Traditional Risk Factor Assessment Research Articles

Genetic polymorphism in Methylenetetrahydrofolate Reductase chloride transport protein 6 (MTHFR CLCN6) gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients.

BackgroundRenal transplant recipients (RTRs) are at increased risk of keratinocyte cancer (KC), especially cutaneous squamous cell carcinoma (cSCC). Previous studies identified a genetic variant of the Methylenetetrahydrofolate Reductase (MTHFR) gene, C677T, which conferred a risk for diagnosis of cSCC in Irish RTRs.ObjectiveWe sought to find further genetic variation in MTHFR and overlap genes that may be associated with a diagnosis of KC in RTRs.MethodsGenotyping of a combined RTR population (n = 821) from two centres, Ireland (n = 546) and the USA (n = 275), was performed. This included 290 RTRs with KC and 444 without. Eleven single nucleotide polymorphisms (SNPs) in the MTHFR gene and seven in the overlap gene MTHFR Chloride transport protein 6 (CLCN6) were evaluated and association explored by time to event analysis (from transplant to first KC) using Cox proportional hazards model.ResultsPolymorphism at MTHFR CLCN6 (rs9651118) was significantly associated with KC in RTRs (HR 1.50, 95% CI 1.17–1.91, p < 0.00061) and cSCC (HR 1.63, 95% CI 1.14–2.34, p = 0.007). A separate SNP, MTHFR C677T, was also significantly associated with KC in the Irish population (HR 1.31, 95% CI 1.05–1.63, p = 0.016), but not American RTRs.ConclusionsWe report the association of a SNP in the MTHFR overlap gene, CLCN6 and KC in a combined RTR population. While the exact function of CLCN6 is not known, it is proposed to be involved in folate availability. Future applications could include incorporation in a polygenic risk score for KC in RTRs to help identify those at increased risk beyond traditional risk factor assessment.

Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring: the ROBINSCA trial.

Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n = 14450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12185 participants (84.2%) in arm A and 12950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE < 10%), 26.5% at intermediate risk (SCORE 10-20%), and 28.4% at high risk (SCORE ≥ 20%). According to CAC screening, 76.0% were at low risk (Agatston < 100), 15.1% at high risk (Agatston 100-399), and 8.9% at very high risk (Agatston ≥ 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. NTR6471.

Promoting Cardiovascular Health in Midlife Women

Cardiovascular disease (CVD) remains the number one cause of death in the USA. In women, coronary heart disease (CHD) accounts for 22% of deaths with an additional 6.2% of deaths secondary to stroke. The prevalence of CVD increases as women age; after the age of 75, the incidence will exceed that reported for men. The risk for CVD in women is systematically underestimated. Both healthcare providers and women need a better understanding of the mechanism and role of traditional CVD risk factors (CVDRF) in women, and the newer identified non-traditional CVDRF which are unique to women and the resulting CVD morbidity and mortality. Women with a CVD event often do not present the same as men. During middle-age and the transition to post-menopause, the complaints women experience often do not match the standard male-oriented CVD symptoms, and thus are often erroneously attributed to menopause. Unique sex-gene expression and function account for the biological variances in both CVDRF and CVD prevalence and presentation in women. There is a need for a more sex-specific approach to CVDRF assessment and targeted reduction in women. There are major differences in the risk, development, and presentation of CVD in women. A wide-spread awareness is lacking in women and healthcare providers of the unique sex-specific differences in both CVDRF and CVD in women. The traditional CVD risk factor assessment tools and CVD risk calculators do not account for these differences and systematically underestimate CVD risk in women.

