1-year mortality.
PMCID: PMC2043078  PMID: 17984470
11.  Association of Race and Sex With Risk of Incident Acute Coronary Heart Disease Events 
It is unknown whether long-standing disparities in incidence of coronary heart disease (CHD) among US blacks and whites persist.
To examine incident CHD by black and white race and by sex.
Prospective cohort study of 24 443 participants without CHD at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, who resided in the continental United States and were enrolled between 2003 and 2007 with follow-up through December 31, 2009.
Expert-adjudicated total (fatal and nonfatal) CHD, fatal CHD, and nonfatal CHD (definite or probable myocardial infarction [MI]; very small non–ST-elevation MI [NSTEMI] had peak troponin level <0.5 µg/L).
Over a mean (SD) of 4.2 (1.5) years of follow-up, 659 incident CHD events occurred (153 in black men, 138 in black women, 254 in white men, and 114 in white women). Among men, the age-standardized incidence rate per 1000 person-years for total CHD was 9.0 (95% CI, 7.5–10.8) for blacks vs 8.1 (95% CI, 6.9–9.4) for whites; fatal CHD: 4.0 (95% CI, 2.9–5.3) vs 1.9 (95% CI, 1.4–2.6), respectively; and nonfatal CHD: 4.9 (95% CI, 3.8–6.2) vs 6.2 (95% CI, 5.2–7.4). Among women, the age-standardized incidence rate per 1000 person-years for total CHD was 5.0 (95% CI, 4.2–6.1) for blacks vs 3.4 (95% CI, 2.8–4.2) for whites; fatal CHD: 2.0 (95% CI, 1.5–2.7) vs 1.0 (95% CI, 0.7–1.5), respectively; and nonfatal CHD: 2.8 (95% CI, 2.2–3.7) vs 2.2 (95% CI, 1.7–2.9). Age- and region-adjusted hazard ratios for fatal CHD among blacks vs whites was near 2.0 for both men and women and became statistically nonsignificant after multivariable adjustment. The multivariable-adjusted hazard ratio for incident nonfatal CHD for blacks vs whites was 0.68 (95% CI, 0.51–0.91) for men and 0.81 (95% CI, 0.58–1.15) for women. Of the 444 nonfatal CHD events, 139 participants (31.3%) had very small NSTEMIs.
The higher risk of fatal CHD among blacks compared with whites was associated with cardiovascular disease risk factor burden. These relationships may differ by sex.
PMCID: PMC3772637  PMID: 23117777
coronary heart disease; epidemiology; racial disparities; disease incidence; cohort study
12.  Soluble ST2 and Interleukin-33 Levels in Coronary Artery Disease: Relation to Disease Activity and Adverse Outcome 
PLoS ONE  2014;9(4):e95055.
ST2 is a receptor for interleukin (IL)-33. We investigated an association of soluble ST2 (sST2) and IL-33 serum levels with different clinical stages of coronary artery disease. We assessed the predictive value of sST2 and IL-33 in patients with stable angina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI).
We included 373 patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients were followed for a mean of 43 months. The control group consisted of 65 individuals without significant stenosis on coronary angiography. Serum levels of sST2 and IL-33 were measured by ELISAs.
sST2 levels were significantly increased in patients with STEMI as compared to patients with NSTEMI and stable angina as well as with controls. IL-33 levels did not differ between the four groups. During follow-up, 37 (10%) patients died and the combined endpoint (all cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%) patients. sST2 serum levels significantly predicted mortality in the total cohort. When patients were stratified according to their clinical presentation, the highest quintile of sST2 significantly predicted mortality in patients with STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a significant predictor for the combined endpoint in STEMI patients and in patients with stable angina. Serum levels of IL-33 were not associated with clinical outcome in the total cohort, but the highest quintile of IL-33 predicted mortality in patients with STEMI.
Serum levels of sST2 are increased in patients with acute coronary syndromes as compared to levels in patients with stable coronary artery disease and in individuals without coronary artery disease. sST2 and IL-33 were associated with mortality in patients with STEMI but not in patients with NSTEMI or stable angina.
