Intermediate Framingham Risk Score Research Articles

How Accurate Are 3 Risk Prediction Models in US Women?

Cardiovascular disease (CVD) is the leading cause of death for US women, and nearly two thirds who died suddenly of CVD had no previous symptoms.1 Therefore, it is of great importance to identify “at-risk” women early, so that effective primary prevention strategies can be instituted. A universal recommendation of prevention guidelines is that all asymptomatic women should undergo a global risk assessment.2 Article see p 1748 The Adult Treatment Panel III (ATP-III) of the National Cholesterol Education Program set thresholds for lipid treatment based on one's predicted 10-year risk for a hard coronary heart disease (CHD) event (myocardial infarction or CHD death) using a modified Framingham risk score (FRS).3 There are limitations, however, with use of the ATP-III model for CVD prediction in women. The ATP-III version predicts “hard” CHD events but not angina or revascularizations, even if such revascularizations are performed to manage an acute coronary syndrome. Yet women are more likely to experience “soft” CHD events or strokes than men. Moreover, a single laboratory measurement does not reflect lipid values over a woman's lifetime. The FRS does not take into account family history of premature CHD, a well-established independent risk factor for CHD events.4 Also, because stroke accounts for a higher proportion of CVD events than CHD in women before age 75 years,1 we believe that total CVD risk should be the outcome for prediction and preventive strategies. Indeed, that is the conclusion of the 2011 American Heart Association CVD prevention guidelines for women.5 Furthermore, the FRS only predicts 10-year risk, whereas for women, the issue is most often “lifetime” risk. The Third National Health and Nutrition Examination Survey found that among women without a history of CHD or diabetes, 92% of those aged 60 to 69 years and >98% aged <59 …

Evaluation of the appropriateness criteria for coronary computed tomography angiography in an academic medical center in a developing country: Comparison of the 2006 and 2010 criteria

BackgroundThe aims of this study are to analyze the risk profile and evaluate the appropriateness of patient referral to coronary CT angiography in a new MSCT laboratory in an academic medical center in a developing country. Methods and ResultsThe study population consisted of 100 consecutive patients (mean age 53 ± 13 years, 83% males) who were referred to the new 64 slice MSCT laboratory at the American University of Beirut between July 2008 and July 2009. 52% of patients had chest pain and 48% were asymptomatic. By the 2006 ACCF criteria, only 8% of the referrals fitted the “Appropriate” criteria, 49% were “Inappropriate”, and 43% were “Uncertain”. The percentage of “Appropriate” indications increased from 8% by the 2006 criteria to 38% by the 2010 ACCF criteria. Framingham risk score (FRS) calculation showed a substantial percentage (46%) of patients to be at low risk, with 32% being at intermediate risk, and 22% at high risk. The prevalence of high calcium score (>400) (0% vs 22%, vs 27%, P < .001) and of obstructive CAD (4% vs 23% vs 40%, P < .001) increased steadily across the low, intermediate, and high FRS groups, respectively. ConclusionsThere was a significant increase in the percentage of “Appropriate” indications for MSCT when comparing the 2010 to the 2006 ACCF appropriateness criteria. However, in spite of that, there was still significant deviation from the ACCF appropriateness criteria among patients referred for coronary CT angiography in this new MSCT laboratory in a developing country.

High-sensitivity C-reactive protein in the low- and intermediate-Framingham risk score groups: Analysis with 18F-fluorodeoxyglucose positron emission tomography

ObjectivesTo evaluate vascular inflammation according to high-sensitivity C-reactive protein (hsCRP) levels in the low- (<10%) and intermediate- (10%–20%) Framingham risk score (FRS) groups using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, which reflects vascular inflammation and vulnerable atherosclerotic plaque. MethodsWe measured hsCRP levels and traditional cardiovascular risk factors in 142 non-diabetic subjects without history of cardiovascular disease. To assess the vascular influence of hsCRP on each FRS category, we compared carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and vascular inflammation, which was represented as the target-to-background ratio (TBR) measured using FDG-PET/CT. ResultsIn both low- and intermediate-FRS categories, mean TBR values in subjects with higher hsCRP levels (≥2mg/L) were significantly increased compared to those with lower hsCRP levels (<2mg/L) (P=0.001, P<0.001, respectively). However, baPWV and CIMT values did not significantly differ according to hsCRP levels in the same FRS categories. Mean TBR levels positively correlated with FRS, body mass index (BMI), whereas negatively correlated with HDL-cholesterol. Multiple stepwise regression analyses showed that hsCRP, LDL-cholesterol, BMI, and insulin resistance were independently associated with mean TBR values (R2=0.414). ConclusionsIn both intermediate and low FRS risk groups, vascular inflammation measured using FDG-PET/CT was increased in individuals with higher hsCRP levels compared to those with lower hsCRP. (Clinicaltrials.gov: NCT01022684).

