Search

Summary 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).

Background Cardiovascular disease risk assessment tools help identify individuals likely to benefit from preventative therapies. In this study we compared outcomes using the American College of Cardiology/American Heart Association (ACC/AHA) risk algorithm and the Framingham Risk Score (FRS) tool in the Heart Outcomes Prevention Evaluation (HOPE)-3 study. Methods We compared outcomes using the ACC/AHA algorithm and the FRS with those seen in HOPE-3, which randomized participants to 10 mg rosuvastatin or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second coprimary outcome additionally included heart failure, cardiac arrest, and revascularization. Results Relative risks using risk scores were similar to those observed in the HOPE-3. Hazards ratios for the first coprimary outcome according to risk categories of ≤ 10%, 10%-20%, and ≥ 20% using the ACC/AHA algorithm were 0.82 (95% confidence interval [CI], 0.53-1.28), 0.72 (95% CI, 0.53-0.96), and 0.72 (95% CI, 0.55-0.93), and absolute risk reduction (ARR) of 0.18%, 1.33%, and 1.85%, respectively, over a median of 5.6 years. Corresponding results using the FRS were 0.69 (95% CI, 0.36-1.35), 0.73 (95% CI, 0.52-1.01), and 0.75 (95% CI, 0.60- 0.94); and ARR of 1.32%, 0.61%, and 1.43%. Hazard ratios for the second coprimary outcome were 0.77 (95% CI, 0.51-1.14), 0.73 (95% CI, 0.56-0.95), and 0.74 (95% CI, 0.58-0.94); and ARR of 0.36%, 1.49%, and 1.85%, using the ACC/AHA algorithm and 0.76 (95% CI, 0.41-1.41), 0.70 (95% CI, 0.52-0.95), and 0.76 (95% CI, 0.62-0.94); and ARR of 1.08%, 0.83%, and 1.56% using the FRS. Conclusions The pragmatic HOPE-3 trial approach identifies in an ethnically diverse primary prevention population individuals at intermediate risk who benefit from statin therapy using simple clinical characteristics without the need for complex, currently used risk assessment tools.

Background Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. Objectives This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. Methods The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. Results The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. Conclusions The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424)

Background and aims The impact of treatment strategies on outcomes in patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) according to presenting angina has not been rigorously assessed. Methods We performed a patient-level pooled-analysis (n = 5027) of patients with stable CAD and T2DM randomized to optimal medical therapy [OMT], percutaneous coronary intervention [PCI] + OMT, or coronary artery bypass grafting [CABG] + OMT. Endpoints were death/myocardial infarction (MI)/stroke, post-randomization revascularization (both over 5 years), and angina control at 1 year. Results Increasing severity of baseline angina was associated with higher rates of death/MI/stroke (p = 0.009) and increased need for post-randomization revascularization (p = 0.001); after multivariable adjustment, only association with post-randomization revascularization remained significant. Baseline angina severity did not influence the superiority of CABG + OMT to reduce the rate of death/MI/stroke and post-randomization revascularization compared to other strategies. CABG + OMT was superior for angina control at 1 year compared to both PCI + OMT and OMT alone but only in patients with ≥ Class II severity at baseline. Comparisons between PCI + OMT and OMT were neutral except that PCI + OMT was superior to OMT for reducing the rate of post-randomization revascularization irrespective of presenting angina severity. Conclusions Presenting angina severity did not influence the superiority of CABG + OMT with respect to 5-year rates of death/MI/stroke and need for post-randomization revascularization. Presenting angina severity minimally influenced relative benefits for angina control at 1 year.

Summary Background Data are scarce on the availability and affordability of essential medicines for diabetes. Our aim was to examine the availability and affordability of metformin, sulfonylureas, and insulin across multiple regions of the world and explore the effect of these on medicine use. Methods In the Prospective Urban Rural Epidemiology (PURE) study, participants aged 35–70 years (n=156 625) were recruited from 110 803 households, in 604 communities and 22 countries; availability (presence of any dose of medication in the pharmacy on the day of audit) and medicine cost data were collected from pharmacies with the Environmental Profile of a Community's Health audit tool. Our primary analysis was to describe the availability and affordability of metformin and insulin and also commonly used and prescribed combinations of two medicines for diabetes management (two oral drugs, metformin plus a sulphonylurea [either glibenclamide (also known as glyburide) or gliclazide] and one oral drug plus insulin [metformin plus insulin]). Medicines were defined as affordable if the cost of medicines was less than 20% of capacity-to-pay (the household income minus food expenditure). Our analyses included data collected in pharmacies and data from representative samples of households. Data on availability were ascertained during the pharmacy audit, as were data on cost of medications. These cost data were used to estimate the cost of a month's supply of essential medicines for diabetes. We estimated affordability of medicines using income data from household surveys. Findings Metformin was available in 113 (100%) of 113 pharmacies from high-income countries, 112 (88·2%) of 127 pharmacies in upper-middle-income countries, 179 (86·1%) of 208 pharmacies in lower-middle-income countries, 44 (64·7%) of 68 pharmacies in low-income countries (excluding India), and 88 (100%) of 88 pharmacies in India. Insulin was available in 106 (93·8%) pharmacies in high-income countries, 51 (40·2%) pharmacies in upper-middle-income countries, 61 (29·3%) pharmacies in lower-middle-income countries, seven (10·3%) pharmacies in lower-income countries, and 67 (76·1%) of 88 pharmacies in India. We estimated 0·7% of households in high-income countries and 26·9% of households in low-income countries could not afford metformin and 2·8% of households in high-income countries and 63·0% of households in low-income countries could not afford insulin. Among the 13 569 (8·6% of PURE participants) that reported a diagnosis of diabetes, 1222 (74·0%) participants reported diabetes medicine use in high-income countries compared with 143 (29·6%) participants in low-income countries. In multilevel models, availability and affordability were significantly associated with use of diabetes medicines. Interpretation Availability and affordability of essential diabetes medicines are poor in low-income and middle-income countries. Awareness of these global differences might importantly drive change in access for patients with diabetes. Funding Full funding sources listed at the end of the paper (see Acknowledgments).

WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality.The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all50 participants) and cardiovascular disease and mortality in 255 communities (all100 participants), and used individual-level data to adjust for known confounders.95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile5·08 g/day, mean intake 5·75 g/day,5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo. RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD. CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy. ispartof: Canadian Journal of Cardiology vol:33 issue:8 pages:1027-1035 ispartof: location:England status: published

Although salt intake derived from data on urinary sodium excretion in free-living populations has been used in public policy, a population study on urinary sodium excretion has not been done in Canada. We assessed dietary sodium and potassium intake using a 24-hour urine collection in a large survey of urban and rural communities from 4 Canadian cities and determined the association of these electrolytes with blood pressure (BP).One thousand seven hundred consecutive individuals, aged 37-72 years, attending their annual follow-up visits of the ongoing Prospective and Urban Rural Epidemiology (PURE) study in Vancouver, Hamilton, Ottawa, and Quebec City, Canada, collected a 24-hour urine sample using standardized procedures.Mean sodium excretion was 3325 mg/d and mean potassium excretion was 2935 mg/d. Sodium excretion ranged from 3093 mg/d in Vancouver to 3642 mg/d in Quebec City, after adjusting for covariates. Potassium excretion ranged from 2844 mg/d in Ottawa to 3082 mg/d in Quebec City. Both electrolytes were higher in men than in women and in rural populations than in urban settings (P0.001 for all). Sodium excretion was between 3000 and 6000 mg/d in 48.3% of the participants,3000 mg/d in 46.7%, and6000 mg/d in only 5%. No significant association between sodium or potassium excretion and BP was found.Sodium consumption in these Canadians is within a range comparable to other Western countries, and intake in most individuals is6000 mg/d, with only 5% at higher levels. Within this range, sodium or potassium levels were not associated with BP.

This position statement addresses issues in revascularization for multivessel coronary artery disease (CAD) from the perspective of both cardiologists and cardiac surgeons. Recommendations are made based on evidence from clinical trials and observational studies, with an emphasis on the increasing number of individuals with significant comorbid disease burden and functional debilitation who are being referred for definitive management of their multivessel CAD in the context of routine clinical practice. These types of individuals have traditionally not been included in the many clinical trials that have been the basis for guidelines and recommendations, and the objective of the proposed medical intervention or revascularization (or both) would not necessarily be to improve prognosis but to improve quality of life. One purpose of this document is to propose practical multidisciplinary approaches to the management of these patients. Recommendations are made for revascularization in acute coronary syndromes and stable CAD, with specific considerations for individuals with left ventricular dysfunction and heart failure, chronic renal failure, and chronic obstructive pulmonary disease. We also consider the use of various risk scores, including the Society of Thoracic Surgeons score, the EuroSCORE, and the SYNTAX II score. The importance of a heart team approach is also emphasized. The complementary role of coronary bypass surgery and percutaneous coronary intervention is highlighted, along with the importance of optimal medical therapy.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up.RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

Objectives The purpose of this analysis was to assess in patients with type 2 diabetes and stable coronary artery disease (CAD) whether the risk of all-cause mortality and cardiovascular events varied according to the presence or absence of angina and angina equivalent symptoms. Background Data on the prognostic value of symptoms in these patients are limited. Methods Post-hoc analysis was performed in 2,364 patients with type 2 diabetes and documented CAD enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial to determine the occurrence of death and composite of death, myocardial infarction, and stroke during a 5-year follow-up according to cardiac symptoms at baseline. Results There were 1,434 patients with angina (A), 506 with angina equivalents (E), and 424 with neither of these (N). The cumulative death rates (total 316) were 12% in A, 14% in E, and 10% in N (p = 0.3), and cardiovascular composite rates (total 548) were 24% in A, 24% in E, and 21% in N (p = 0.5). Compared with N, the hazard ratios adjusted for confounders were not different for death in A (1.11; 99% CI: 0.81 to 1.53) and E (1.17; 99% CI: 0.81 to 1.68) or for cardiovascular events in A (1.17; 99% CI: 0.92 to 1.50) and E (1.11; 99% CI: 0.84 to 1.48). Conclusions Whatever their symptom status, patients with type 2 diabetes and stable CAD were at similar risk of cardiovascular events and death. These findings suggest that these patients may be similarly managed in terms of risk stratification and preventive therapies. (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305)