PMCID: PMC3994012  PMID: 24751794
13.  Trends in and disparities for acute myocardial infarction: an analysis of Medicare claims data from 1992 to 2010 
BMC Medicine  2014;12(1):190.
It is unknown whether previously reported disparities for acute myocardial infarction (AMI) by race and sex have declined over time.
We used Medicare Part A administrative data files for 1992 to 2010 to evaluate changes in per-capita hospitalization rates for AMI, rates of revascularization (percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)), and 30-day mortality for four distinct patient subcohorts: black women; black men; white women; and white men, adjusted for age, comorbidities and year using logistic regression.
The study sample consisted of 4,045,267 AMI admissions between the years 1992 and 2010 (166,660 black women; 116,201 black men; 1,870,816 white women; 1,891,590 white men). AMI hospitalization rates differed significantly in 1992 to 1993 among black women (61.6 hospitalizations per 10,000 Medicare enrollees), black men (73.2 hospitalizations), white women (72.0 hospitalizations) and white men (113.2 hospitalizations) (P <0.0001). By 2009 to 2010 AMI hospitalization rates had declined substantially in all cohorts but disparities remained with significantly lower hospitalization rates among women and blacks compared to men and whites, respectively (P <0.0001). In multivariable-adjusted analyses, despite narrowing of the differences between cohorts over time, disparities in AMI hospitalization rates by race and sex remained statistically significant in 2009 to 2010 (P <0.001). In 1992 to 1993 and 2009 to 2010, rates of PCI within 30-days of AMI differed significantly among black women (8.6% in 1992 to 1993; 24.2% in 2009 to 2010), black men (10.4% and 32.6%), white women (12.8% and 30.5%), and white men (16.1% and 40.7%) (P <0.0001). In multivariable-adjusted analyses, racial disparities in procedure utilization appeared somewhat larger and sex-based disparities remained significant. Unadjusted 30-day mortality after AMI in 1992 to 1993 for black women, black men, white women and white men was 20.4%, 17.9%, 23.1% and 19.5%, respectively (P <0.0001); in 2009 to 2010 mortality was 17.1%, 15.3%, 18.2% and 16.2%, respectively (P <0.0001). In adjusted analyses, racial differences in mortality declined over time but differences by sex (higher mortality for women) persisted.
Disparities in AMI have declined modestly, but remain a problem, particularly with respect to patient sex.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0190-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4212130  PMID: 25341547
Myocardial infarction; MI; Disparity; Outcomes; Race; Sex; Mortality; PCI; Hospitalization rates
14.  Elderly Women Have Lower Rates of Stroke, Cardiovascular Events, and Mortality Following Hospitalization for TIA 
Background and Purpose
TIA patients are at increased risk for stroke, cardiovascular events, and death, yet little is known about whether these risks differ for men and women. We determined whether there are sex-based differences in these outcomes 30-days and one year following TIA using a national sample of elderly patients.
Rates of 30-day and one year hospitalization for TIA (ICD-9 435), stroke (ICD-9 433, 434, 436), coronary artery disease (CAD; ICD-9 410–414), all-cause readmission, and mortality were determined for fee-for-service Medicare patients 65 years of age or older discharged with a TIA in 2002. Cox proportional hazards models and random effects logistic models compared outcomes with risk-adjustment for demographics, medical history, comorbidities, and prior hospitalizations.
The study included 122,063 TIA hospitalizations (mean age 79.0±7.6 years; 62% women; 86% White). Men were younger, but had higher rates of cardiac comorbidities than women. Women had lower unadjusted rates of stroke, CAD, and mortality at 30-days and one year following TIA admission. These relationships persisted in risk-adjusted analyses at 30-days for stroke (HR=0.70, 95% CI 0.64–0.77), CAD (0.86, 0.74–1.00), and mortality (OR=0.74, 0.68–0.82), as well as at one year for stroke (HR=0.85, 0.81–0.89), CAD (0.81, 0.77–0.86), and mortality (OR=0.78, 0.75–0.81).