Prevalence of Abnormal Ankle-Brachial Index Among Individuals With Low or Intermediate Framingham Risk Scores

Purpose To determine the prevalence of an abnormal ankle-brachial index (ABI) among subjects not considered to be at high risk for cardiovascular disease (CVD) based on the Framingham Risk Score (FRS). Materials and Methods Data from the Population-Based Examinations to Determine Ankle-brachiaL index (PEDAL) Study (2007–2009), a cross-sectional study at 23 U.S. sites, in conjunction with Legs for Life, a national ABI screening program, were analyzed. This study includes data from 822 participants (average age 64.3 years ± 11.6, 69.7% women, 89.7% non-Hispanic white) without known CVD or diabetes, who were screened for peripheral artery disease (PAD) with an ABI and for whom all FRS variables were available. Participants' 10-year coronary heart disease (CHD) risk was estimated from the FRS, and three risk categories were defined: low (< 10%), intermediate (10%–19%), and high (≥ 20%). ABI < 0.90 or > 1.4 in either leg was considered abnormal. Results The prevalence of abnormal ABI was 14.2% (95%confidence interval [CI] 11.9%–16.8%). According to the FRS, 463 (56.3%) participants were at low risk, 212 (25.8%) were at intermediate risk, and 147 (17.9%) were at high risk. Among participants with a low FRS (n = 463; without CVD or diabetes or both) and an intermediate FRS (n = 212; without CVD or diabetes or both), 12.3% and 12.2% had an abnormal ABI. Conclusions The prevalence of abnormal ABI, a CHD equivalent, is high among individuals not identified as high risk by conventional Framingham-based risk assessment.

Carotid Ultrasound Identifies High Risk Subclinical Atherosclerosis in Adults with Low Framingham Risk Scores

Conclusion: A high percentage of young to middle-aged individuals with a Framingham Risk Score (FRS) indicating <5% risk of cardiovascular events have abnormal carotid ultrasound findings associated with an increased risk for cardiovascular events. Summary: Atherosclerosis-related clinical events are presumably preceded by a period of asymptomatic atherosclerosis. The FRS is a population-based algorithm recommended to identify at-risk individuals and determine the aggressiveness of preventive therapy (JAMA 2001;285:2486-97). However, population-based risk algorithms do not quantify atherosclerosis. They provide only a probability of cardiovascular events over a relatively short fixed period, usually <10 years. The FRS risk assessment also does not incorporate family history, premature coronary artery disease, remote smoking history, impaired fasting glucose, triglyceride levels, or waist circumference. Tests for subclinical atherosclerosis are therefore sometimes recommended to add incremental information and provide more accurate risk stratification. The authors tested the hypothesis that patients with a low (<5%) FRS 10-year risk for a first cardiovascular event and intermediate (6% to 20%) FRS 10-year risk will have increased cardiovascular risk as determined by an abnormal carotid intima-media thickness (IMT). This study included individuals aged <65 years who were not taking statins and who did not have diabetes or a history of coronary artery disease, but who did undergo a determination of carotid IMT and plaque for primary intervention. Clinical variables analyzed included lipid values, family history of coronary artery disease, FRS, and subsequent pharmacotherapy recommendations. The study comprised 441 individuals who were a mean age of 49.7 ± 7.9 years. Of these patients, 184 (42%, 95% CI, 37.3%-46.5%) had high-risk carotid IMT findings (carotid IMT ≥75th percentile adjusted for age, sex, race, or presence of plaque). In 336 individuals with the lowest FRS score of <5%, 127 (38%, 95% CI, 32.6%-43.0%) had high-risk carotid ultrasound findings. The treating physicians recommended lipid-lowering therapy for 77 individuals (61%) with a FRS ≤5% and high-risk carotid ultrasound findings. Comment: This study indicates a disconnect between the risk assessment by the FRS and carotid IMT. Studies have also found high-risk carotid ultrasound findings influence physicians to prescribe aspirin or lipid-lowering therapies (Wyman RA, et al; Am Heart J 2007;154:1072-7 and Korcarz CE, et al; J Am Soc Echocardiogr 2008;21:1156-62). However, although physicians may make treatment decisions based on a finding of increased carotid IMT, it appears that observing changes in IMT to monitor effects of drug therapy will not reduce subsequent clinical events. A practical point may be that carotid IMT can be used to identify patients at increased risk for cardiovascular events, but once treatment is initiated, subsequent studies to monitor effectiveness of treatment may not be needed.

