We assessed the effect of previous peripheral arterial disease (PAD) and stroke on clinical outcomes in patients with acute coronary syndrome (ACS) and sought to ascertain the effectiveness of ...evidence-based therapies in these patients. We used data from the multinational Global Registry of Acute Coronary Events. Patients were enrolled at 102 hospitals in 13 countries between April 1999 and September 2005. Patients presenting with ACS were stratified according to the presence of previous PAD, stroke, PAD and stroke, or neither. In-hospital analysis included 48,418 patients and 6-month analysis included 32,735 patients. The primary end point was all-cause mortality and major adverse cardiac events during 6-month follow-up. Adverse in-hospital and 6-month events were lowest in patients with neither PAD nor stroke and highest in patients with PAD and stroke after adjustment for baseline demographics and co-morbidities. In-hospital mortality for the 4 groups (neither, PAD, stroke, PAD and stroke) was 4.5% versus 7.2% versus 8.9% versus 9.4% (p <0.001) and that for 6-month mortality was 3.9% versus 8.8% versus 9.3% versus 12%, and these differences persisted after accounting for differences in baseline characteristics. Use of evidence-based therapies was associated with significantly less morbidity and mortality in all ACS subgroups. In conclusion, outcomes after ACS are worse in patients with PAD or stroke, with the highest risk in patients with the 2 conditions and the use of evidence-based therapies are associated with improved outcomes in all ACS subgroups.
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The incidence, prognosis, and factors associated with ventricular arrhythmia (VA) in acute coronary syndrome are unknown. We sought to examine the magnitude, predictors, and outcomes of in-hospital ...VA in patients with acute coronary syndrome. The population comprised 52,380 patients enrolled in the Global Registry of Acute Coronary Events from 1999 to 2005. The proportion who developed VA during hospitalization was 6.9% (1.8% with ventricular tachycardia, 5.1% with ventricular fibrillation or cardiac arrest). The incidence of in-hospital VA decreased over time (8.0% in 1999, 7.0% in 2002, 5.8% in 2005, p <0.001). In-hospital case-fatality rates were higher in patients with versus those without VA (52% vs 1.6%). Several demographic and clinical variables were associated with the occurrence of VA including ST deviation, Killip class, age, initial cardiac markers, serum creatinine and heart rate, and history of selected co-morbidities. Six-month postdischarge mortality was higher in survivors of in-hospital VA versus those who did not develop VA during hospitalization (odds ratio 1.57, 95% confidence interval 1.27 to 1.95). In conclusion, development of VA during hospitalization for acute coronary syndrome was associated with higher in-hospital and 6-month mortalities.
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It is unclear if clinician risk stratification has changed with time. The aim of this study was to assess the temporal change in the concordance between patient presenting risk and the intensity of ...evidence-based therapies received for non–ST-segment elevation acute coronary syndromes over a 9-year period. Data from 3,562 patients with non–ST-segment elevation acute coronary syndromes enrolled in the Australian and New Zealand population of the Global Registry of Acute Coronary Events (GRACE) from 1999 to 2007 were analyzed. Patients were stratified to risk groups on the basis of the GRACE risk score for in-hospital mortality. Main outcome measures included in-hospital use of widely accepted evidence-based medications, investigations, and procedures. Invasive management was consistently higher in low-risk patients than in intermediate- or high-risk patients (coronary angiography 66.7% vs 63.5% vs 35.3%, p <0.001; percutaneous coronary intervention 31.1% vs 22.0% vs 12.9%, p <0.001). Absolute rates of angiography and percutaneous coronary intervention in the high-risk group remained 24% and 15% lower compared to the low-risk group in the most recent time period (2005 to 2007). In-hospital use of thienopyridine, low–molecular weight heparin, and glycoprotein IIb/IIIa inhibitors showed a similar inverse relation with risk. Prescription of aspirin, β blockers, statins, and angiotensin receptor blockers was inversely related to risk before 2004, although this inverse relation was no longer present in the most recent time period (2005 to 2007). Only in-hospital use of unfractionated heparin showed use concordant with patient risk status. In conclusion, despite an overall increase in the uptake of evidence-based therapies, most investigations and treatments are not targeted on the basis of patient risk. Clinician risk stratification remains suboptimal compared to objective measures of patient risk.