These data suggest that women have a better prognosis than men within the first year following hospital discharge for a TIA. Additional research is needed to identify factors that may explain these sex-related differences in outcomes.
PMCID: PMC2757938  PMID: 19228857
transient ischemic attack (TIA); outcomes; sex
15.  30-day in-hospital mortality after acute myocardial infarction in Tuscany (Italy): An observational study using hospital discharge data 
Coronary heart disease is the leading cause of mortality in the world. One of the outcome indicators recently used to measure hospital performance is 30-day mortality after acute myocardial infarction (AMI). This indicator has proven to be a valid and reproducible indicator of the appropriateness and effectiveness of the diagnostic and therapeutic process for AMI patients after hospital admission. The aim of this study was to examine the determinants of inter-hospital variability on 30-day in-hospital mortality after AMI in Tuscany. This indicator is a proxy of 30-day mortality that includes only deaths occurred during the index or subsequent hospitalizations.
The study population was identified from hospital discharge records (HDRs) and included all patients with primary or secondary ICD-9-CM codes of AMI (ICD-9 codes 410.xx) that were discharged between January 1, 2009 and November 30, 2009 from any hospital in Tuscany. The outcome of interest was 30-day all-cause in-hospital mortality, defined as a death occurring for any reason in the hospital within 30 days of the admission date. Because of the hierarchical structure of the data, with patients clustered into hospitals, random-effects (multilevel) logistic regression models were used. The models included patient risk factors and random intercepts for each hospital.
The study included 5,832 patients, 61.90% male, with a mean age of 72.38 years. During the study period, 7.99% of patients died within 30 days of admission. The 30-day in-hospital mortality rate was significantly higher among patients with ST segment elevation myocardial infarction (STEMI) compared with those with non-ST segment elevation myocardial infarction (NSTEMI). The multilevel analysis which included only the hospital variance showed a significant inter-hospital variation in 30-day in-hospital mortality. When patient characteristics were added to the model, the hospital variance decreased. The multilevel analysis was then carried out separately in the two strata of patients with STEMI and NSTEMI. In the STEMI group, after adjusting for patient characteristics, some residual inter-hospital variation was found, and was related to the presence of a cardiac catheterisation laboratory.
We have shown that it is possible to use routinely collected administrative data to predict mortality risk and to highlight inter-hospital differences. The distinction between STEMI and NSTEMI proved to be useful to detect organisational characteristics, which affected only the STEMI subgroup.
PMCID: PMC3507800  PMID: 23136904
Myocardial infarction; Mortality; Cardiovascular risk; Medical records
16.  Ethnic variations in female vulnerability after an acute coronary event 
Heart  2004;90(6):621-626.
Objective: To determine the ethnic variation of short and long term female vulnerability after an acute coronary event in a population of Chinese, Indians, and Malays.
Design: Population based registry.
Patients: Residents of Singapore between the ages of 20–64 years with coronary events. Case identification and classification procedures were modified from the MONICA (monitoring trends and determinants in cardiovascular disease) project.
Main outcome measures: Adjusted 28 day case fatality and long term mortality.
Results: From 1991 to 1999, there were 16 320 acute coronary events, including 3497 women. Age adjusted 28 day case fatality was greater in women (51.5% v 38.6%, p < 0.001), with a larger sex difference evident among younger Malay patients. This inequality between the sexes was observed in both the pre-hospitalisation and post-admission periods. Among hospitalised patients, women were older, were less likely to have suffered from a previous Q wave or anterior wall myocardial infarction, and had lower peak creatine kinase concentrations. Case fatality was higher among women, with adjusted hazard ratios of 1.64 (95% confidence interval (CI) 1.43 to 1.88) and 1.50 (95% CI 1.37 to 1.64) for 28 day and mean four year follow up periods. There were significant interactions of sex and age with ethnic group (p  =  0.017). The adjusted hazards for mortality among Chinese, Indian, and Malay women versus men were 1.30, 1.71, and 1.96, respectively. The excess mortality among women diminished with age.