Improved risk prediction of myocardial Infarction and coronary death based on quantification of subclinical coronary atherosclerosis – Results of the Heinz Nixdorf Recall study

Background: Coronary artery calcium (CAC) has been suggested to improve prediction of coronary events beyond traditional risk factor assessment. We determined whether CAC scoring improves prediction of coronary events when added to traditional risk factor analysis in the general population. Methods: We used data of the Heinz Nixdorf Recall cohort study, including 4129 randomly selected subjects aged 59.4±7.7 years (53% women) without overt coronary artery disease at baseline (2000 to 2003). Traditional risk factors and CAC, measured by electron-beam computed tomography, were assessed. Participants were stratified into low, intermediate or high risk categories using the Framingham risk score (FRS), and modified ATPIII risk score categories (modATPIII). Participants were followed for hard coronary events, i.e. coronary death and non-fatal myocardial infarction for 5.02 years. Results: The cumulative event rate was 2.3% (95% confidence intervals (CI): 1.8–2.8). Relative risks (RR) increased from the lowest to the intermediate and highest FRS and modATPIII risk categories. Crude and modATPIII-adjusted RRs in the highest versus lowest CAC quartile were 6.40 (95% CI: 3.37–12.16) and 4.25 (95% CI: 2.14–8.45), respectively. Adding CAC scores to the FRS and modATPIII-categories significantly improved the areas under the ROC curves from 0.681 and 0.667 to 0.749 (p=0.003) and 0.753 (p=0.0001), respectively. Intermediate modATPIII risk subjects with CAC<100 had an event rate similar to low risk subjects, i.e. 1.5 (95% CI: 0.7–2.6) versus 1.0 (95% CI: 0.7–1.6) (p=0.33). Event rates in intermediate risk subjects with CAC ≥400 were similar to high risk subjects, i.e. 8.9 (95% CI: 5.1–14.3) versus 4.7 (95% CI: 3.3–6.4). Conclusion: CAC scoring improves risk stratification in the general population above and beyond traditional risk factors. Adding CAC scoring to the FRS results in a reclassification improvement of coronary risk, especially when focused on intermediate risk individuals.

Carotid Ultrasound Identifies High Risk Subclinical Atherosclerosis in Adults with Low Framingham Risk Scores

Worldwide, cardiovascular (CV) disease remains the most common cause of morbidity and mortality. Although effective in predicting CV risk in select populations, the Framingham risk score (FRS) fails to identify many young individuals who experience premature CV events. Accordingly, the aim of this study was to determine the prevalence of high-risk carotid intima-media thickness (CIMT) or plaque, a marker of atherosclerosis and predictor of CV events, in young asymptomatic individuals with low and intermediate FRS (<2% annualized event rate) using the carotid ultrasound protocol recommended by the American Society of Echocardiography and the Society of Vascular Medicine. Individuals aged < or = 65 years not taking statins and without diabetes mellitus or histories of coronary artery disease underwent CIMT and plaque examination for primary prevention. Clinical variables including lipid values, family history of premature coronary artery disease, and FRS and subsequent pharmacotherapy recommendations were retrospectively collected for statistical analysis. Of 441 subjects (mean age, 49.7 + or - 7.9 years), 184 (42%; 95% confidence interval, 37.3%-46.5%) had high-risk carotid ultrasound findings (CIMT > or = 75th percentile adjusted for age, gender, and race or presence of plaque). Of those with the lowest FRS of < or =5% (n = 336) (mean age, 48.0 + or - 7.6 years; mean FRS, 2.5 + or - 1.5%), 127 (38%; 95% confidence interval, 32.6%-43.0%) had high-risk carotid ultrasound findings. For individuals with FRS < or = 5% and high-risk carotid ultrasound findings (n = 127; mean age, 47.3 + or - 8.1 years; mean FRS, 2.5 + or - 1.5%), lipid-lowering therapy was recommended by their treating physicians in 77 (61%). Thirty-eight percent of asymptomatic young to middle-aged individuals with FRS < or = 5% have abnormal carotid ultrasound findings associated with increased risk for CV events. Pharmacologic therapy for CV prevention was recommended in the majority of these individuals. The lack of radiation exposure, relatively low cost, and ability to detect early-stage atherosclerosis suggest that carotid ultrasound for CIMT and plaque detection should continue to be explored as a primary tool for CV risk stratification in young to middle-aged adults with low FRS.

