Examinando por Autor "Joseph, Philip"

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    Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis
    (The Lancet, 2021-09-25) Joseph, Philip; Roshandel, Gholamreza; Gao, Peggy; Pais, Prem; Lonn, Eva; Xavier, Denis; Avezum, Alvaro; Zhu, Jun; Liu, Lisheng; Sliwa, Karen; Gamra, Habib; Bangdiwala, Shrikant I.; Teo, Koon; Diaz, Rafael; Dans, Antonio; Lopez-Jaramillo, Patricio; Prabhakaran, Dorairaj; Castellano, Jose Maria; Fuster, Valentin; Rodgers, Anthony; Huffman, Mark D.; Bosch, Jackie; Dagenais, Gilles R.; Malekzadeh, Reza; Yusuf, Salim; Polypill Trialists' Collaboration; Masira
    Background In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown. Methods We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies. Findings Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53–0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38–0·70), revascularisation (0·54, 0·36–0·80), stroke (0·59, 0·45–0·78), and cardiovascular death (0·65, 0·52–0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001). Interpretation Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors.
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    Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153 152 middle-aged individuals
    (Oxford Academic, 2021-06-05) Joseph, Philip; Healey, Jeffrey S.; Raina, Parminder; Connolly, Stuart J.; Ibrahim, Quazi; Gupta, Rajeev; Avezum, Alvaro; Dans, Antonio; Lopez-Jaramillo, Patricio; Yeates, Karen; Teo, Koon; Douma, Reuben; Bahonar, Ahmad; Chifamba, Jephat; Lanas, Fernando; Dagenais, Gilles R.; Lear, Scott; Kumar, Rajesh; Kengne, Andre P.; Keskinler, Mirac; Mohan, Viswanathan; Mony, Prem; Alhabib, Khalid F.; Huisman, Hugo; Iype, Thomas; Zatonska, Katarzyna; Ismail, Rosnah; Kazmi, Khawar; Rosengren, Annika; Rahman, Omar; Yusufali, Afzalhussein; Wei, Li; Orlandini, Andres; Islam, Shofiqul; Rangarajan, Sumathy; Yusuf, Salim; The PURE Investigators; Masira
    Aims To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine antithrombotic use and clinical outcomes. Methods and results Baseline ECGs were collected in 153 152 middle-aged participants (ages 35–70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow-up of 7.4 years) were available in one cohort. Cross-sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China, and Southeast Asia (270–360 cases per 100 000 persons); and lowest in the Middle East, Africa, and South Asia (30–60 cases per 100 000 persons) (P < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs) (P < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received antithrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke [hazard ratio (HR) 2.29; 95% confidence interval (CI) 1.49–3.52] and death (HR 2.97; 95% CI 2.25–3.93); with similar rates in different countries grouped by income level. Conclusions Large variations in AF prevalence occur in different regions and countries grouped by income level, but this is only partially explained by traditional AF risk factors. Antithrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.
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    Health-related quality of life and mortality in heart failure. The global congestive heart failure study of 23000 patients from 40 countries
    (American Heart Association, Inc., 2021-04-28) Johansson, Isabelle; Joseph, Philip; Balasubramanian, Kumar; McMurray, John J.V.; Lund, Lars H.; Ezekowitz, Justin A.; Kamath, Deepak; Alhabib, Khalid; Bayes-Genis, Antoni; Budaj, Andrzej; Dans, Antonio; Dzudie, Anastase; Probstfield, Jefferey L.; Fox, Keith A.; Karaye, Kamilu M.; Makubi, Abel; Fukakusa, Bianca; Teo, Koon; Temizhan, Ahmet; Wittlinger, Thomas; Maggioni, Aldo P.; Lanas, Fernando; Lopez-Jaramillo, Patricio; Silva-Cardoso, José; Sliwa, Karen; Dokainish, Hisham; Grinvalds, Alex; McCready, Tara; Yusuf, Salim; G-CHF Investigators; Masira
    Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries. Methods: We used the Kansas City Cardiomyopathy Questionnaire–12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years. Results: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score decrement was 1.18 (95% CI, 1.17–1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America, and Africa (weakest association in South Asia: HR, 1.08 [95% CI, 1.03–1.14]; strongest association in Eastern Europe: HR, 1.31 [95% CI, 1.21–1.42]; interaction P<0.0001). Lower HRQL predicted death in patients with New York Heart Association class I or II and III or IV symptoms (HR, 1.17 [95% CI, 1.14–1.19] and HR, 1.14 [95% CI, 1.12–1.17]; interaction P=0.13) and was a stronger predictor for the composite outcome in New York Heart Association class I or II versus class III or IV (HR 1.15 [95% CI, 1.13–1.17] versus 1.09 [95% CI, [1.07–1.11]; interaction P<0.0001). HR for death was greater in ejection fraction ≥40 versus <40% (HR, 1.23 [95% CI, 1.20–1.26] and HR, 1.15 [95% CI, 1.13–1.17]; interaction P<0.0001). Conclusion: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF, and among patients with preserved and reduced ejection fraction.