Conclusion: In this multiethnic population, both pre-hospitalisation and post-admission case fatality rates were substantially higher among women. The sex discrepancy in long term mortality was greatest among Malays and in the younger age groups.
PMCID: PMC1768254  PMID: 15145860
case fatality rate; epidemiology; ethnic variations; sex gap; registries
17.  Age-Related Alteration of Risk Profile, Inflammatory Response, and Angiographic Findings in Patients with Acute Coronary Syndrome 
Coronary artery disease (CAD) is a major public health problem which in turn imposes a significant burden on health care systems because of high morbidity and mortality. Although the multifactorial etiology of CAD increases with age, but in recent years, the incidence is increasing among younger age groups.
In this study we aimed to evaluate the effect of age on risk profile, inflammatory response and the angiographic findings in patients with ACS.
Patients and Methods:
The study comprised 253 ACS patients. Seventy six (30%) with UA, 56 (22%) with NSTEMI and 121(48%) with STEMI diagnosis. The value of Hs-CRP, lipid profile, cardiac enzymes, risk factors, EF% and angiographic score were analyzed and compared in different age groups.
Group 1 (n = 68) with age <45 years, group II (n = 110) with age ≥45–<65 years and group III (n = 75) ≥65 years. Group I had more prevalence of male sex, smoking, family history, hypertriglyceridemia and low levels of HDL (P < 0.01), higher incidence of STEMI (P < 0.01) and lower prevalence of UA (P < 0.01). Diabetes mellitus, hypertension, and female gender were more common in older groups. Hs-CRP was significantly lower in the young age (group I). Group I showed a preponderance of single-vessel disease, lower coronary atherosclerotic score and prevalent left anterior descending artery (LAD) involvement compared with older age groups. Hs-CRP was positively correlated to severity of CAD only in older groups. Stepwise multiple regression analysis showed that age, male gender, cardiac enzymes and EF% were common predictors of multivessel disease. Smoking was independent predictor in young patients <45 years while diabetes and Hs-CRP was the key predictor in older patient groups.
Young patients with ACS had different clinical, angiographic and biochemical profile. Hs-CRP peak concentration did not correlate with angiographic findings in young patients that could be attributed to different risk profile and discrete underlying mechanism.
PMCID: PMC2872585  PMID: 20508763
age-Hs-CRP-risk profile; acute coronary syndrome
18.  One-year health status outcomes of unstable angina versus myocardial infarction: a prospective, observational cohort study of ACS survivors 
Unstable angina (UA) patients have lower mortality and reinfarction risks than ST-elevation (STEMI) or non-ST elevation myocardial infarction (NSTEMI) patients and, accordingly, receive less aggressive treatment. Little is known, however, about the health status outcomes (angina, physical function, and quality of life) of UA versus MI patients among survivors of an ACS hospitalization.
In a cohort of 1,192 consecutively enrolled ACS survivors from two Kansas City hospitals, we evaluated the associations between ACS presentation (UA, NSTEMI, and STEMI) and one-year health status (angina, physical functioning and quality of life), one-year cardiac rehospitalization rates, and two-year mortality outcomes, using multivariable regression modeling.
After multivariable adjustment for demographic, hospital, co-morbidity, baseline health status, and treatment characteristics, UA patients had a greater prevalence of angina at 1 year than STEMI patients (adjusted relative risk [RR] = 1.42; 95% CI [1.06, 1.90]) and similar rates as NSTEMI patients (adjusted RR = 1.1; 95% CI [0.85, 1.42]). In addition, UA patients fared no better than MI patients in Short Form-12 physical component scores (UA vs. STEMI score difference -0.05 points; 95% CI [-2.41, 2.3]; UA vs. NSTEMI score difference -1.91 points; 95% CI [-4.01, 0.18]) or Seattle Angina Questionnaire quality of life scores (UA vs. STEMI score difference -1.39 points; 95% CI [-5.63, 2.85]; UA vs. NSTEMI score difference -0.24 points 95% CI [-4.01, 3.54]). Finally, UA patients had similar rehospitalization rates as MI patients (UA vs. STEMI adjusted hazard ratio [HR] = 1.31; 95% CI [0.86, 1.99]; UA vs. NSTEMI adjusted HR = 1.03; 95% CI [0.73, 1.47]), despite better 2-year survival (UA vs. STEMI adjusted HR = 0.51; 95% confidence interval (CI) [0.28, 0.95]; UA vs. NSTEMI adjusted HR = 0.40; 95% CI [0.24, 0.65]).