Negative Risk Markers for Cardiovascular Events in the Elderly

BackgroundCardiovascular risk increases dramatically with age, leading to nearly universal risk-based statin eligibility in the elderly population. To limit overtreatment, elderly individuals at truly low risk need to be identified. ObjectivesDiscovering “negative” risk markers able to identify elderly individuals at low short-term risk for coronary heart disease and cardiovascular disease. MethodsIn 5,805 BioImage participants (mean age 69 years; median follow-up 2.7 years), the authors evaluated 13 candidate markers: coronary artery calcium (CAC) = 0, CAC ≤10, no carotid plaque, no family history, normal ankle-brachial index, test result <25th percentile (carotid intima-media thickness, apolipoprotein B, galectin-3, high-sensitivity C-reactive protein, lipoprotein(a), N-terminal pro–B-type natriuretic peptide, and transferrin), and apolipoprotein A1 >75th percentile. Negative risk marker performance was compared using patient-specific diagnostic likelihood ratio (DLR) and binary net reclassification index (NRI). ResultsCAC = 0 and CAC ≤10 were the strongest negative risk markers with mean DLRs of 0.20 and 0.20 for coronary heart disease (i.e., ≈80% lower risk than expected from traditional risk factor assessment) and 0.41 and 0.48 for cardiovascular disease, respectively, followed by galectin-3 <25th percentile (DLR 0.44 and 0.43, respectively) and absence of carotid plaque (DLR 0.39 and 0.65, respectively). Results obtained by other candidate markers were less impressive. Accurate downward risk reclassification across the Class I statin-eligibility threshold defined by the American College of Cardiology/American Heart Association was largest for CAC = 0 (NRI 0.23) and CAC ≤10 (NRI 0.28), followed by galectin-3 <25th percentile (NRI 0.14) and absence of carotid plaque (NRI 0.08). ConclusionsElderly individuals with CAC = 0, CAC ≤10, low galectin-3, or no carotid plaque had remarkable low cardiovascular risk, calling into question the appropriateness of a treat-all approach in the elderly population.

Reclassification of coronary heart disease risk in a primary prevention setting: traditional risk factor assessment vs. coronary artery calcium scoring.

In a primary prevention screening program of asymptomatic middle-aged subjects, we sought to assess the degree of risk-reclassification provided by traditional risk assessment vs. coronary artery calcification scoring (CACS). A total of 1,806 consecutive asymptomatic subjects (age 55 years, 76% men), who underwent comprehensive screening in a primary prevention clinic between 3/2016 and 9/2017 were included. Standard risk factors, C-reactive protein (CRP) and CAC scoring were performed. % 10-year coronary heart disease (CHD) risk was calculated using Reynolds Risk Score (RRS), atherosclerotic cardiovascular disease (ASCVD) score and multiethnic study on subclinical atherosclerosis (MESA) CACS were calculated. % 10-year CHD risk for all scores was categorized as follows: <1%, 1-5%, 6-10% and >10%. Mean CRP, RRS, ASCVD and MESA-CACS were 2.1±4.2, 3.7±4, 4.9±6, 4.9±5; 54% had CAC of 0, while 21% had CAC >75th percentile. There was a significant, but modest correlation between MESA-CAC score and (I) RRS (r=0.62) and (II) ASCVD scores (r=0.65, both P<0.001). Compared to MESA-CAC, for RRS, (I) 188 (10%) patients had a downgrade in risk and (II) 538 (30%) patients had an upgrade in risk (40% reclassification of risk). Similarly, compared to MESA-CAC, for ASCVD score, (I) 412 (23%) patients had a downgrade in risk and (II) 329 (18%) patients had a downgrade in risk (41% reclassification of risk). In a primary prevention screening program of asymptomatic middle-aged patients, RRS overestimates and ASCVHD underestimates 10-year CHD risk vs. MESA-CACS. Addition of CACS results in significant risk reclassification.

P622Reclassification of 10-year coronary heart disease risk in a primary prevention setting: traditional risk factor assessment vs. coronary artery calcium scoring

P622Reclassification of 10-year coronary heart disease risk in a primary prevention setting: traditional risk factor assessment vs. coronary artery calcium scoring

Imaging to Assess Ischemic Heart Disease in Women.

Ischemic heart disease is a leading cause of morbidity and mortality for women and men around the world. However, traditional cardiovascular risk factors do not fully capture cardiac risk in women. This review summarizes sex-based differences in the clinical presentation, pathophysiology, and risk assessment of ischemic heart disease. We also examine the use of anatomic and functional imaging modalities in the diagnosis of ischemic heart disease in women. Recent studies with women subjects have bolstered the predictive value of the coronary artery calcium (CAC) score in predicting atherosclerotic cardiovascular disease risk and major adverse cardiac events in a graded fashion. In addition, combined CAC scoring and coronary computed tomography (CCTA) has shown promise in excluding coronary artery disease (CAD). Using CCTA, data have suggested that increasing cardiovascular risk factors are associated with an increase in noncalcified coronary plaque in women compared with an increase in both calcified and noncalcified plaque in men with cardiac risk factors. Some data have suggested that women obtain greater prognostic benefit from CCTA than from other noninvasive tests. Fractional flow reserve obtained from a CCTA (FFRCT) is a new mathematical assessment of coronary blood flow that determines the presence of lesion-specific myocardial ischemia. Prevention and identification of ischemic heart disease remains a foundation of cardiology and public health. In women, atypical symptoms and limitations in traditional risk factor assessment lead to challenges in the identification of ischemic heart disease. With improvements in technologies such as CAC scoring, CCTA, instantaneous flow reserve (iFR), optical coherence tomography (OCT), and FFRCT, there is great promise for identification of ischemic heart disease, and the future of prevention in women. Future studies with strong female representation should investigate the role of novel imaging techniques in women.