Forced vital capacity paired with Framingham Risk Score for prediction of all-cause mortality

Forced vital capacity (FVC) measures lung function and predicts coronary heart disease (CHD); whether it provides additive prediction over CHD risk factors has not been established. We examined whether FVC adds to the prediction of all-cause mortality provided by Framingham Risk Score (FRS) alone. We examined 5,485 (61.1 million projected) nonsmoking adults from the USA who were aged 20-79 yrs. Subjects were from the Third National Health and Nutrition Examination Survey, were without obstructive lung disease, had FVC measurements and had ≤ 12 yrs (mean 8.8 yrs) mortality follow-up. We performed Cox regression analysis to examine whether FVC and forced expiratory volume in 1 s (FEV(1)) (categorised as low ≤ 85% predicted, borderline 86-94% predicted and normal ≥ 95% predicted) within FRS groups (10-yr risk of cardiovascular disease low <10%, intermediate 10-20%, high 20%) predict mortality. Receiver operator characteristic analysis examined whether FVC and FEV(1) added to the prediction provided by FRS. Low-, intermediate- and high-risk FRS groups had 79.5% (n = 4,361), 10.1% (n = 555) and 10.4% (n = 569) persons, respectively. Only the intermediate FRS group showed a graded increase in mortality (10.7, 18.2 and 42.8% per 1,000 person-yrs from highest to lowest FVC categories, respectively); those with low FVC had an almost three-fold greater risk of mortality (hazard ratio 2.64; p<0.01) than those with normal FVC. FVC provided incremental additive value for predicting mortality in addition to FRS for only this group (area under curve 0.65 versus 0.58; p<0.05). Similar results were obtained for FEV(1). Evaluation of lung function may be useful to improve risk stratification in persons with intermediate CHD risk where it adds to prediction of mortality over global risk assessment.

High Prevalence of Ultrasound Detected Carotid Atherosclerosis in Subjects with Low Framingham Risk Score: Potential Implications for Screening for Subclinical Atherosclerosis

The cardiovascular (CV) risk assigned by the Framingham risk score (FRS) misses many subjects destined for CV events. Coronary artery calcification (CAC) as measured by computed tomography and carotid intima-media thickness (CIMT) and plaque assessment using B-mode ultrasound can identify subclinical atherosclerosis. The comparative relation of CAC and CIMT and carotid plaque after integration into the FRS is not established. The aim of this study was to develop a CV screening approach incorporating FRS, CAC, and CIMT. The prevalence of subclinical atherosclerosis, defined as CAC score > 0, CIMT > or = 75th percentile, or plaque > or = 1.5 mm, was determined in the groups with low, intermediate, and high FRS among 136 asymptomatic subjects. The CIMT and CAC values were used to determine "vascular age" and "coronary calcium" age, respectively, with established nomograms. In the 103 low-risk (FRS < 10%) subjects, 41%, 50%, 59%, and 66% had CAC scores > 0, CIMT > or = 75th percentile, plaque > or = 1.5 mm, and CIMT > or = 75th percentile or plaque > or = 1.5 mm, respectively. In the 33 subjects with intermediate (n = 14) or high (n = 19) FRS, 70%, 81%, 87%, and 87% had CAC scores > 0, CIMT > or = 75th percentile, plaque > or = 1.5 mm, and CIMT > or = 75th percentile or plaque > or = 1.5 mm, respectively. Fifty-two percent of subjects with coronary calcium scores of zero had carotid plaque. Adjusted for FRS, body mass index was an independent predictor of abnormal CIMT in the low-FRS group, but not of abnormal CAC. Mean vascular CIMT age was significantly higher than coronary calcium age (61.6 + or - 11.4 vs 58.3 + or - 11.1 years, P = .001), and both were significantly higher than chronologic age (56.9 + or - 10.1 years) (P < .0001 and P < .04, respectively). CIMT upgraded or downgraded FRS by >5% in more cases than CAC (42% vs 17%). In asymptomatic patients without CV disease, CIMT and plaque assessment are more likely to revise FRS than CAC. Body mass index predicts increased CIMT in low-FRS subjects. These findings may have broad implications for screening in low-FRS subjects.