Although UA patients have better survival rates, they have similar or worse one-year health status outcomes and cardiac rehospitalization rates as compared with MI patients. Clinicians should be aware of the adverse health status outcome risks for UA patients and consider close monitoring for the opportunity to improve their health status and minimize the need for subsequent rehospitalization.
PMCID: PMC2014769  PMID: 17850662
19.  Sex related differences in short and long-term prognosis after acute myocardial infarction: 10 year follow up of 3073 patients in database of first Danish Verapamil Infarction Trial. 
BMJ : British Medical Journal  1996;313(7050):137-140.
OBJECTIVE--To re-examine the prevailing hypothesis that women fare worse than men after acute myocardial infarction. DESIGN--10 year follow up of all patients with confirmed acute myocardial infarction registered in the database of the Danish verapamil infarction trial in 1979-81. SETTING--16 coronary care units, covering a fifth of the total Danish population. PATIENTS--3073 consecutive patients with acute myocardial infarction, 738 (24%) women and 2335 (76%) men. MAIN OUTCOME MEASURES--Early mortality (before day 15). For patients alive on day 15: mortality, cause of death, admission with recurrent infarction, and mortality after reinfarction. RESULTS--Early mortality increased significantly with age (P < 0.0001) but was not significantly related to sex, with a 15 day mortality of 17% in women and 16% in men. Adjustment for age and sex simultaneously revealed a significant interaction (P = 0.02) between these variables, with a greater increase with age in early mortality for men than for women (early mortality was equal for the two sexes at age 64 years). Ten year mortality in patients alive on day 15 was 58.8%. The overall age adjusted hazard ratio (95% confidence interval) for women versus men was 0.90 (0.80 to 1.01); 0.90 (0.78 to 1.04) for 10 year reinfarction (48.8%); and 0.98 (0.82 to 1.16) for 10 year mortality after reinfarction (82.3%). No difference in cause of death was found between the sexes. With a follow up of up to 10 years for patients alive on day 15 mortality, rate of reinfarction, and mortality after reinfarction increased with increasing age (P < 0.0001). CONCLUSION--Sex by itself is not a risk factor after acute myocardial infarction.
PMCID: PMC2351565  PMID: 8688773
20.  Obesity Indexes and Total Mortality among Elderly Subjects at High Cardiovascular Risk: The PREDIMED Study 
PLoS ONE  2014;9(7):e103246.
Different indexes of regional adiposity have been proposed for identifying persons at higher risk of death. Studies specifically assessing these indexes in large cohorts are scarce. It would also be interesting to know whether a dietary intervention may counterbalance the adverse effects of adiposity on mortality.
We assessed the association of four different anthropometric indexes (waist-to-height ratio (WHtR), waist circumference (WC), body mass index (BMI) and height) with all-cause mortality in 7447 participants at high cardiovascular risk from the PREDIMED trial. Forty three percent of them were men (55 to 80 years) and 57% were women (60 to 80 years). All of them were initially free of cardiovascular disease. The recruitment took place in 11 recruiting centers between 2003 and 2009.
After adjusting for age, sex, smoking, diabetes, hypertension, intervention group, family history of coronary heart disease, and leisure-time physical activity, WC and WHtR were found to be directly associated with a higher mortality after 4.8 years median follow-up. The multivariable-adjusted HRs for mortality of WHtR (cut-off points: 0.60, 0.65, 0.70) were 1.02 (0.78–1.34), 1.30 (0.97–1.75) and 1.55 (1.06–2.26). When we used WC (cut-off points: 100, 105 and 110 cm), the multivariable adjusted Hazard Ratios (HRs) for mortality were 1.18 (0.88–1.59), 1.02 (0.74–1.41) and 1.57 (1.19–2.08). In all analyses, BMI exhibited weaker associations with mortality than WC or WHtR. The direct association between WHtR and overall mortality was consistent within each of the three intervention arms of the trial.