Objectives This study was designed to examine the prognostic value of systemic arterial compliance (SAC) by Doppler-echocardiography in patients with type 2 diabetes mellitus (T2D). Background Reduced SAC has been shown to predict outcomes in patients with hypertension. T2D is associated with accelerated arterial stiffening and increased cardiovascular events. We hypothesized that SAC measured by Doppler-echocardiography would independently predict mortality in patients with T2D. Methods Since 2001, SAC calculated as the ratio of stroke volume index to arterial pulse pressure by sphygmomanometer is routinely performed in our laboratory. Data from 505 consecutive patients with T2D were retrospectively analyzed. Based on a previously validated cut-off value of SAC 2 /mmHg, patients were divided into Group 1, reduced SAC, 255 patients (50%) and Group 2, preserved SAC, 250 patients (50%). The primary endpoint was overall mortality. Results Patients with reduced SAC had significantly lower 5-year survival than those with preserved SAC (66 ± 5 vs. 82 ± 5%, p = 0.02) and a 1.57-fold (95% CI: 1.04–2.43; p = 0.03) increased risk of mortality after adjusting for other risk factors. Blood pressure did not predict mortality and pseudo-normalized blood pressures related to LV dysfunction and low cardiac output were found in 75 patients (15%). Conclusion Reduced SAC is encountered frequently in T2D, is an independent predictor of mortality and allows identification of patients who, despite a normal blood pressure, are at increased risk. Future studies are necessary to further evaluate the clinical utility of this simple echocardiographic parameter and therapies are needed to alter vascular stiffness to improve clinical outcomes in these high-risk patients.

The CANadian Network and Centre for Trials INternationally (CANNeCTIN) was jointly funded by the Canadian Institutes of Health Research and the Canadian Foundation for Innovation in April 2008 to provide infrastructure for clinical studies of cardiovascular diseases and diabetes mellitus. Its functional components include a national coordinating centre at the Population Health Research Institute (PHRI) in Hamilton (Ontario), a collaborative Canadian network and an affiliated international network of hospitals and clinics. The rationales for CANNeCTIN include the global health burden of cardiovascular diseases and diabetes, the strengths of randomized controlled trials – particularly large, multicentre and international – and the track record of success of the PHRI. CANNeCTIN will provide investigators from across Canada with opportunities to become the principal investigators of national and international trials coordinated by the PHRI. CANNeCTIN will support priority pilot studies, and successful investigators will be encouraged and assisted to apply for peer review and industrial funding for full studies to be conducted within the network and coordinated by the PHRI. An extensive education program offers hands-on experience in organizing and leading large national/international clinical trials led by accomplished researchers, distance learning courses in clinical research methodology, biostatistics and study coordination, and ‘cutting-edge’ workshops. A knowledge translation program seeks opportunities arising from clinical trials and encourages research into this paradigm for understanding how best to close the gaps between knowledge and effective practice. The five-year goals are to enhance the capacity of Canadian investigators to lead major clinical studies, facilitate knowledge translation and exchange, and augment Canada’s capacity to train the next generation of leaders in cardiovascular and diabetes clinical research.

We previously observed an attenuation of exercise-induced myocardial ischemia on the ergocycle during a ramp protocol compared to the standard Bruce protocol treadmill test in patients with coronary heart disease. However, it was uncertain whether decreased ischemia on the ergocycle resulted from the warm-up effect of the more gradual ramp protocol or from the mode of exercise itself (cycling vs running). Sixteen stable patients, aged 64 +/- 5 years, with documented coronary heart disease (or =70% coronary artery stenosis and/or reversible myocardial perfusion defects) performed 3 symptom-limited exercise tests: the standard Bruce protocol treadmill test and 2 individualized ramp protocols (treadmill and ergocycle). We measured the ischemic threshold (heart rate x systolic blood pressure product at 1-mm ST-segment depression) and oxygen consumption (VO(2)). The ischemic threshold was higher during cycling (ergocycle ramp, 24,009 +/- 5,769 beats/min x mm Hg) compared to running (Bruce treadmill, 20,429 +/- 3,508 beats/min x mm Hg; and ramp treadmill, 19,451 +/- 3,392 beats/min x mm Hg; p0.001), independently of exercise intensity (VO(2)). The peak VO(2) did not significantly differ among all tests (p = 0.25) despite a greater peak rate-pressure product achieved with the ergocycle (29,378 +/- 6,291 beats/min x mm Hg) compared to either treadmill protocol (Bruce, 26,202 +/- 5,831 beats/min x mm Hg; ramp, 25,654 +/- 6,492 beats/min x mm Hg; p0.001). In conclusion, the mode of exercise (ergocycle vs treadmill), rather than the type of protocol (ramp vs Bruce), is associated with an attenuation of electrocardiographic parameters of myocardial ischemia, independently of exercise intensity (VO(2)) and myocardial demand (rate-pressure product).