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    The International Polycap Study-3 (TIPS-3) : Design, baseline characteristics and challenges in conduct
    (2018-08-02) Lopez-Jaramillo, Patricio; Joseph, Philip; Pais, Prem; Dans, Antonio; Bosch, Jackie; Xavier, Denis; Yusoff, Khalid; Santoso, Anwar; Talukder, Shamim; Gamra, Habib; Yeates, Karen; Camacho López, Paul Anthony; Tyrwhitt, Jessica; Gao, Peggy; Teo, Koon; Yusuf, Salim
    BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial. METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events. RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk. CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.
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    Long-term Effects of Statins, Blood Pressure-Lowering, and Both on Erectile Function in Persons at Intermediate Risk for Cardiovascular Disease : A Substudy of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) Randomized Controlled Trial
    (2018-01) Joseph, Philip; Lonn, Eva; Bosch, Jackie; Lopez-Jaramillo, Patricio; Zhu, Jun; Keltai, Matyas; Dans, Antonio; Reid, Christopher M.; Khunti, Kamlesh; Toff, William D.; Piegas, Leopoldo S.; Kim, Jae Hyung; Swaminathan, Balakumar; Bohm, Michael; Yusuf, Salim; HOPE-3 Investigators
    Background: It is unclear whether modifying cholesterol, blood pressure, or both affect erectile dysfunction. Also, there are concerns that erectile dysfunction is worsened by common medications used to treat these risk factors. In this study, we evaluated the effect of: (1) cholesterol-lowering with a statin; (2) pharmacologic blood pressure reduction; and (3) their combination, on erectile function. Methods: A priori, this was a secondary analysis of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) randomized controlled trial. Men were 55 years of age or older with at least 1 cardiovascular risk factor. Erectile function was measured using the erectile function domain of the International Index of Erectile Function (IIEF-EF) score. Men with incomplete scores, or who did not engage in sexual activity, were excluded. Using a 2 × 2 factorial design, participants were randomized to rosuvastatin (10 mg/d) or placebo, and to candesartan with hydrochlorothiazide (HCTZ; 16 mg/12.5 mg/d; Cand+HCTZ) or placebo. Primary outcome was change in IIEF-EF from baseline to end of study follow-up. Results: Two thousand one hundred fifty-three men were included; mean age was 61.5 years, and mean follow-up was 5.8 years. Mean IIEF-EF score at baseline was 23.0 (SD 5.6). Least square mean change in the IIEF-EF score did not differ with rosuvastatin compared with placebo (−1.4; standard error [SE], 0.3 vs −1.5; SE, 0.3; P = 0.74), Cand+HCTZ compared with placebo (−1.6; SE, 0.3 vs −1.3; SE, 0.3; P = 0.10), or combination therapy compared with double placebo (P = 0.35). Conclusions: Cholesterol-lowering using a statin, and blood pressure-lowering using Cand+HCTZ, either alone or in combination, do not improve or adversely affect erectile function.
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    Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: Results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants
    (Oxford Academic, 2021-08-14) Bosch, Jackie; Lonn, Eva M.; Jung, Hyejung; Zhu, Jun; Liu, Lisheng; Lopez-Jaramillo, Patricio; Pais, Prem; Xavier, Denis; Diaz, Rafael; Dagenais, Gilles; Dans, Antonio; Avezum, Alvaro; Piegas, Leopoldo S.; Parkhomenko, Alexander; Keltai, Kati; Keltai, Matya; Sliwa, Karen; Held, Claus; Peters, Ronald J.G.; Lewis, Basil S.; Jansky, Petr; Yusoff, Khalid; Khunti, Kamlesh; Toff, William D.; Reid, Christopher M.; Varigos, John; Joseph, Philip; Leiter, Lawrence A.; Yusuf, Salim; The Heart Outcomes Prevention Evaluation (HOPE)-3 Investigators; Masira
    Aims. Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated. Methods and results. After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64–0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68–1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69–0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69–0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years. Conclusion. The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect
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    Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE)
    (Elsevier, 2019-09-03) Yusuf, Salim; Joseph, Philip; Rangarajan, Sumathy; Islam, Shofiqul; Mente, Andrew; Hystad, Perry; Brauer, Michael; Raman Kutty, Vellappillil; Gupta, Rajeev; Wielgosz, Andreas; AlHabib, Khalid F.; Dans, Antonio; Lopez-Jaramillo, Patricio; Avezum, Alvaro; Lanas, Fernando; Oguz, Aytekin; Kruger, Iolanthe M.; Diaz, Rafael; Yusoff, Khalid; Mony, Prem; Chifamba, Jephat; Yeates, Karen; Kelishadi, Roya; Yusufali, Afzalhussein; Khatib, Rasha; Rahman, Omar; Zatonska, Katarzyna; Iqbal, Romaina; Wei, Li; Bo, Hu; Rosengren, Annika; Kaur, Manmeet; Mohan, Viswanathan; Lear, Scott A.; Teo, Koon K.; Leong, Darryl; O'Donnell, Martin; McKee, Martin; Dagenais, Gilles; Everest
    Background Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. Methods In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. Findings Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. Interpretation Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).
