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Teo K.K.,Population Health Research Institute
Journal of Hypertension | Year: 2011

Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks. Objective: Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants. Patients and methods: Individuals at high CVD risk were randomized to telmisartan (three trials, n = 51 878), irbesartan (three trials, n = 14 859), valsartan (four trials, n = 44 264), candesartan (four trials, n = 18 566), and losartan (one trial, n = 9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n = 42 403), the ARBs were compared to ACEi and in 11 trials (n = 63 313) to controls without ACEi. In addition, in seven trials (n = 47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n = 25 712). Results: Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment. Conclusion: There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Gersh B.J.,Mayo Medical School | Sliwa K.,Hatter Institute of Cardiovascular Research | Mayosi B.M.,University of Cape Town | Yusuf S.,Population Health Research Institute
European Heart Journal | Year: 2010

The epidemic of cardiovascular disease (CVD) is a global phenomenon, and the magnitude of its increase in incidence and prevalence in low-and middle-income countries (LIMIC) has potentially major implications for those high-income countries that characterize much of the developed world. Cardiovascular disease remains the leading cause of death in the world and approximately 80 of all cardiovascular-related deaths occur in LIMIC and at a younger age in comparison to high-income countries. The economic impact in regard to loss of productive years of life and the need to divert scarce resources to tertiary care is substantial. The 'epidemiologic transition' provides a useful framework for understanding changes in the patterns of disease as a result of societal and socioeconomic developments in different countries and regions of the world. A burning but as yet unanswered question is whether gains made over the last four decades in reducing cardiovascular mortality in high-income countries will be offset by changes in risk factor profiles, and in particular obesity and diabetes. Much of the population attributable risk of myocardial infarction is accountable on the basis of nine modifiable traditional risk factors, irrespective of geography. Developing societies are faced with a hostile cardiovascular environment, characterized by changes in diet, exercise, the effects of tobacco, socioeconomic stressors, and economic constraints at both the national and personal level in addition to exposure to potential novel risk factors and perhaps a genetic or programmed foetal vulnerability to CVD in later life. There are major challenges for primary and secondary prevention including lack of data, limited national resources, and the lack of prediction models in certain populations. There are two major approaches to prevention: public health/community-based strategies and clinic-based with a targeted approach to high-risk patients and combinations of these. There are concerns that in comparison with communicable diseases, cardiovascular and chronic diseases have a relatively low priority in the global health agenda and that this requires additional emphasis.The human race has had long experience and a fine tradition in surviving adversity, but we now face a task for which we have little experience, the task of surviving prosperity Alan Gregg 1890-1957, Rockefeller Foundation. © The Author 2010.

Deng W.Q.,McMaster University | Pare G.,McMaster University | Pare G.,Population Health Research Institute
Genetic Epidemiology | Year: 2011

Detection of gene-environment interactions using an exhaustive search necessarily raises the multiple hypothesis problem. While frequently used to control for experiment-wise type I error, Bonferroni correction is overly conservative and results in reduced statistical power. We have previously shown that prioritizing SNPs on the basis of heterogeneity in quantitative trait variance per genotype leads to increased power to detect genetic interactions. Our proposed method, variance prioritization (VP), selects SNPs having significant heterogeneity in variance per genotype using a pre-determined P-value threshold. We now suggest prioritizing SNPs individually such that the optimal heterogeneity of variance P-value is determined for each SNP. The large number of SNPs in genome-wide studies calls for a fast algorithm to output the optimal prioritization threshold for each SNP. In this report, we present such an algorithm, the Gene Environment Wide Interaction Search Threshold (GEWIST), and show that the use of GEWIST will increase power under a variety of interaction scenarios. Furthermore, by integrating over possible interaction effect sizes, we provide a framework to optimize prioritization in situations where interactions are a priori unknown. © 2011 Wiley Periodicals, Inc.

Sohani Z.N.,Population Health Research Institute | Samaan Z.,McMaster University
Cardiology Research and Practice | Year: 2012

Prevalence studies have noted the cooccurrence of cognitive decline and depression in persons with heart failure. Cognitive impairment is associated with significant mortality and deteriorated quality of life, likely due to impairments in memory and executive function, which impact a patient's ability to understand and comply with prescribed treatment plans. This is especially true in complex diseases such as heart failure. Evidence from literature supports the possibility of a pathophysiological relationship between cognitive impairment, depression, and heart failure. Yet, very few studies have sought to investigate this relationship. This paper reviews current literature on the association between depression and cognitive impairment in persons with heart failure and explores possible mechanisms explaining this complex triad. © 2012 Z. N. Sohani and Z. Samaan.

Benavente O.R.,University of British Columbia | Hart R.G.,Population Health Research Institute | McClure L.A.,University of Alabama at Birmingham | Szychowski J.M.,University of Alabama at Birmingham | Coffey C.S.,University of Iowa
New England Journal of Medicine | Year: 2012

BACKGROUND: Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. METHODS: We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. RESULTS: The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P = 0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone). CONCLUSIONS: Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.) Copyright © 2012 Massachusetts Medical Society. All rights reserved.

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