Background The natural history of intermittent claudication, from its risk factors to its cardiovascular prognosis, has been reported in few prospective studies. Objective To assess incident intermittent claudication, as well as its risk factors and long-term prognosis in men. Methods A random sample of 4376 men 35 to 64 years of age from Quebec City (Quebec), who were free of cardiovascular disease (CVD), was evaluated in 1974 for CVD risk factors and followed until 1998. To assess the prognosis, the event rates between 1985 and 1998 were computed among men with incident claudication without other CVD, incident survivors of a first myocardial infarction (MI) without other CVD and men free of CVD between 1974 and 1985. Results From 1974 to 1998, 300 men developed intermittent claudication. Tobacco consumption, high systolic blood pressure and diabetes at least doubled the adjusted RR (aRR) of intermittent claudication. In 1985, there were 80 claudicants, 2868 men free of CVD and 68 survivors of a first MI. During the 13-year follow-up, a new CVD occurred in 48.8% of the claudicants, in 18.9% of men without CVD (aRR 2.08; 95% CI 1.48 to 2.90) and in 45.6% of MI survivors (aRR compared with claudicants 1.12; 95% CI 0.69 to 1.79). There was also no significant difference between claudicants and MI survivors for fatal CVD, nonfatal CVD and total mortality. Conclusions Men with intermittent claudication are at high risk for CVD that may be equivalent to men with previous MI.

Despite its widespread use, limited data on the validity of the Canadian Cardiovascular Society angina (CCSA) classification relative to other measures of functional status have been reported.To assess the validity of the CCSA classification by comparing it with the Duke Activity Status Index (DASI) and evaluate its prognostic significance with respect to long-term mortality.The study population consisted of 1407 patients who underwent cardiac catheterization between 1992 and 1996. The median follow-up period was 9.7 years (interquartile range 6.1 to 11.1 years) and the mortality status as of December 31, 2004 was available for all patients.The first three CCSA classes were inversely related to the DASI. The mean (+/- SD) scores were as follows: class I, 31.4+/-16.7; class II, 22.5+/-15.4; class III, 14.7+/-14.3; and class IV, 15.5+/-14.9 (P0.01). Increasing CCSA class was associated with increased long-term mortality, even after adjusting for baseline characteristics. Chest pain course was also an important modulator of mortality among class III and IV patients; one-year mortality rates were 8.1% among unstable patients compared with 4.8% among patients with stable or progressing course.CCSA classes I to III were inversely related to DASI scores and linearly associated with mortality. The similarity in outcomes among class III and IV patients is probably explained by the confounding effect of the stability of the patients' symptoms. The higher mortality risk among class III and IV patients with an unstable course provides impetus for a revised CCSA definition incorporating this information.

Objectives The aim of this study was to evaluate effects of the angiotensin-converting enzyme (ACE) inhibitor ramipril and the thiazolidinedione (TZD) rosiglitazone on carotid intima-media thickness (CIMT) in people with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Background People with IGT and/or IFG are at increased long-term risk for cardiovascular disease. Effects of ACE inhibitors and of TZDs on vascular disease in this population are unknown. Methods One thousand four hundred twenty-five people with IGT and/or IFG but without cardiovascular disease or diabetes were randomized to ramipril 15 mg/day or its placebo and to rosiglitazone 8 mg/day or its placebo with a 2 × 2 factorial design. The primary study outcome was the annualized change of the aggregate maximum CIMT, computed as the average of the maximum CIMTs across 12 carotid arterial segments. The secondary study outcome was the annualized change of the mean far wall left and right common CIMT. Median follow-up was 3 years and carotid ultrasound examinations were obtained at baseline and yearly thereafter. Results There were no differences in the primary and secondary outcomes between the ramipril and placebo groups. Compared with placebo, rosiglitazone reduced the primary CIMT outcome, but the difference was not statistically significant (difference = 0.0027 ± 0.0015 mm/year; p = 0.08) and significantly reduced the secondary CIMT outcome (difference = 0.0043 ± 0.0017 mm/year; p = 0.01). Conclusions In people with IGT and/or IFG without cardiovascular disease and diabetes, treatment with ramipril had a neutral effect on CIMT, whereas rosiglitazone modestly reduced CIMT progression. (The Study of Atherosclerosis With Ramipril and Rosiglitazone; NCT00140647 ).

Objectives This study was designed to prospectively determine, in patients with an acute coronary syndrome, whether the inflammatory marker, C-reactive protein (CRP), measured at hospital admission, discharge, and 1 month later has incremental value to predict outcomes at 1 year. Background The clinical utility of CRP measurements in patients with acute coronary syndromes remains uncertain. Limitations of previous studies have been retrospective design and incomplete adjustment for readily available clinical prognosticators. Methods The CRP marker was measured at admission, hospital discharge, and 1 month later in consecutive patients hospitalized for acute coronary syndromes in 8 tertiary and secondary hospitals. The primary outcome was a composite of death, nonfatal myocardial infarction (MI), and unstable angina (UA) with electrocardiogram (ECG) changes at 1 year. Results A total of 1,210 patients, age 62 ± 12 years, 64% with acute myocardial infarction (MI) and 36% with unstable angina (UA), were recruited. At 1 year, the primary outcome occurred in 142 patients (11.7%) and included 58 deaths (4.8%), 79 nonfatal MIs (6.5%), and 26 UA episodes with ECG changes (2.1%). The unadjusted odds ratios (ORs) (95% confidence intervals) of CRP values at admission, hospital discharge, and 1 month later for the occurrence of the primary outcome were 1.20 (1.06 to 1.36), 0.98 (0.85 to 1.14), and 1.23 (1.00 to 1.50), respectively. After multivariate adjustment, ORs were 1.04 (0.91 to 1.20), 0.90 (0.77 to 1.06), and 1.12 (0.93 to 1.34), respectively. The individual components of the primary outcome were also not independently associated with any of the 3 CRP measurements. Conclusions The modest predictive ability of CRP following admission for an acute coronary syndrome disappeared after adjusting for common clinical variables. This large prospective study does not support the incremental value of measuring CRP in this clinical setting.