CAROTID ULTRASOUND IDENTIFIES HIGH RISK SUBCLINICAL ATHEROSCLEROSIS IN ADULTS WITH LOW FRAMINGHAM RISK SCORES

Background Worldwide, cardiovascular (CV) disease remains the most common cause of morbidity and mortality. Although effective in predicting CV risk in select populations, the Framingham risk score (FRS) fails to identify many young individuals who experience premature CV events. Accordingly, the aim of this study was to determine the prevalence of high-risk carotid intima-media thickness (CIMT) or plaque, a marker of atherosclerosis and predictor of CV events, in young asymptomatic individuals with low and intermediate FRS ( Methods Individuals aged ≤ 65 years not taking statins and without diabetes mellitus or histories of coronary artery disease underwent CIMT and plaque examination for primary prevention. Clinical variables including lipid values, family history of premature coronary artery disease, and FRS and subsequent pharmacotherapy recommendations were retrospectively collected for statistical analysis. Results Of 441 subjects (mean age, 49.7 ± 7.9 years), 184 (42%; 95% confidence interval, 37.3%-46.5%) had high-risk carotid ultrasound findings (CIMT ≥ 75th percentile adjusted for age, gender, and race or presence of plaque). Of those with the lowest FRS of ≤5% (n = 336) (mean age, 48.0 ± 7.6 years; mean FRS, 2.5 ± 1.5%), 127 (38%; 95% confidence interval, 32.6%-43.0%) had high-risk carotid ultrasound findings. For individuals with FRS ≤ 5% and high-risk carotid ultrasound findings (n = 127; mean age, 47.3 ± 8.1 years; mean FRS, 2.5 ± 1.5%), lipid-lowering therapy was recommended by their treating physicians in 77 (61%). Conclusions Thirty-eight percent of asymptomatic young to middle-aged individuals with FRS ≤ 5% have abnormal carotid ultrasound findings associated with increased risk for CV events. Pharmacologic therapy for CV prevention was recommended in the majority of these individuals. The lack of radiation exposure, relatively low cost, and ability to detect early-stage atherosclerosis suggest that carotid ultrasound for CIMT and plaque detection should continue to be explored as a primary tool for CV risk stratification in young to middle-aged adults with low FRS.

Coronary atherosclerosis: extending to the microcirculation?

This editorial refers to ‘Coronary microcirculatory vasodilator function in relation to risk factors among patients without obstructive coronary disease and low to intermediate Framingham risk score’[†][1], by R. Rubinshtein et al. on page 936 The coronary circulation, responsible for the delivery of oxygen and other nutrients to the myocardium, is a complex system of conductance and resistance vessels. Each has its own mechanisms of dynamic regulation of its calibre through changes in the contractile state of the underlying smooth muscle. In addition, each plays a different role in determining myocardial perfusion in health and disease. The larger epicardial coronary arteries normally offer no significant resistance to blood flow and thus contribute little to the adaptive response of the coronary circulation to the physiological changes in myocardial oxygen demands that occur, for example, during exercise. However, they are the site for the development of coronary atherosclerosis, the best known and most dreaded form of ischaemic heart disease. That atherosclerotic obstructions of the epicardial coronary arterial lumen contribute to the occurrence of myocardial ischaemia and necrosis is easily demonstrable and well accepted. In fact, the diagnosis of ‘coronary artery disease’ is conventionally applied only to patients who are shown to have significant narrowing of one or more major epicardial coronary artery. Although controversies persist regarding their optimal utilization, there is a large armamentarium of therapies available to treat patients with severely narrowed epicardial coronary arteries. These include multiple medications, and percutaneous and surgical revascularization, in many instances supported by the results of randomized clinical trials demonstrating their relative efficacy. The smaller coronary arteries (i.e. too small in calibre to be visualized by angiography) constitute the coronary microcirculation and are those that normally offer significant vascular resistance. Consequently, it is the changes in the calibre of these smaller vessels that determine coronary blood … *Corresponding author. Tel: +1 202 877 9090, Fax: +1 202 877 9034, Email: julio.a.panza{at}medstar.net [1]: #fn-1

Carotid intima-media thickness measurement in cardiovascular screening programmes