Our study adds further support to a stronger association of abdominal obesity than BMI with total mortality among elderly subjects at high risk of cardiovascular disease. We did not find evidence to support that the PREDIMED intervention was able to counterbalance the harmful effects of increased adiposity on total mortality.
Trial Registration ISRCTN35739639
PMCID: PMC4114489  PMID: 25072784
21.  Mortality in Pharmacologically Treated Older Adults with Diabetes: The Cardiovascular Health Study, 1989–2001 
PLoS Medicine  2006;3(10):e400.
Diabetes mellitus (DM) confers an increased risk of mortality in young and middle-aged individuals and in women. It is uncertain, however, whether excess DM mortality continues beyond age 75 years, is related to type of hypoglycemic therapy, and whether women continue to be disproportionately affected by DM into older age.
Methods and Findings
From the Cardiovascular Health Study, a prospective study of 5,888 adults, we examined 5,372 participants aged 65 y or above without DM (91.2%), 322 with DM treated with oral hypoglycemic agents (OHGAs) (5.5%), and 194 with DM treated with insulin (3.3%). Participants were followed (1989–2001) for total, cardiovascular disease (CVD), coronary heart disease (CHD), and non-CVD/noncancer mortality. Compared with non-DM participants, those treated with OHGAs or insulin had adjusted hazard ratios (HRs) for total mortality of 1.33 (95% confidence interval [CI], 1.10 to 1.62) and 2.04 (95% CI, 1.62 to 2.57); CVD mortality, 1.99 (95% CI, 1.54 to 2.57) and 2.16 (95% CI, 1.54 to 3.03); CHD mortality, 2.47 (95% CI, 1.89 to 3.24) and 2.75 (95% CI, 1.95 to 3.87); and infectious and renal mortality, 1.35 (95% CI, 0.70 to 2.59) and 6.55 (95% CI, 4.18 to 10.26), respectively. The interaction of age (65–74 y versus ≥75 y) with DM was not significant. Women treated with OHGAs had a similar HR for total mortality to men, but a higher HR when treated with insulin.
DM mortality risk remains high among older adults in the current era of medical care. Mortality risk and type of mortality differ between OHGA and insulin treatment. Women treated with insulin therapy have an especially high mortality risk. Given the high absolute CVD mortality in older people, those with DM warrant aggressive CVD risk factor reduction.
The negative impact on mortality of diabetes persists into old age. Elderly people with diabetes might be twice as likely to die from CVD as people without diabetes. More aggressive treatment of CVD risk factors in older patients should be considered.
Editors' Summary
Diabetes is a growing global health problem. By 2030, 300 million people worldwide may have this chronic, incurable disorder, double the current number. People with diabetes have dangerously high amounts of sugar in their blood. Blood-sugar levels are normally controlled by insulin, a hormone made by the pancreas that tells cells to absorb sugar from the blood. This control fails in people with diabetes, either because they make no insulin (type 1 diabetes) or because their cells are insensitive to insulin (type 2 diabetes). Type 1 diabetes is controlled with insulin injections; type 2 diabetes is controlled with diet, exercise, and pills that reduce blood-sugar levels. Long-term complications of diabetes include kidney failure, blindness, and nerve damage. Individuals with diabetes also have an increased risk of developing cardiovascular disease (CVD)—heart problems, strokes, and poor circulation—because of damage to their blood vessels.
Why Was This Study Done?
Epidemiological studies (investigations of disease patterns, causes, and control in populations) have indicated that diabetes increases the risk of death (mortality) from CVD in young and middle-aged people, but it is not known whether this is also true for old people. It is also not known what effect long-term treatment for diabetes has on mortality or whether the risk of death from CVD is decreasing in diabetic people as it is in the general US population. This information would help physicians provide health care and lifestyle advice to people with diabetes. In this study, the researchers have investigated mortality patterns in elderly diabetic people by looking at data collected between 1989 and 2001 by the US Cardiovascular Health Study, an observational study of nearly 6,000 people aged over 65 years (in this type of study participants are observed without imposing any specific changes to their lifestyle, behavior, medical care, or treatments).