We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43–1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07–2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97–2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors ( p =0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals.

Increased body mass index (BMI) and abdominal adiposity increase the risk of cardiovascular disease (CVD) in persons free of these diseases, but their independent prognostic impact in persons with CVD has not been well defined.BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were measured in 6620 men and 2182 women with a mean age of 66 and stable CVD without congestive heart failure (CHF) participating in the Heart Outcomes Prevention Evaluation (HOPE) study. The main outcomes were CVD death, myocardial infarction, stroke, hospitalization for CHF, and all-cause mortality.During the 4.5-year follow-up, 658 had a CVD death, 1018 a myocardial infarction, 364 a stroke, 297 a CHF event, and 1034 died. When compared with the first tertile, the third tertile of BMI increased the adjusted relative risk (RR) of myocardial infarction by 20% (P.02). Patients in the third tertile of WC had an increased adjusted RR of 23% for myocardial infarction (P.01), 38% for heart failure (P.03), and 17% for total mortality (P.05). For WHR, there was an increased adjusted RR of 24% for CVD death (P.03), 20% for myocardial infarction (P.01), and 32% for total mortality (P.001).Obesity, particularly abdominal adiposity, worsens the prognosis of patients with CVD; weight reduction program should be integrated in the active management of these patients.

Background Hypertension is a well-established risk factor for myocardial infarction (MI), but its prognostic importance in survivors of an acute MI is less clear. Methods We used Cox proportional hazards models to examine the risk of any major cardiovascular event (cardiovascular death, heart failure, recurrent MI, or stroke)—combined or individual components—and all-cause death and evaluate the efficacy of captopril in 906 patients with hypertension and 1325 patients without hypertension in the Survival and Ventricular Enlargement (SAVE) clinical trial. All patients had survived an acute MI with resultant left ventricular (LV) systolic dysfunction, but without overt heart failure, and were randomized within 3 to 16 days after the index MI to receive either captopril or placebo. The mean (± SD) follow-up period was 42 ± 10 months. Results After adjustment for known risk factors, medication use at enrollment, and baseline systolic blood pressure, patients with hypertension had a significant increase in the risk of experiencing a combined cardiovascular event (47.7% vs 31.3%; hazard ratio [HR], 1.49; 95% CI, 1.28–1.74), cardiovascular death (23.4% vs 15.9%; HR, 1.40; 95% CI, 1.12–1.74), heart failure (27.7% vs 15.5%; HR, 1.64; 95% CI, 1.34–2.02), and all-cause death (27.4 vs 19.3%; HR, 1.25; 95% CI, 1.02–1.53), and a similar but statistically non-significant increase in the risk of non-fatal or fatal recurrent MI (17.4% vs 10.9%; HR, 1.27; 95% CI, 0.98–1.65), and non-fatal or fatal stroke (5.0% vs 3.6%; HR, 1.31; 95% CI, 0.81–2.09). Captopril resulted in similar benefits for both patients with and patients without hypertension. The number of combined cardiovascular events prevented for every 100 patients treated with captopril was 7.0 (95% CI, 0.5–13.5) in patients with hypertension and 7.5 (95% CI, 2.6–12.5) in patients without hypertension. Conclusions In survivors of an acute MI with LV systolic dysfunction, antecedent hypertension was associated with a greater risk of subsequent adverse cardiovascular events, not directly explained by elevated blood pressure levels. Captopril use was beneficial in both patients with and patients without hypertenson.

This purpose of this study was to investigate how plasma C-reactive protein (CRP), a nonspecific acute-phase reactant, modulates the risk of coronary heart disease (CHD) associated with the small, dense, low-density lipoprotein (LDL) phenotype. LDL particle size and plasma CRP were measured in the Quebec Cardiovascular Study cohort of 2,025 men free of CHD at baseline, among whom 103 had a first CHD event during a 5-year follow-up period. Plasma CRP levels were measured using the Behring Latex-Enhanced (highly sensitive) CRP assay. LDL particle size phenotype was characterized using 2% to 16% polyacrylamide gradient gel electrophoresis. There were weak but significant associations between plasma CRP levels and features of LDL size, such as the proportion of LDL with a diameter

