Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis

VA Boston Healthcare System, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02132, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 09/2010; 304(12):1350-7. DOI: 10.1001/jama.2010.1322
Source: PubMed


Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear.
To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors.
Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009.
Rates of cardiovascular death, myocardial infarction, and stroke.
A total of 45,227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all comparisons). In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly higher risk of the primary end point.
Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.

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Available from: Elizabeth Mahoney, Oct 04, 2015
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    • "Chronic conditions such as atherothrombotic disease remain one of the most significant health problems in terms of morbidity and mortality in the world, and also impose a large burden on health care budgets [1] [2] [3]. Despite improvements in quality of life due to interventions, patients with atherothrombotic disease continue to be undertreated and do not receive secondary preventive medications as per recommended guidelines [2] [4]. Furthermore, the prevalence of disease and excess costs of care are expected to increase even further due to rapidly ageing population and high prevalence of abdominal obesity which in turn will pose a substantial burden [5] among this group of population. "
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    ABSTRACT: Atherothrombotic diseases are the leading health problems in the world, both in terms of morbidity and mortality. This study aimed to identify and quantify the predictors of medication, hospital and outpatient service use among patients with or at high risk of atherothrombotic disease. Two-year follow-up data were analyzed for 2873 Australian participants of the Reduction of Atherothrombosis for Continued Health (REACH) registry. The analysis was performed using generalized linear models with Poisson and Gamma distributions and log link function. Participants with hypercholesterolemia, diabetes, hypertension, atrial fibrillation (AF), and history of coronary artery disease (CAD) used more medications (p<0.0001). The presence of diabetes predicted higher number of outpatient visits (RR=1.09, 95% CI: 1.07-1.11), as did AF (RR=1.10, 95% CI: 1.08-1.12). The presence of peripheral artery disease (PAD) regardless of ankle brachial index (ABI) status (abnormal or normal) increased the use of outpatient visits (RR=1.24, 95% CI: 1.20-1.29 and RR=1.12, 95% CI: 1.08-1.15), compared to those without PAD. Similarly, the presence of PAD regardless of ABI status increased the risk of vascular interventions, including coronary angioplasty, carotid surgery, amputation affecting lower-limb and peripheral bypass graft (RR=3.64, 95% CI: 2.01-6.60) (RR=2.8, 95% CI: 1.6-4.92) compared to patients without PAD. The presence of PAD regardless of ABI status predicts a higher number of outpatient visits, non-fatal cardiovascular endpoints and vascular-interventions, while diabetes predicts higher pharmaceutical use and outpatient visits. AF predicts the higher number of outpatient visits and non-fatal cardiovascular events.
    International journal of cardiology 04/2014; 175(1). DOI:10.1016/j.ijcard.2014.04.230 · 4.04 Impact Factor
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    • "In the REACH Registry, all major CV event rates increased with the number of vascular disease, ranging from 12.6% for patients with single, 21.1% for patients with double, and 26.3% for patients with triple vascular disease during 1-year follow up [6]. Furthermore, among patients with atherothrombosis, those with a prior history of myocardial infarction or stroke at baseline had the higher rate of subsequent ischemic events (18.3%) than those with a stable CAD, CVD, or PAD at baseline (12.2%) during 4-year follow up [7]. In the present study, in Taiwanese patients with atherothrombotic disease, we consistently found the subsequent adverse CV events including ACS, all stroke, vascular procedures, and in hospital mortality were progressively increased as the increase of atherothrombotic disease score. "
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    ABSTRACT: Atherothrombotic diseases including cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial disease (PAD), contribute to the major causes of death in the world. Although several studies showed the association between polyvascular disease and poor cardiovascular (CV) outcomes in Asian population, there was no large-scale study to validate this relationship in this population. This retrospective cohort study included patients with a diagnosis of CVD, CAD, or PAD from the database contained in the Taiwan National Health Insurance Bureau during 2001-2004. A total of 19954 patients were enrolled in this study. The atherothrombotic disease score was defined according to the number of atherothrombotic disease. The study endpoints included acute coronary syndrome (ACS), all strokes, vascular procedures, in hospital mortality, and so on. The event rate of ischemic stroke (18.2%) was higher than that of acute myocardial infarction (5.7%) in our patients (P = 0.0006). In the multivariate Cox regression analyses, the adjusted hazard ratios (HRs) of each increment of atherothrombotic disease score in predicting ACS, all strokes, vascular procedures, and in hospital mortality were 1.41, 1.66, 1.30, and 1.14, respectively (P≦0.0169). This large population-based longitudinal study in patients with atherothrombotic disease demonstrated the risk of subsequent ischemic stroke was higher than that of subsequent AMI. In addition, the subsequent adverse CV events including ACS, all stroke, vascular procedures, and in hospital mortality were progressively increased as the increase of atherothrombotic disease score.
    PLoS ONE 03/2014; 9(3):e92577. DOI:10.1371/journal.pone.0092577 · 3.23 Impact Factor
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    • "We demonstrate how real-world clinical data (as distinct from research data7,8) contribute important prognostic information in unselected patients. Unlike previous reports of prognostic models,1,7–9 we focus on potential clinical usefulness and demonstrate how each predictor usefully improves predictions beyond more simple models. Importantly, we confirm that the models have good calibration and discrimination when applied to an external study. "
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    ABSTRACT: The population with stable coronary artery disease (SCAD) is growing but validated models to guide their clinical management are lacking. We developed and validated prognostic models for all-cause mortality and non-fatal myocardial infarction (MI) or coronary death in SCAD. Models were developed in a linked electronic health records cohort of 102 023 SCAD patients from the CALIBER programme, with mean follow-up of 4.4 (SD 2.8) years during which 20 817 deaths and 8856 coronary outcomes were observed. The Kaplan-Meier 5-year risk was 20.6% (95% CI, 20.3, 20.9) for mortality and 9.7% (95% CI, 9.4, 9.9) for non-fatal MI or coronary death. The predictors in the models were age, sex, CAD diagnosis, deprivation, smoking, hypertension, diabetes, lipids, heart failure, peripheral arterial disease, atrial fibrillation, stroke, chronic kidney disease, chronic pulmonary disease, liver disease, cancer, depression, anxiety, heart rate, creatinine, white cell count, and haemoglobin. The models had good calibration and discrimination in internal (external) validation with C-index 0.811 (0.735) for all-cause mortality and 0.778 (0.718) for non-fatal MI or coronary death. Using these models to identify patients at high risk (defined by guidelines as 3% annual mortality) and support a management decision associated with hazard ratio 0.8 could save an additional 13-16 life years or 15-18 coronary event-free years per 1000 patients screened, compared with models with just age, sex, and deprivation. These validated prognostic models could be used in clinical practice to support risk stratification as recommended in clinical guidelines.
    European Heart Journal 12/2013; 35(13). DOI:10.1093/eurheartj/eht533 · 15.20 Impact Factor
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