Impact of Lipid Measurements in Youth in Addition to Conventional Clinic-Based Risk Factors on Predicting Preclinical Atherosclerosis in Adulthood

Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult nonlaboratory-based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a lipid model based on nonlaboratory risk factors plus lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood. The study comprised 2893 participants 12 to 18 years of age from 4 longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study), and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up, 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age and sex were included in each model. In univariate models, all risk factors except for borderline high and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (relative risk [95% confidence interval]), male sex (2.7 [2.0-2.6]), prehypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3-2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high low-density lipoprotein cholesterol (1.6 [1.2-2.2]), high low-density lipoprotein cholesterol (1.6 [1.1-2.1]), and borderline low high-density lipoprotein cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT (P<0.05). The addition of lipids into the nonlaboratory risk model slightly but significantly improved discrimination in predicting high cIMT compared with nonlaboratory-based risk factors only (C statistics for laboratory-based model 0.717 [95% confidence interval, 0.685-0.748] and for nonlaboratory 0.698 [95% confidence interval, 0.667-0.731]; P=0.02). Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic-based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood.

Abstract 705: Coronary Artery Calcification and Cardiovascular Risk Factors in South Asians

Compared to other ethnic groups, South Asians are at higher risk for cardiovascular disease and diabetes mellitus. Traditional risk factor assessment, developed mainly in a white European-descent populations, may underestimate the incidence of cardiovascular disease in South Asians. Our study examined the relationship between coronary calcification, a strong predictor of cardiovascular events, and other traditional cardiovascular risk factors in South Asians. We analyzed the association of coronary calcification with both traditional and emerging factors commonly used to predict cardiovascular risk. These factors include the lipid panel (total cholesterol, LDL-C, HDL-C, and triglycerides), fasting blood glucose, high-sensitivity CRP, family history of coronary artery disease and diabetes, and the ACC/AHA-recommended atherosclerotic cardiovascular disease (ASCVD) risk score. We found that fasting blood glucose, glycated hemoglobin, insulin, BMI, and personal history of hypertension, hypercholesterolemia, and diabetes mellitus were all significantly associated with a non-zero calcium score. High-sensitivity CRP, the conventional lipid panel, the ASCVD risk score, and family history of coronary artery disease and diabetes were not. Because the lipid panel was not predictive while the glucose dysmetabolism risk factors were, the evaluation of South Asians should include and focus on pre-diabetic risk factors, such as fasting blood glucose, insulin, and hemoglobin A1c, and measurements of obesity.

Contribution of cardiorespiratory fitness, relative to traditional cardiovascular disease risk factors, to common carotid intima-media thickness.

Studies have suggested that being slightly overweight but fit is better for cardiovascular health than being somewhat leaner but unfit. Here, we sought to determine the contribution of cardiorespiratory fitness (CRF), relative to the presence of risk factors, to common carotid intima-media thickness (CIMT), a measurement of atherosclerosis and cardiovascular disease risk. Data were analysed from a cohort of 7300 German employed individuals aged 46 (±7)years who participated in a preventive health check-up at a specialized prevention centre. In addition to traditional cardiovascular disease risk factor assessment, participants performed an exercise test with spirometry to exhaustion, and common CIMT was measured. Individuals were defined as being fit or unfit based on the median age- and sex-specific relative maximum oxygen consumption. In a multivariable analysis, there was a strong inverse association between CRF and common CIMT. Individuals who were considered fit and did not have any cardiovascular disease risk factors had the lowest common CIMT values (reference group). Those who were unfit and had an increased risk factor level always had the highest common CIMT values. Good CRF partly compensated for the increased common CIMT due to a risk factor. However, unfit individuals without increased risk factor levels had a common CIMT that was not significantly different from that of the reference group, whereas fit individuals who smoked, had a high body mass index, a low HDL cholesterol concentration or a high systolic blood pressure had an increase in common CIMT. Cardiorespiratory fitness is a major determinant of common CIMT. Improved CRF does slightly, but not completely, abolish the adverse consequences of cardiovascular disease risk factors on common CIMT.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment.