Background: Primary as well as secondary prevention trials have shown the relevance of lowering LDL-cholesterol to reduce coronary heart disease (CHD) risk. However, although the association between LDL-cholesterol and CHD is well recognized, there is a considerable overlap in the distribution of plasma LDL-cholesterol levels between CHD patients and healthy subjects. The objective of the present review article is to use data from the Quebec cardiovascular study to demonstrate that in men, a low HDL-cholesterol may be even more of a risk factor and a target for therapy than a high LDL-cholesterol. Methods and results: Results of the Quebec cardiovascular study, a prospective study of 2103 middle-aged men followed for a period of 5 years, have confirmed results of previous studies in showing that plasma HDL-cholesterol concentration was an independent predictor of a first ischemic heart disease (IHD) event which included typical effort angina, coronary insufficiency, nonfatal myocardial infarction and coronary death. In addition, a reduced plasma HDL-cholesterol concentration was found to have a greater impact than raised LDL-cholesterol on the atherogenic index (total cholesterol/HDL-cholesterol ratio), this ratio being the best variable of the traditional lipid profile for the prediction of IHD events in the Quebec cardiovascular study. However, a low HDL-cholesterol concentration is not often observed as an isolated disorder but also includes hypertriglyceridemia, elevated apo B concentration, and an increased proportion of small, dense LDL particles. These abnormalities are features of an insulin resistant-hyperinsulinemic state resulting from abdominal obesity. Conclusions: It is therefore recommended that we need to go beyond LDL-cholesterol measurement lowering therapy for the optimal management of CHD risk. Raising plasma HDL-cholesterol through weight loss and a healthy diet, by an increased physical activity and, if required, by proper pharmacotherapy is therefore a legitimate therapeutic target for the optimal prevention of CHD in a large proportion of high risk patients.

A sample of 2,103 men aged 47 to 76 years from the Québec Cardiovascular Study cohort was examined to quantify the influence of plasma triglyceride (TG) levels on the relationship between plasma lipoprotein cholesterol and either apolipoprotein A-I (apo A-I) or apo B concentrations. Regression analyses between high-density lipoprotein cholesterol (HDL-C) and apo A-I through TG tertiles showed highly significant correlations (.62or = ror = .75, P.0001) in all TG tertiles between these 2 variables. The associations for plasma apo B versus low-density lipoprotein cholesterol (LDL-C) and non-HDL-C levels were also studied on the basis of TG concentrations, and correlation coefficients between either LDL-C or non-HDL-C and apo B were essentially similar among TG tertiles (.78or = ror = .85 and .83or = ror = .86 for LDL-C and non-HDL-C, respectively, P.0001). Regression analyses also showed that lower HDL-C levels were found for any given apo A-I concentration among men in the 2 upper TG tertiles, whereas lower LDL-C concentrations were observed at any given apo B level among subjects in the upper TG tertile. We further investigated whether there were synergistic alterations in the HDL-C/apo A-I and LDL-C/apo B ratios as a function of increasing plasma TG. A significant association was noted between these 2 ratios (r = .37; P.0001). Mean HDL-C/apo A-I and LDL-C/apo B ratios were then calculated across quintiles of plasma TG concentrations. Increased TG concentrations were first associated with a reduced HDL-C/apo A-I ratio, followed by a decreased LDL-C/apo B ratio. These results suggest that a relatively modest increase in TG may rapidly alter the relative cholesterol content of HDL particles. Finally, the cholesterol content of the non-HDL fraction appears to be influenced less by TG levels than HDL-C and LDL-C fractions. Thus, the plasma apo B-containing lipoprotein cholesterol level may provide a better index of number of atherogenic particles than the LDL-C concentration, particularly in the presence of hypertriglyceridemia (HTG).

Summary There is no doubt that visceral obesity increases thesusceptibility to IHD, emphasizing the need to consider this condition in the risk management of IHD. The use of CT or MRI as clinical tools to assess visceral adipose tissue accumulation does not appear to be justified, however, mostly because of the costs of the procedures and the limited availability of the necessary apparatus. The waist:hip ratio has been used extensively as an indicator of body fat distribution. However, it has been shown that the waist:hip ratio is less accurate than the waist circumference alone or the sagittal diameter in predicting - visceral adipose tissue accumulation, particularly when monitoring changes in visceral adipose tissue mass over time. Also, the prediction of visceral adipose tissue levels by the waist circumference alone, as opposed to the waist:hip ratio, does not appear to be affected by gender or by the degree of obesity. For these reasons we have proposed that the waist circumference should be systematically measured in managing the risk of IHD. It is a simple and inexpensive measurement to perform, while providing potentially critical information on the risk profile of both men and women. We believe that identification of viscerally obese patients, a high-risk population for IHD, should be considered as a critical step in the risk management of IHD.