What Did the Researchers Do and Find?
Participants were screened at the start of the Cardiovascular Health Study for CVD and diabetes (defined as drug-treated disease), for established CVD risk factors such as high blood pressure and smoking, for recently recognized CVD risk factors (for example, subclinical CVD), and for psychosocial factors associated with diabetes that might influence mortality, such as frailty and depression. At this time, about 5% of the participants were taking oral hypoglycemic agents for diabetes and about 3% were taking insulin. During the 11-year study, 40% of the participants died. After adjusting for CVD risk factors and psychosocial factors, the researchers calculated that people treated with oral hypoglycemic agents were 1.3 times as likely to die from all causes and people treated with insulin were twice as likely to die as people without diabetes. The risk of death from CVD was about twice as high in both groups of diabetic participants as in non-diabetic participants; the risk of death from coronary heart disease was increased about 2.5-fold. These adjusted relative risks are very similar to those found in previous studies. The researchers also report that participants treated with insulin were six times more likely to die from infectious diseases or renal failure than nondiabetic participants, and women treated with insulin had a particularly high mortality risk.
What Do These Findings Mean?
These findings indicate that the negative impact on mortality of diabetes persists into old age and that death from CVD is currently declining in both older diabetic people and nondiabetic people. In addition, they show that diabetic people treated with insulin are at a greater risk of dying relative to people without diabetes and those taking oral hypoglycemic agents. This might reflect the type of diabetes that these people had, but this was not investigated. How long participants had had diabetes was also not considered, nor how many people developed diabetes during the study. These and other limitations might mean that the reported excess mortality due to diabetes is an underestimate. Nevertheless, the estimate that elderly people with diabetes are twice as likely to die from CVD as people without diabetes is important. Many elderly people die anyway because of CVD, so this increased risk represents many more deaths than the similar increased risk in younger diabetic populations. Yet, elderly people often receive less-intensive management of CVD risk factors than younger people. The results of this study suggest that rectifying this situation could prolong the lives of many elderly people with diabetes.
Additional Information.
Please access these Web sites via the online version of this summary at
MedlinePlus encyclopedia has pages on diabetes, heart disease, stroke and poor circulation
The US National Institute of Diabetes and Digestive and Kidney Diseases provides patient information on diabetes
Information for patients on prevention, diagnosis, and management of diabetes is available from the America Diabetes Association
Patient information is available from the American Heart Association on all aspects of heart disease, including its association with diabetes
Wikipedia pages on diabetes and cardiovascular disease (note that Wikipedia is a free online encyclopedia that anyone can edit)
Further information is available about the Cardiovascular Health Study
PMCID: PMC1609124  PMID: 17048978
22.  Does Simplicity Compromise Accuracy in ACS Risk Prediction? A Retrospective Analysis of the TIMI and GRACE Risk Scores 
PLoS ONE  2009;4(11):e7947.
The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems.
Methodology/Principal Findings
ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes.
The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.
PMCID: PMC2776353  PMID: 19956773
23.  Gender differences in management and outcome in non‐ST‐elevation acute coronary syndrome 
Heart  2006;93(11):1357-1362.
To study gender differences in management and outcome in patients with non‐ST‐elevation acute coronary syndrome.
Design, setting and patients
Cohort study of 53 781 consecutive patients (37% women) from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS‐HIA), with a diagnosis of either unstable angina pectoris or non‐ST‐elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 1998 and 2002, and followed for 1 year.
Main outcome measures
Treatment intensity and in‐hospital, 30‐day and 1‐year mortality.
Women were older (73 vs 69 years, p<0.001) and more likely to have a history of hypertension and diabetes, but less likely to have a history of myocardial infarction or revascularisation. After adjustment, there were no major differences in acute pharmacological treatment or prophylactic medication at discharge.