Echoing the Appropriate Use Criteria

Cardiovascular disease (CVD) is the leading cause of death in developedcountries, andmanywhodie suddenlyofCVDhave no previous symptoms.1 Therefore, there is great interest in identifying at-risk individuals so that appropriate preventive measurescanbe implemented.All asymptomaticadults should undergo global risk assessment. For carefully selected individuals deemed at intermediate risk, noninvasive imagingmethods formeasuring coronary artery calcium level or carotid intima–media thickness are additional tools for risk stratification,with class IIa indications (benefits exceed risks) in the 2010 American College of Cardiology Foundation/ AmericanHeart Association guidelines.2 Althoughpredictive of risk above traditional risk factor assessment, it remains untested whether risk assessment with these or other tests directly produces changes in management that improve outcomes. Transthoracic echocardiography is a widely used tool for the diagnosis and management of CVD. Most echocardiograms are ordered by primary care physicians rather than cardiologists.3 Population-based investigationsof asymptomatic individuals screenedbyechocardiographyhave foundthat incidental findings, suchas asymptomatic left ventricular (LV) dysfunction and LV hypertrophy, can predict cardiovascular and all-cause mortality independent of blood pressure and other risk factors.2 TheAmericanCollege of CardiologyFoundation/AmericanHeartAssociationguidelinesgive restingechocardiography screening a class IIb indication (benefit somewhat better than risk) for thedetectionof LVhypertrophy and LVdysfunction forasymptomaticadultswithhypertensionbut aclass III (nobenefit) for thosewithouthypertension.2Todate, no studies have examined whether a patient’s knowledge of his or her echocardiogram results, including LV hypertrophy, improves adherence topreventivemeasures and lifestyle recommendations. Among Medicare-recipient patients, there has been increaseduseof noninvasive and invasive cardiac services from 1993 to2011,notexplainedbychanges inCVDprevalence.4Cardiovascular diseasemortality has also declined between 1997 and 2007 by 26%, although the burden of CVD remains high.1 In response to the growinguse of echocardiography (about an 8% annual increase3), the American Society of Echocardiography in 2011updated their appropriateuse criteria (AUC) consensus statement.5 Since then, AUC have been a focus for accreditation societies and payers alike to improve quality and curtail medical expenses. The AUC for echocardiography are mostly basedon expert consensus andobservational data because randomized clinical trial data testing the usefulness of echocardiography-guided compared with nonguided management were unavailable for most indications. Hypertrophic cardiomyopathy is present in 1 in 500of the general population and is themost frequent cause of sudden cardiacdeath inyoungpeople (including trainedathletes). After the introductionofapreparticipationathletic screeningprogram in Italy (first with physical examination and an electrocardiogram,and thenechocardiography ifneeded), adeclining incidenceof suddencardiacdeath inathleteswasnoted.6However, the AUC by the American Society of Echocardiography do not endorse routine echocardiography screening for athletes participating in competitive sports who have normal results on a cardiovascular examination.5 The role for cardiovascular screening of presumably healthy athletes remains controversial givengenerally lowratesof suddencardiacdeath in this population. In this issue of JAMA Internal Medicine, Lindekleiv et al7 present results from the Tromso cohort, a population-based study conducted in Norway. During their fourth survey, participants were randomly allocated to 1 of 2 types of examination. This design essentially randomized unselected, generallymiddle-aged, individuals toastrategyofechocardiography screening vs no echocardiography. This was not designed as a clinical trial, nor was the usefulness of echocardiography screening for mortality their a priori hypothesis. Of 3272 participants allocated to echocardiography, 362had findings that met the referral criteria for cardiology, and 290 (8.9%) were newly evaluated as a result of screening. Significant incidental findingsnoted includedmyxoma,LVdysfunction,wallmotion abnormality, andvalvular disease. Despite cardiology referral for these diagnoses,mortality during 15 follow-upyears was unchanged between the screened and nonscreened groups. Therewasno reduction in incidentmyocardial infarction or stroke, but other morbidity outcomes, such as freedomfromcardiac surgery (perhaps for valvular disease),were not examined. During the Tromso Study fourth examination, 6727 individuals underwent carotid screening.8 It is unclear howmany of these individuals also had echocardiography. If these individualswere in thenoechocardiogramtreatment arm, the authors may be comparing echocardiography with other types Related article page 1592 Research Original Investigation Echocardiographic Screening and Long-term Survival