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Summary Background WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously ...reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability. Methods We analysed information about availability and costs of cardiovascular disease medicines (aspirin, β blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry. Findings Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24 776), 33% of lower middle-income countries (13 253 of 40 023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16 874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio OR 0·16, 95% CI 0·04–0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04–0·55). Interpretation Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025. Funding Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.
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Summary Background Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a ...simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries. Methods The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35–70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4·0 years (IQR 2·9–5·1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally. Findings Between January, 2003, and December, 2009, a total of 142 861 participants were enrolled in the PURE study, of whom 139 691 with known vital status were included in the analysis. During a median follow-up of 4·0 years (IQR 2·9–5·1), 3379 (2%) of 139 691 participants died. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1·16, 95% CI 1·13–1·20; p<0·0001), cardiovascular mortality (1·17, 1·11–1·24; p<0·0001), non-cardiovascular mortality (1·17, 1·12–1·21; p<0·0001), myocardial infarction (1·07, 1·02–1·11; p=0·002), and stroke (1·09, 1·05–1·15; p<0·0001). Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure. We found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated (0·916, 0·880–0·953; p<0·0001), but this association was not found in middle-income and low-income countries. Interpretation This study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease. Further research is needed to identify determinants of muscular strength and to test whether improvement in strength reduces mortality and cardiovascular disease. Funding Full funding sources listed at end of paper (see Acknowledgments).
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Summary Background Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors ...for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. Methods We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. Findings Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases 10 388 with ischaemic stroke and 3059 intracerebral haemorrhage and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72–3·28; PAR 47·9%, 99% CI 45·1–50·6), regular physical activity (0·60, 0·52–0·70; 35·8%, 27·7–44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65–2·06 for highest vs lowest tertile; 26·8%, 22·2–31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53–0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index mAHEI; 23·2%, 18·2–28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27–1·64 for highest vs lowest tertile; 18·6%, 13·3–25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78–2·72; 17·4%, 13·1–22·6), current smoking (1·67, 1·49–1·87; 12·4%, 10·2–14·9), cardiac causes (3·17, 2·68–3·75; 9·1%, 8·0–10·2), alcohol consumption (2·09, 1·64–2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4–9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05–1·30; 3·9%, 1·9–7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). Interpretation Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. Funding Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.
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Summary Background Atrial fibrillation is an important cause of morbidity and mortality worldwide, but scant data are available for long-term outcomes in individuals outside North America or Europe, ...especially in primary care settings. Methods We did a cohort study using a prospective registry of patients in 47 countries who presented to a hospital emergency department with atrial fibrillation or atrial flutter as a primary or secondary diagnosis. 15 400 individuals were enrolled to determine the occurrence of death and strokes (the primary outcomes) in this cohort over eight geographical regions (North America, western Europe, and Australia; South America; eastern Europe; the Middle East and Mediterranean crescent; sub-Saharan Africa; India; China; and southeast Asia) 1 year after attending the emergency department. Patients from North America, western Europe, and Australia were used as the reference population, and compared with patients from the other seven regions Findings Between Dec 24, 2007, and Oct 21, 2011, we enrolled 15 400 individuals to the registry. Follow-up was complete for 15 361 (99·7%), of whom 1758 (11%) died within 1 year. Fewer deaths occurred among patients presenting to the emergency department with a primary diagnosis of atrial fibrillation compared with patients who had atrial fibrillation as a secondary diagnosis (377 6% of 6825 patients vs 1381 16% of 8536, p<0·0001). Twice as many patients had died by 1 year in South America (192 17% of 1132) and Africa (225 20% of 1137) compared with North America, western Europe, and Australia (366 10% of 3800, p<0·0001). Heart failure was the most common cause of death (519 30% of 1758); stroke caused 148 (8%) deaths. 604 (4%) of 15361 patients had had a stroke by 1 year; 170 (3%) of 6825 for whom atrial fibrillation was a primary diagnosis and 434 (5%) of 8536 for whom it was a secondary diagnosis (p<0·0001). The highest number of strokes occurred in patients in Africa (89 8% of 1137), China (143 7% of 2023), and southeast Asia (88 7% of 1331) and the lowest occurred in India (20 <1% of 2536). 94 (3%) of 3800 patients in North America, western Europe, and Australia had a stroke. Interpretation Marked unexplained inter-regional variations in the occurrence of stroke and mortality suggest that factors other than clinical variables might be important. Prevention of death from heart failure should be a major priority in the treatment of atrial fibrillation. Funding Boehringer Ingelheim.