Objectives. This study was undertaken to determine whether lipoprotein(a) [Lp(a)] is an independent risk factor for ischemic heart disease (IHD) and to establish the relation of Lp(a) to the other lipid fractions. Background. Several, but not all, studies have shown that elevated Lp(a) concentrations may be associated with IHD; very few have been prospective. Methods. A 5-year prospective follow-up study was conducted in 2,156 French Canadian men 47 to 76 years old, without clinical evidence of IHD. Lipid measurements obtained at baseline included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apoprotein B and Lp(a). During the follow-up period, there were 116 first IHD events (myocardial infarction, angina, death). Adjusted proportional hazards models were used to estimate the relative risk for the different variables. The cohort was also classified according to Lp(a) levels and other lipid risk factor tertiles to evaluate the relation of elevated Lp(a) levels to these risk factors. A cutoff value of 30 mg/dl was used for Lp(a). Risk ratios were calculated using the group with low Lp(a) levels and the first tertile of lipid measures as a reference. Results. Lp(a) was not an independent risk factor for IHD but seemed to increase the deleterious effects of mildly elevated LDL cholesterol and elevated total cholesterol and apoprotein B levels and seemed to counteract the beneficial effects associated with elevated HDL cholesterol levels. Conclusions. In this cohort, Lp(a) was not an independent risk factor for IHD but appeared to increase the risk associated with other lipid risk factors.

Onset of acute myocardial infarction (AMI) follows a diurnal periodicity, with a peak incidence between 6:00 a.m. and noon. Beta blockers and aspirin decrease the rate of AMI and blunt the peak incidence, but such an effect has not been evaluated for angiotensin-converting enzyme inhibitors. The effect of ramipril on onset of symptomatic AMI was evaluated in 4-hour periods over a 24-hour cycle in men and women who wereor =55 years of age, had cardiovascular disease or diabetes mellitus withor =1 other risk factor, and participated in the Heart Outcomes Prevention Evaluation (HOPE) trial. During the 4.5-year follow-up, AMI was documented in 383 of 4,596 participants allocated to ramipril and in 491 of 4,598 participants allocated to placebo (8.3% vs 10.7%, p0.001). Ramipril decreased rates of AMI at each period and attenuated, but did not blunt, the peak incidence. In conclusion, inhibiting angiotensin-converting enzyme decreased AMI over a 24-hour period, but this enzyme does not seem to play a major role in the circadian periodicity of this acute event.

Objectives. We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings.Background. In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate–pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear.Methods. We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, ≥70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized.Results. Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = −0.22, 95% CI −0.44 to −0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = −0.25, 95% CI −0.47 to −0.01, p < 0.05) and the redistribution gradient (r = −0.33, 95% CI −0.53 to −0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent.Conclusions. In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.(J Am Coll Cardiol 1997;29:1497–504)

The relative importance of reduced plasma high density lipoprotein-cholesterol (HDL-C) levels and elevated plasma triglyceride (TG) concentrations as risk factors for ischemic heart disease (IHD) was examined in a sample of 2177 men from the Québec City suburbs. The sample included 202 men with known IHD. The relationship between HDL-C and TG levels, although significant (r = -0.49, P0.0001), was not linear, as most of the variation in HDL-C levels was observed within TG levels below 2.5 mmol/l. Reduced HDL-C (0.9 mmol/l) was a prevalent condition in men with IHD (50%) compared to those without IHD (30%). On the other hand 26% and 20% of men with and without IHD, respectively, had elevated TG levels (TG2.3 mmol/l). A 2-fold increase in prevalence odds ratio (OR) was observed in men with TG levels2.3 mmol/l (95% confidence intervals (CI) [1.2;3.3]). No residual association between elevated TG levels and IHD was found, however, after adjustment for HDL-C concentrations (OR 1.2, 95% CI 0.7;2.1). On the other hand, HDL-C remained a significant predictor of IHD after adjustment for other risk factors (OR 0.3, 95%, CI 0.2;0.6). Men with reduced HDL-C levels were also characterized by a cluster of risk factors such as obesity, diabetes mellitus and hypertension, which may contribute to increase the risk of IHD. Finally, the independent interpretation of cholesterol, TG or LDL-C levels may lead to an inadequate prediction of risk, as a large number of IHD patients showed a cluster of risk factors which included low HDL-C concentrations.

In 1985, plasma cholesterol, triglyceride, high-density lipoprotein cholesterol, and plasma apoprotein (apo) B levels were measured in 2,103 men (aged 45 to 76 years) without ischemic heart disease from the Quebec city suburbs. Occurrence of a first ischemic event (i.e., angina pectoris, acute myocardial infarction, or coronary-related death) was recorded in 114 men between 1985 and 1990. Men with and without ischemic heart disease were classified as normal or in various dyslipidemic groups according to an established algorithm. Of the 1,989 men who remained free of ischemic events, 50% had a normal lipid profile compared with 32% in men with ischemic heart disease. Although the prevalence of type IIb and IV dyslipidemias was similar in men with and without ischemic heart disease, type IIa (16% vs 10%), hyperapo B-hypertriglyceridemia (12% vs 6%), hyperapo B-normotriglyceridemia (11% vs 7%), and hypoalphalipoproteinemia (18% vs 13%) were more prevalent in men with than without ischemic heart disease. Adjusted odds ratios (ORs) were not increased in type IIb and IV phenotypes, whereas men with type IIa (OR 2.8), with the 2 hyperapo B phenotypes (hyperapo B-normotriglyceridemia, OR 2.7; hyperapo B-hypertriglyceridemia, OR 3.1) or with isolated hypoalphalipoproteinemia (OR 2.2), were at higher risk. The results of this prospective study confirm the importance of both elevated plasma cholesterol and decreased high-density lipoprotein cholesterol levels as risk factors for ischemic heart disease. They also emphasize the high prevalence of an elevated apo B dyslipidemic state in ischemic heart disease.