The association of brachial artery flow-mediated dilation and long-term cardiovascular events in subjects without heart disease

Background: Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. Methods and results: To find out the long-term association of brachial artery Flow-Mediated Dilation (FMD) and long-term adverese cardiovascular (CV) events, we prospectively assessed brachial artery FMD, using high-resolution linear array ultrasound, in 618 consecutive healthy subjects without heart disease: 387 (63%) men, mean age 54±11 years and body mass index 28±4 kg/m2. Subjects were divided into 2 groups: ≤ (n=309) and > (n=309) the median %FMD of 11.3%. Both groups were comparable in regard to traditional cardiovascular risk factors, lipoproteins, fasting glucose, high-sensitivity C-reactive protein, concomitant medications and Framingham 10-year risk score. In a mean clinical follow-up of 4.6±1.8 years the composite CV events (all-cause mortality, non-fatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneus coronary interventions) were significantly more common in subjects with FMD ≤ rather than > the median of 11.3% (14.2% vs 1.0%, p=0.0001). Univariate analysis demonstrated that the median FMD significantly predicted CV events \[odds ratio (OR) of 2.78 and 95% CI (1.35 to 5.71) (p=0.003)]. Multivariate analysis controlling for traditional cardiovascular risk factors demonstrated that median FMD was the best independent predictor of long-term CV events [OR 2.93, 95% CI 1.28 to 6.68 (p=0.011)\] (Figure). ![Figure][1] Conclusions: Brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment. [1]: pending:yes

Ischemic Heart Disease in Women

Cardiovascular disease is the leading cause of death in women. Although overall mortality from coronary heart disease (CHD) has decreased, there are subsets of patients, particularly young women, in whom the mortality rate has increased. Underlying sex differences in CHD may be an explanation. Women have more frequent symptoms, more ischemia, and higher mortality than men, but less obstructive coronary artery disease (CAD). Despite this, traditional risk factor assessment has been ineffective in risk stratifying women, prompting the emergence of novel markers and prediction scores to identify a population at risk. Sex differences in manifestations and the pathophysiology of CHD also have led to differences in the selection of diagnostic testing and treatment options for women, having profound effects on outcomes. The frequent finding of nonobstructive CAD in women with ischemia suggests microvascular dysfunction as an underlying cause; therefore, coronary reactivity and endothelial function testing may add to diagnostic accuracy in female patients. In spite of evidence that women benefit from the same therapies as men, they continue to receive less-aggressive therapy, which is reflected in higher healthcare resource utilization and adverse outcomes. More sex-specific research is needed in the area of symptomatic nonobstructive CAD to define the optimal therapeutic approach.

LIFETIME RISK ALGORITHM IDENTIFIES MORE PATIENTS WITH CAROTID AND FEMORAL PLAQUES THAN 10 YR OR 30 YR FRAMINGHAM RISK ALGORITHMS

•Mortality from ischemic cardiovascular disease (CVD) is epidemic in the US, with a million cardiovascular deaths and 770,000 first coronary attacks every year. First coronary attacks have a 38% mortality within the first year (American Heart Association Heart and Stroke Facts, 2008) • Traditional risk factor assessment analysis will identify only 50% of those with disease (Kannel WB et al. American Heart J. 2004, 148:16-26) • Yet among patients with fatal and non-fatal MIs, 90% have a remediable risk factor (Greenland P et al. JAMA 2003, 290: 891-7) •Atherosclerosis is commonly found in more than one vascular bed (Allison MA et al., ATVB 2004) •CAFES-CAVE Study showed that even very low risk populations had significant cardiovascular disease and that carotid (CP) and femoral plaque (FP) predict cardiovascular events (Belcaro G et al. Atherosclerosis 2001, 156:379-387) • Current CVD prediction algorithms utilize traditional risk factors in populations but have failed to identify those at highest risk due to underlying disease. We compared a newer algorithm, “Lifetime Risk” (LR), with 10-yr and 30-yr Framingham Risk Score (FRS) algorithms as to their ability to identify those subjects at highest risk because of initial CVD event, based on having carotid or femoral artery plaque.

