Supplementary Material for: Is It Time to Update How Suspected Angina Is Evaluated prior to the Use of Specialized Tests? Implications Based on a Systematic Review

<b><i>Objectives:</i></b> Appropriate use of specialized tests to assess chest pain is based classically on minimal information such as age, gender and the patient's description of pain. This approach has not been reevaluated in decades. We examined the relationship between history, examination and routine laboratory tests to identify factors warranting prospective validation as predictors of underlying coronary artery disease (CAD). <b><i>Methods:</i></b> Studies linking obstructive CAD (≥50% diameter stenosis of at least one vessel by invasive angiography or cardiac computed tomographic angiography) and elements of history, examination and laboratory tests were identified. <b><i>Results:</i></b> Forty-one prospectively identified papers were analyzed. Advanced age, gender and chest pain descriptors were extremely important, although the last was less so in women, in whom the presence of risk factors may be more important. Physical examination and chest X-ray were largely noncontributory. Laboratory tests were of variable utility other than to identify risk factors not already known from the history. However, biomarkers such as troponin, brain natriuretic factor and inflammatory markers were promising. The electrocardiogram was mainly important for the identification of ST-T abnormalities. <b><i>Conclusions:</i></b> This review identifies the most promising factors warranting prospective validation for improving the pretest probability estimation of CAD, so appropriate use criteria for the utilization of specialized diagnostic tests can be updated and improved

Can combining different risk interventions into a single formulation contribute to improved cardiovascular disease risk reduction? Rationale and design for an international, open-label program to assess the effectiveness of a single pill (amlodipine/atorvastatin) to attain recommended target levels for blood pressure and lipids (The JEWEL Program).

BACKGROUND: In order to prevent cardiovascular events, it is essential to effectively manage overall risk of cardiovascular disease. However, despite guideline recommendations to this effect, current management of the major, modifiable cardiovascular risk factors such as hypertension and dyslipidemia is disconnected and patient adherence to therapy is poor. This is particularly important for patients with multiple cardiovascular risk factors, who are often prescribed multiple medications. The JEWEL study program will investigate the use of single-pill amlodipine/atorvastatin as a strategy to improve management of these patients. METHODS: The JEWEL program consists of two 16-week, international, open-label, multicenter, titration-to-goal studies in patients with hypertension and dyslipidemia. The 2 studies differ based on country of enrollment and certain tertiary endpoints, but the overall designs are very similar. Patients have been enrolled from 255 centers across Canada and 13 European countries. The study is designed to assess the efficacy, safety, and utility of amlodipine/atorvastatin single-pill therapy in a real-world setting. Patients will be initiated at a dose of amlodipine 5 mg/atorvastatin 10 mg, unless previously treated, and will be uptitrated as necessary. The primary efficacy parameter is the percentage of patients, at different levels of cardiovascular risk, achieving country-specific guideline-recommended target levels for blood pressure and lipids. A secondary analysis of efficacy measured attainment of the same single goal for blood pressure across all study participants (JEWEL I and II) and the same single goal for LDL-C across all study participants (JEWEL I and II). The program will utilize a newly developed questionnaire to gain better understanding of participants' beliefs and behaviors towards medical treatment of their multiple risk factors. Approximately 2850 patients will be enrolled in the program, which is due to be completed in August 2005. CONCLUSION: The JEWEL program will assess the effectiveness of a single pill (amlodipine/atorvastatin) in targeting the two principal risk factors for cardiovascular disease simultaneously to achieve nationally applicable treatment targets in a routine clinical practice setting

Cardiovascular risk among stable individuals suspected of having coronary artery disease with no modifiable risk factors: results from an international multicenter study of 5262 patients

Purpose: To assess the prevalence, extent, severity, and risk of coronary artery disease (CAD) in patients suspected of having CAD but with no medically modifiable risk factors. Materials and Methods: Institutional review board approval or waiver of consent was obtained at each center. This study was HIPAA compliant. From an international multicenter cohort study of 27 125 subjects undergoing coronary computed tomographic (CT) angiography from 12 centers, 5262 patients without known CAD and without modifiable risk factors were identified. CAD severity was defined as none (0%), mild (1%-49%), or obstructive (≥50%) on a per-patient, per-vessel, and per-segment basis. CAD presence, extent, and severity were related to incidence of major adverse cardiovascular event (MACE) by using Cox proportional hazards models. Results: At a mean follow-up of 2.3 years ± 1.2 (standard deviation), MACE occurred in 106 patients. CAD was common for nonobstructive (n = 1452, 27%) and obstructive (n = 629, 12%) CAD. In risk-adjusted analysis, per-patient obstructive CAD (hazard ratio [HR], 6.64; 95% confidence interval [CI]: 3.68, 12.00; P ≤ .001) was related to MACE. MACE was associated with a dose-response relationship to the number of vessels exhibiting obstructive CAD, increasing risk for obstructive one-vessel (HR, 6.11; 95% CI: 3.22, 11.6; P ≤ .001), two-vessel (HR, 5.86; 95% CI: 2.75, 12.5; P ≤ .0001), or three-vessel or left main (HR, 11.69; 95% CI: 5.38, 25.4; P ≤ .001) CAD. The increased hazard for MACE of obstructive disease holds true for symptomatic (HR, 11.9; 95% CI: 4.81, 29.6; P ≤ .001) and asymptomatic (HR, 6.3; 95% CI: 2.4, 16.7; P ≤ .001) patients. No CAD at coronary CT angiography was associated with a low annualized MACE rate: 0.31% versus 2.06% with obstructive disease. Conclusion: Among individuals suspected of having CAD but without modifiable risk factors, CAD is common, with significantly increased hazards for MACE and mortality. © RSNA, 2013