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    Polypill with or without aspirin in persons without cardiovascular disease
    (The New England Journal of Medicine, 2021-01-21) Yusuf, Salim; Joseph, Philip; Dans, Antonio; Gao, Peggy; Teo, Koon; Xavier, Denis; Lopez-Jaramillo, Patricio; Yusoff, Khalid; Santoso, Anwar; Gamra, Habib; Talukder, Shamim; Christou, Courtney; Girish, Preeti; Yeates, Karen; Xavier, Freeda; Dagenais, Gilles; Rocha, Catalina; McCready, Tara; Tyrwhitt, Jessica; Bosch, Jackie; Pais, Prem; The International Polycap Study 3 Investigators; Masira
    BACKGROUND A polypill comprising statins, multiple blood-pressure–lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437. opens in new tab.)
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    Prognostic validation of a non-laboratory and a laboratory based cardiovascular disease risk score in multiple regions of the world
    (2018) Joseph, Philip; Yusuf, Salim; Lee, Shun Fu; Ibrahim, Quazi; Teo, Koon; Rangarajan, Sumathy; Gupta, Rajeev; Rosengren, Annika; Lear, Scott A.; Avezum, Alvaro; Lopez-Jaramillo, Patricio; Gulec, Sadi; Yusufali, Afzalhussein; Chifamba, Jephat; Lanas, Fernando; Kumar, Rajesh; Mohammadifard, Noushin; Mohan, Viswanathan; Mony, Prem; Kruger, Annamarie; Liu, Xu; Guo, Baoxia; Zhao, Wenqi; Yang, Youzhu; Pillai, Rajamohanan; Diaz, Rafael; Krishnapillai, Ambigga; Iqbal, Romaina; Yusuf, Rita; Szuba, Andrzej; Anand, Sonia S.
    Objective To evaluate the performance of the non-laboratory INTERHEART risk score (NL-IHRS) to predict incident cardiovascular disease (CVD) across seven major geographic regions of the world. The secondary objective was to evaluate the performance of the fasting cholesterol-based IHRS (FC-IHRS). Methods Using measures of discrimination and calibration, we tested the performance of the NL-IHRS (n=100 475) and FC-IHRS (n=107 863) for predicting incident CVD in a community-based, prospective study across seven geographic regions: South Asia, China, Southeast Asia, Middle East, Europe/North America, South America and Africa. CVD was defined as the composite of cardiovascular death, myocardial infarction, stroke, heart failure or coronary revascularisation. Results Mean age of the study population was 50.53 (SD 9.79) years and mean follow-up was 4.89 (SD 2.24) years. The NL-IHRS had moderate to good discrimination for incident CVD across geographic regions (concordance statistic (C-statistic) ranging from 0.64 to 0.74), although recalibration was necessary in all regions, which improved its performance in the overall cohort (increase in C-statistic from 0.69 to 0.72, p<0.001). Regional recalibration was also necessary for the FC-IHRS, which also improved its overall discrimination (increase in C-statistic from 0.71 to 0.74, p<0.001). In 85 078 participants with complete data for both scores, discrimination was only modestly better with the FC-IHRS compared with the NL-IHRS (0.74 vs 0.73, p<0.001). Conclusions External validations of the NL-IHRS and FC-IHRS suggest that regionally recalibrated versions of both can be useful for estimating CVD risk across a diverse range of community-based populations. CVD prediction using a non-laboratory score can provide similar accuracy to laboratory-based methods.
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    Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE)
    (Elsevier Inc., 2019-09-03) Dagenais, Gilles R.; Leong, Darryl P.; Rangarajan, Sumathy; Lanas, Fernando; Lopez-Jaramillo, Patricio; Gupta, Rajeev; Diaz, Rafael; Avezum, Alvaro; Alhabib, Khalid F.; Temizhan, Ahmet; Ismail, Noorhassim; Chifamba, Jephat; Yeates, Karen; Khatib, Rasha; Rahman, Omar; Zatonska, Katarzyna; Kazmi, Khawar; Wei, Li; Zhu, Jun; Rosengren, Annika; Vijayakumar, K.; Kaur, Manmeet; Mohan, Viswanathan; Yusufali, AfzalHussein; Kelishadi, Roya; Teo, Koon K.; Joseph, Philip; Yusuf, Salim; Elsevier; Everest
    Background To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. Methods The PURE study is a prospective, population-based cohort study of individuals aged 35–70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. Findings This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5–10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. Interpretation Among adults aged 35–70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).