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Summary Background Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses ...and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. Methods The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00427388. Findings Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared with placebo, did not reduce the risk of death at 30 days (154 4% vs 177 5% patients; relative risk RR 0·87, 95% CI 0·70–1·07, p=0·19) or the risk of death or major morbidity (909 24% vs 885 24%; RR 1·03, 95% CI 0·95–1·11, p=0·52). The most common safety outcomes in the methylprednisolone and placebo group were infection (465 12% vs 493 13%), surgical site infection (151 4% vs 151 4%), and delirium (295 8% vs 289 8%). Interpretation Methylprednisolone did not have a significant effect on mortality or major morbidity after cardiac surgery with cardiopulmonary bypass. The SIRS trial does not support the routine use of methylprednisolone for patients undergoing cardiopulmonary bypass. Funding Canadian Institutes of Health Research.
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Summary Background Alcohol consumption is proposed to be the third most important modifiable risk factor for death and disability. However, alcohol consumption has been associated with both benefits ...and harms, and previous studies were mostly done in high-income countries. We investigated associations between alcohol consumption and outcomes in a prospective cohort of countries at different economic levels in five continents. Methods We included information from 12 countries participating in the Prospective Urban Rural Epidemiological (PURE) study, a prospective cohort study of individuals aged 35–70 years. We used Cox proportional hazards regression to study associations with mortality (n=2723), cardiovascular disease (n=2742), myocardial infarction (n=979), stroke (n=817), alcohol-related cancer (n=764), injury (n=824), admission to hospital (n=8786), and for a composite of these outcomes (n=11 963). Findings We included 114 970 adults, of whom 12 904 (11%) were from high-income countries (HICs), 24 408 (21%) were from upper-middle-income countries (UMICs), 48 845 (43%) were from lower-middle-income countries (LMICs), and 28 813 (25%) were from low-income countries (LICs). Median follow-up was 4·3 years (IQR 3·0–6·0). Current drinking was reported by 36 030 (31%) individuals, and was associated with reduced myocardial infarction (hazard ratio HR 0·76 95% CI 0·63–0·93), but increased alcohol-related cancers (HR 1·51 1·22–1·89) and injury (HR 1·29 1·04–1·61). High intake was associated with increased mortality (HR 1·31 1·04–1·66). Compared with never drinkers, we identified significantly reduced hazards for the composite outcome for current drinkers in HICs and UMICs (HR 0·84 0·77–0·92), but not in LMICs and LICs, for which we identified no reductions in this outcome (HR 1·07 0·95–1·21; pinteraction <0·0001). Interpretation Current alcohol consumption had differing associations by clinical outcome, and differing associations by income region. However, we identified sufficient commonalities to support global health strategies and national initiatives to reduce harmful alcohol use. Funding Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.
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Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between ...cardiovascular disease and common measures of socioeconomic status—wealth and education—differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management.
In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family.
Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96–1·58) for high-income countries, 1·59 (1·42–1·78) in middle-income countries, and 2·23 (1·79–2·77) in low-income countries (pinteraction<0·0001). We observed similar results for all-cause mortality, with HRs of 1·50 (1·14–1·98) for high-income countries, 1·80 (1·58–2·06) in middle-income countries, and 2·76 (2·29–3·31) in low-income countries (pinteraction<0·0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (pinteraction<0·0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries.
Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education.
Full funding sources are listed at the end of the paper (see Acknowledgments).
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