Support for the notion that a carotid intima-media thickness (CIMT) measurement is useful in individual cardiovascular risk prediction in addition to a risk function may come from studies showing that for an individual a high or low CIMT measurement leads to a correct shift from one to another risk category and this shift is followed by different treatment consequences. We set out to systematically review the published evidence by performing a PubMed search (2 March 2009). Out of 50 publications on CIMT and future events, 31 reported on the relation in the correct domain, [i.e. those free from symptomatic vascular disease or diabetes mellitus in which assessment of risk using a risk function (e.g. Framingham or SCORE) to base initiation of drug treatment upon is recommended]. Most studies reported relative risks (or equivalents) for the entire population only, and no information on relative risks within certain risk categories that may be of use to reclassify individuals based on combination of absolute and relative risks. No data on potential shifts of participants was presented. Eight studies specifically focused on the added value of CIMT in risk prediction. In seven studies the area under the curve (AUC) of a receiver operating characteristic was used to assess improvements in risk prediction. These analyses showed that addition of a CIMT measurement to established risk factors led to small and sometimes significant improvements in the AUC. However, change in AUC should not be the only parameter to rely on to judge the appropriateness of CIMT in risk stratification. In one study (n = 242), evidence was presented in participants with an intermediate Framingham risk score, a CIMT measurement above the 60th (men) and 80th (women) percentile of age-specific normal CIMT values, shifted participants above the threshold for initiation of drug therapy. Yet, the study was based on 24 events, and no information was presented on the proportion of participants correctly shifted. At present it seems that the published evidence to quantitatively support the use of a CIMT measurement to help in risk stratification on top of a risk function is limited.

Prevalence and Distribution of Sub-Clinical Atherosclerosis by Screening Vascular Ultrasound in Low and Intermediate Risk Adults: The New York Physicians Study

Many persons experiencing cardiovascular disease (CVD) events are not at high calculated CVD risk by Framingham risk score. The identification of carotid and femoral plaque has been associated with CVD events. In this study, the prevalence of plaques in adults at low and intermediate risk was examined. Asymptomatic patients without CVD (n = 715; 43% women) were screened for carotid and femoral plaque using B-mode ultrasound. Significant predictors of plaque were male gender and age and, among women, dyslipidemia. Overall plaque prevalence was 32.8% among women and 40.5% among men aged 50 to 64 years. Among subjects with plaque in this age group, 56% of women and 31% of men had plaque exclusively in the femoral artery and would have been missed if only carotid ultrasound had been performed. Ultrasound screening of the carotid and femoral arteries in a population with low and intermediate Framingham risk scores can identify potentially high risk subjects for whom intensive CVD risk factor modification may be appropriate.

Mis-SHAPEing Public Health Policy

On June 19, 2009, the Heart Attack Prevention Bill, a bill mandating health insurance coverage of radiographic screening tests to detect asymptomatic atherosclerosis, was passed through the Texas legislature and enacted in September.1 The bill, written by the SHAPE (Screening for Heart Attack Prevention and Education) Task Force and championed by Representative Rene O. Oliveira, was first introduced in 2007, but failed at that time because of a lack of scientific data. However, without further evidence or modification, the bill was recently reintroduced and passed, requiring health insurance companies to cover the costs for either cardiac computed tomography (CT) scan to measure coronary artery calcium score or ultrasound to measure carotid artery intimal thickness every 5 years for all men aged 45 to 75 and women aged 55 to 75, along with persons of any age who have diabetes mellitus or an intermediate Framingham Risk Score.1 The Heart Attack Prevention Bill introduces complex questions about the level of scientific evidence needed to support legislative mandates for medical coverage. Neither screening test has demonstrated clinical efficacy in preventing acute myocardial infarctions nor is supported as a primary prevention strategy by any of the major guideline committees.2 In the absence of validating data, mandating medical coverage for these procedures raises concerns of unwarranted costs or harm to patients and potential for conflicts of interest. This article (1) considers the rationale for mandating insurance coverage, (2) considers criteria for evaluating the merits of such policies, and (3) applies these criteria to evaluate the rationale and merits of the Heart Attack Prevention bill, including the political, economic, and social forces at play. As health coverage and payment reform efforts gain increasing momentum, it is critical that legislative coverage mandates qualify as effective public health policy. Currently, most health insurance coverage decisions …

Prevalence of coronary artery disease across the Framingham risk categories: coronary artery calcium scoring and MSCT coronary angiography