Revascularisation was, however, even after adjustment, performed more often in men (OR 1.15; 95% CI, 1.09 to 1.21). After adjustment, there was no significant difference in in‐hospital (OR 1.03; 95% CI, 0.94 to 1.13) or 30‐days (OR 1.07; 95% CI, 0.99 to 1.15) mortality, but at 1 year being male was associated with higher mortality (OR 1.12; 95% CI, 1.06 to 1.19).
Although women are somewhat less intensively treated, especially regarding invasive procedures, after adjustment for differences in background characteristics, they have better long‐term outcomes than men.
PMCID: PMC2016903  PMID: 17085528
24.  Higher mortality in women after ST-segment elevation myocardial infarction in very young patients 
Data on mortality in young patients with ST-segment elevation myocardial infarction (STEMI) when compared to older people or regarding therapeutic strategies are contradictory. We investigate the prognosis of women under 40 after STEMI in a prospective nationwide acute coronary syndrome registry.
Material and methods
We analyzed all 527 consecutive men and women (12.3% females) aged from 20 to 40 years (mean 35.7 ±4.5) presenting with STEMI, of all 26035 STEMI patients enrolled.
Differences between genders in the major cardiovascular risk factors, clinical presentation, extent of the disease and time to reperfusion were insignificant. The majority of patients (67%) underwent coronary angiography followed by primary percutaneous coronary intervention (PCI) in 79.9% of them. A 92% reperfusion success rate measured by post-procedural TIMI 3 flow was achieved. There were no significant differences between genders in the administration of modern pharmacotherapy both on admission and after discharge from hospital. In-hospital mortality was very low in both genders, but 12-month mortality was significantly higher in women (10.8% vs. 3.0%; p = 0.003). Killip class 3 or 4 on admission (95% CI 19.6-288.4), age per 5-year increase (95% CI 1.01-3.73) and primary PCI (95% CI 0.1-0.93) affected mortality. In patients who underwent reperfusion there was moderately higher mortality in women than in men (7.1% vs. 1.9%; p = 0.046).
Despite little difference in the basic clinical characteristics and the management including a wide use of primary PCI, long-term mortality in women under forty after STEMI is significantly higher than in men.
PMCID: PMC3701974  PMID: 23847662
gender-related difference; ST-segment elevation myocardial infarction; myocardial infarction; mortality; young
25.  Diabetes Mellitus, Hypothalamic Hypoestrogenemia And Coronary Artery Disease In Premenopausal Women (From The NHLBI-Sponsored WISE Study) 
The American journal of cardiology  2008;102(2):150-154.
Diabetes mellitus (DM) portends a higher risk of coronary heart disease mortality in women compared to men. This relationship appears to be independent of traditional cardiac risk factors and the role of reproductive hormones has been postulated. We assessed the relationship between DM, Hypothalamic hypoestrogenemia (HHE), angiographic coronary artery disease (CAD) and major adverse cardiovascular events (MACE) over a median 5.9 years in premenopausal women enrolled in the Women’s Ischemia Syndrome Evaluation (WISE) study. We evaluated 95 premenopausal WISE women who underwent coronary angiography for suspected ischemia and were not taking exogenous reproductive hormones. Results showed that there was no difference in age between women with (n=30) and without (n=65) DM (43±6 yrs). DM was associated with hypertension, HHE, angiographic CAD and coronary artery severity score (CSS) (all p<0.05). Women with DM were twice as likely to have HHE (50% vs. 26% p=0.02) compared to women without DM. Presence of both DM and HHE was associated with increased prevalence (40% vs. 12% or 13%, p=0.006) and severity of angiographic coronary artery disease (CSS 19.9 (19.2) vs. 7.7 (4.6) or 12.3 (18.8), p=0.008) as compared to either HHE or DM alone, respectively. DM was moderately predictive of MACE. In conclusion, among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, DM is associated with HHE. Presence of both DM and HHE predicts greater burden of angiographic CAD. Prospective research is warranted to better understand causal relationships between DM, endogenous hormones, and MACE in premenopausal women.
PMCID: PMC3615899  PMID: 18602512

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