This study was undertaken to evaluate the distribution and the relation of lipoprotein(a) (Lp[a]) concentration with intermittent claudication in a cohort of men aged 35 to 64 years, randomly selected in 1974 and followed until 1990. In 1985, blood samples for a complete fasting lipid profile and Lp(a) were obtained in 2,424 men representing 62% or the living cohort. The diagnosis of intermittent claudication was made by trained nurses using a standardized questionnaire and confirmed by a cardiologist. Lp(a) distribution did not change with age and was similar to that of other Caucasian populations. Because Lp(a) concentration did not vary with age, its relation to the incidence of intermittent claudication was assessed for the years 1974 to 1990. The incidence of intermittent claudication was 42 of 10,000 person-years. The 113 men with intermittent claudication, in contrast to men without this symptomatology, were older at entry (49 ± 7 vs 45 ± 7 years), and had higher systolic pressure (144 ± 20 vs 136 ±16 mm Hg) and Lp(a) levels (46 ± 45 vs 33 ± 35 mg/dl) (all p

In 1990, the Canadian Cardiovascular Society (CCS) approved a strategic plan intended to better fulfill its mission ‘to foster optimal cardiovascular health’. The 13 objectives of this first plan focused mainly on education, training, research, care and ethics. This report highlights the realization of some of these objectives during the 1990s.

In an ongoing ischemic heart disease (IHD) risk factor study, plasma lipid, Lp(a) and fibrinogen measurements were performed in 2125 men aged 4575 years in 1985. The subjects were followed until September 1st 1990. During that period, 116 first IHD events were documented (myocardial infarction, angina and IHD death). Subjects with IHD were older (59 ± 8 vs 56 ± 7 years; p l 0.001), had higher systolic pressure (137 ± 17 vs 130 ± 17 mmHg; p l 0.001). a higher frequency of smoking ≥ 20 cig/d (32 vs 23%; p = 0.027) and a higher prevalence of diabetes (16 vs 4%; p l 0.001). Total cholesterol (235 ± 41 vs 221 ± 39 mg/dL; p l 0.001), LDL-cholesterol (162 ± 37 vs 149 ± 35 mg/dL; p l 0.001), Lp(a) (41.0 ± 45.9 vs 32.7 ± 34.9 mg/dL; p = 0.014) and fibrinogen (3.89 ± 0.81 vs 3.55 ± 0.75 g/L; p l 0.001) levels were higher in IHD while HDL-cholesterol was lower (37 ± 9 vs 40 ± 10 mg/dL; p = 0.005). Adjusted risk ratios were significantly increased in the third fibrinogen tertile (2.4 ± 0.3; P l 0.001) but not in the second fibrinogen nor in any Lp(a) tertile. In order to further ascertain the role of fibrinogen and Lp(a), subjects were assigned to one of four groups according to fibrinogen and Lp(a) levels. The cutoff point for fibrinogen was the median of the distribution (3.52 g/l) and 25 mg/dl for Lp(a). Group 1: fibrinogen l3.52 g/l and Lp(a) l25 mg/dL; Group 2: fibrinogen l3.52 g/l and Lp(a) ≥25 mg/dL; Group 3: fibrinogen ≥3.52 g/l and Lp(a) l25 mg/dL; Group 4: fibrinogen ≥3.52 g/l and Lp(a) ≥25 mg/dL. Risk ratios were estimated for each group using Group 1 as a reference and were only significantly elevated for Group 4 (2.6 ± 0.3; p l 0.0011. The findings of this prospective study indicate that high fibrinogen levels are associated with a greater risk of IHD and that risk is associated with high Lp(a) levels.

Improved prosthetic aortic valves have reduced the incidence of complications to a point where it can be hypothesized that functional class I subjects after aortic valve replacement (AVR) should adapt to a vigorous training program without a significant increase of hemolytic activity or clinical signs of prosthesis malfunction. To test this hypothesis, 10 men (mean age 52 years) who had undergone AVR (7 Björk-Shiley and 3 Lillehei-Kaster) were submitted to an 8-week training program on ergometer, 3 times/week, from 60 to 80% of individual maximal heart rate. Ten other men who had undergone AVR but did not participate in the training program were control subjects. The exercise program produced significant improvements in posttraining maximum tolerated ergometer work load (210 kpm, p less than 0.001), in maximum total body oxygen consumption (5 ml/kg X min-1, p less than or equal to 0.01) and in double product at submaximal work load (-5,126, p less than or equal to 0.01). After training, hemoglobin decreased by about 1 g% (p less than or equal to 0.05) and hematocrit, reticulocyte counts and haptoglobin did not change significantly. Serum LDH and serum AST did not increase. Pre- and post-training echocardiograms did not show detectable alterations. Thus, patients with AVR who are in functional class I can adapt to a physical exercise program without significant adverse effects.