BackgroundNon-invasive assessment of subclinical atherosclerosis by means of coronary artery calcium scoring (CACS) and multi-slice computed tomography (MSCT) coronary angiography could improve patients’ risk stratification. However, data relating observations on CACS and MSCT coronary angiography to traditional risk assessment are scarce. Methods and ResultsIn 314 consecutive outpatients (54 ± 13 years, 56% males) without known CAD, CACS and 64-slice MSCT coronary angiography were performed. According to the Framingham risk score (FRS), 51% of patients were at low, 24% at intermediate and 25% at high risk, respectively. MSCT angiograms showing atherosclerosis were classified as showing obstructive (≥50% luminal narrowing) CAD or not. Both CACS and MSCT coronary angiography showed a high prevalence of normal coronary arteries in low FRS patients (70% and 61%, respectively). An increase in the prevalence of CACS >400 (4% low vs 19% intermediate vs 36% high), CAD (39% low vs 79% intermediate vs 91% high), and obstructive CAD (15% low vs 43% intermediate vs 58% high) was observed across the FRS categories (P < .0001 for all comparisons). ConclusionsA strong positive relationship exists between FRS and the prevalence and extent of atherosclerosis. Especially in intermediate FRS patients, CACS and MSCT coronary angiography provide useful information on the presence of subclinical atherosclerosis.

Abstract 5807: First Demonstration that Coronary CT Angiography Reveals Coronary Arterial Vessel Wall Thickening in Patients with Intermediate and High Framingham Risk Score

Introduction. Early atherosclerosis is characterized by vessel-wall thickening with preserved lumen size. Contrast-enhanced coronary artery computed tomography (CTA) has been validated for stenosis detection and characterization of atherosclerotic plaques but vessel wall thickening in patients with high Framingham risk score (FRS) has not been shown. We hypothesized that increased mean percent vessel wall area (PVWA) and remodeling index (RI) reflect early vessel wall thickening in subjects with higher FRS, with preservation of luminal size. Methods. We assessed 25 patients with coronary CTA using a validated, highly standardized approach on a commercial post processing workstation (Vitrea; SurePlaque 4.0). FRS was calculated by standard criteria. We evaluated 153 segments in patients with low FRS (&lt;10%) and 35 segments in patients with intermediate-high FRS (&gt;10%). Mean minimal lumen diameter (MLD), minimal lumen area (MLA), remodeling index (RI), and PVWA were compared with unpaired t-test in patients with low versus &gt;10% FRS. Mean PVWA was calculated as follows: (total vessel area-lumen area)/total vessel area. p-value &lt;0.05 was considered significant. Results. In all patients, mean FRS was 7%; 20 patients had FRS&lt;10% and 5 had FRS&gt;10%. PVWA and RI were significantly higher in the intermediate-high FRS group compared to low FRS (0.46±0.07 vs 0.42±0.07; p=0.04 and 0.97±0.15 vs 0.92±0.13; p=0.004, respectively), while MLD/MLA were similar (Figure 1 ). Conclusions. This is the first demonstration that coronary CTA can detect vessel wall thickening with preserved lumen size in patients with FRS&gt;10%. Figure 1. Cross sectional image demonstrating normal wall thickness (A). Cross sectional image demonstrating increased wall thickness (B). Bar graph demonstrating significant difference in PVWA between low and intermediate-high Framingham risk groups (C). Bar graph demonstrating significant difference in RI between low and intermediate-high Framingham risk groups (D).

Genetic variation at the 9p21 locus predicts angiographic coronary artery disease prevalence but not extent and has clinical utility

Variants at the 9p21 locus have been associated with coronary heart disease, but their precise disease phenotype and utility for clinical risk assessment are uncertain. Consenting patients with early-onset angiographic coronary artery disease (CAD) (n = 1,011) were compared with matched subjects (n = 545) free of angiographic disease and with a random population sample (n = 565). Cases and controls were genotyped for 4 variants, and ORs for angio-CAD were determined. Findings were validated in a separate set of cases and controls (n = 1,452). Alleles were highly correlated (r(2) > or = 0.9), and all predicted angio-CAD compared with both control groups. Genotype at rs2383206 (minor allele frequency 45.9%), the most predictive (P < .0001), was associated with an adjusted odds ratio for angio-CAD of 1.39 (95% CI, 1.05-1.85) for heterozygote and 1.73 (1.26-2.37) for homozygote risk-allele carriers and explained 21% of population attributable risk and was independent of traditional risk factors and myocardial infarction. For the comparison of combined cases versus combined control samples (N = 3,573), CAD was predicted by high-risk allele homozygosity at P = 9 x 10(-8). Despite this, extent of disease was not increased. Applied to patients with intermediate Framingham risk scores, 9p21 genotyping modified risk classification in 24%. Variants at the 9p21 locus robustly predict angiographic CAD prevalence, independent of standard risk factors, but not CAD extent or myocardial infarction; provide pathophysiological insights; and may be clinically useful in refining coronary heart disease risk classification.

Defining Normal Distributions of Coronary Artery Calcium in Women and Men (from the Framingham Heart Study)

Coronary artery calcium (CAC) may improve risk stratification for patients with coronary heart disease (CHD) beyond traditional risk factors. Subjects from the Framingham Heart Study Offspring and Third Generation cohorts (48% women; mean age 53 years) underwent noncontrast electrocardiographically triggered cardiac multidetector computed tomography. The prevalence of absolute CAC (Agatston score [AS] >0, >100, and >400) and relative age- and gender-specific strata (25th, 50th, 75th, 90th, and 95th percentiles) were determined in a healthy subset free of clinically apparent cardiovascular disease or CHD risk factors (n = 1,586), the overall sample at risk (n = 3,238), and subjects at intermediate Framingham risk score (FRS; 6% to 20% 10-year CHD event risk; n = 1,177). Absolute AS and relative cutoffs for CAC increased with age and FRS, were higher in men compared with women in each of the 3 cohorts, and increased from the healthy subset to the overall cohort to subjects at intermediate risk. However, in subjects with CAC, there was substantial disagreement between absolute and relative cut-off values for labeling subjects as having increased CAC. In general, more subjects were considered to have increased CAC using relative cut-off values, especially in women and younger subjects. Fewer subjects at intermediate FRS had increased CAC using comparable absolute versus relative cutoffs (men 32% at AS >100 vs 36% at >75th percentile; women 24% at AS >100 vs 34% at >75th percentile). In conclusion, we provided distributions of CAC in a healthy subset, the overall cohort, and subjects at intermediate risk from the Framingham Heart Study for both absolute and relative cut-off values for CAC. Absolute cutoffs underestimated the proportion of subjects with increased CAC, specifically in women, younger persons, and persons at intermediate CHD risk.

Association of Coronary Atherosclerosis Detected by Multislice Computed Tomography and Traditional Risk-Factor Assessment

Framingham risk score is an office-based tool used for long-term coronary heart disease risk stratification. Most acute coronary events occur in association with proximal nonobstructive atherosclerotic plaque. Multislice computed tomography detects both obstructive coronary artery disease (CAD) and proximal atherosclerotic plaque with high accuracy. The association of Framingham risk score with obstructive CAD and proximal atherosclerotic plaque was tested. Coronary multislice computed tomography was performed in 295 patients (61% men, mean age 54 +/- 13 years) without documented CAD referred for evaluation of cardiac symptoms. Framingham risk score was computed and patients were stratified according to 10-year risk (n = 213 [72%] low, n = 74 [25%] intermediate, and n = 8 [3%] high). Obstructive CAD was defined as > or =50% stenosis in > or =1 epicardial coronary artery. Proximal atherosclerotic plaque was defined as calcified or noncalcified plaque in the left main or proximal left anterior descending artery. In the low- and intermediate-Framingham risk score groups, there was a high frequency of proximal atherosclerotic plaque (44% and 75%) and obstructive CAD (16% and 34%), although both findings were more prevalent in the high-Framingham risk score group (63% for atherosclerotic plaque, 88% for obstructive CAD), respectively. Proximal atherosclerotic plaque was noncalcified in approximately 13 of patients. In women (n = 114) and younger (<55 years) patients (n = 148), most (93% and 91%, respectively) had a low Framingham risk score. There were 48 women and 51 younger patients with proximal atherosclerotic plaque, of whom only 40% (in each group) were on statin therapy. In conclusion, of patients with a low and intermediate Framingham risk score, a significant proportion had proximal atherosclerotic plaque or obstructive CAD.

Incremental predictive value of vascular assessments combined with the Framingham Risk Score for prediction of coronary events in subjects of low–intermediate risk

Background:In patients with low–intermediate risk, the use of the Framingham Risk Score (FRS) may not allow accurate prediction of the occurrence of coronary events.Objective:To determine whether non-invasive vascular sonographic assessments...