Screening for Ischemic Heart Disease with Cardiac CT: Current Recommendations.

Cardiovascular disease remains the leading cause of mortality in the US and worldwide, and no widespread screening for this number one killer has been implemented. Traditional risk factor assessment does not fully account for the coronary risk and underestimates the prediction of risk even in patients with established risk factors for atherosclerosis. Coronary artery calcium (CAC) represents calcified atherosclerosis in the coronary arteries. It has been shown to be the strongest predictor of adverse future cardiovascular events and provides incremental information to the traditional risk factors. CAC consistently outperforms traditional risk factors, including models such as Framingham risk to predict future CV events. It has been incorporated into both the European and American guidelines for risk assessment. CAC is the most robust test today to reclassify individuals based on traditional risk factor assessment and provides the opportunity to better strategize the treatments for these subjects (converting patients from intermediate to high or low risk). CAC progression has also been identified as a risk for future cardiovascular events, with markedly increased events occurring in those patients exhibiting increases in calcifications over time. The exact intervals for rescanning is still being evaluated.

Circulating Troponin As Measured by a Sensitive Assay for Cardiovascular Risk Assessment in Primary Prevention

Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. We measured circulating concentrations of cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardiovascular events (MACE) during 5 years of follow-up. Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

Screening Asymptomatic Adults With Resting or Exercise Electrocardiography: A Review of the Evidence for the U.S. Preventive Services Task Force

Coronary heart disease is the leading cause of death in adults. Screening for abnormalities by using resting or exercise electrocardiography (ECG) might help identify persons who would benefit from interventions to reduce cardiovascular risk. To update the 2004 U.S. Preventive Services Task Force evidence review on screening for resting or exercise ECG abnormalities in asymptomatic adults. MEDLINE (2002 through January 2011), the Cochrane Library database (through the fourth quarter of 2010), and reference lists. Randomized, controlled trials and prospective cohort studies. Investigators abstracted details about the study population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria. No study evaluated clinical outcomes or use of risk-reducing therapies after screening versus no screening. No study estimated how accurately resting or exercise electrocardiography classified participants into high-, intermediate-, or low-risk groups, compared with traditional risk factor assessment alone. Sixty-three prospective cohort studies evaluated abnormalities on resting or exercise ECG as predictors of cardiovascular events after adjustment for traditional risk factors. Abnormalities on resting ECG (ST-segment or T-wave abnormalities, left ventricular hypertrophy, bundle branch block, or left-axis deviation) or exercise ECG (ST-segment depression with exercise, chronotropic incompetence, abnormal heart rate recovery, or decreased exercise capacity) were associated with increased risk (pooled hazard ratio estimates, 1.4 to 2.1). Evidence on harms was limited, but direct harms seemed minimal (for resting ECG) or small (for exercise ECG). No study estimated harms from subsequent testing or interventions, although rates of angiography after exercise ECG ranged from 0.6% to 2.9%. Only English-language studies were included. Statistical heterogeneity was present in several of the pooled analyses. Abnormalities on resting or exercise ECG are associated with an increased risk for subsequent cardiovascular events after adjustment for traditional risk factors, but the clinical implications of these findings are unclear.

Precocious virulent coronary atherosclerosis in the very young

The incidence of Myocardial Infarction (MI) in patients under the age of 30 has been rarely addressed. Moreover, it is not understood why these patients develop symptomatic Coronary Artery Disease (CAD) at such an early age. Traditional risk factor assessment has not been successful in identifying these patients before they present with MI. Retrospective, single cohort, observational study of 14,704 cardiac catheterizations performed in a community hospital between January 2006-January 2010 identified 12 cases age <30 with MI secondary to a fixed atherosclerotic lesion requiring angioplasty and stenting. The angiograms and charts were reviewed to assess the incidence and frequency of traditional risk factors such as smoking, dyslipidemia and diabetes and family history. All the patients had single vessel disease. Many of the patients were noted to have traditional CAD risk factors. 2 patients had an intervention and then months later sustained another acute MI secondary to a new culprit lesion despite aggressive risk factor modification. Evaluating patients for premature CAD by screening for traditional risk factors has not effectively identified at risk patients prior to presentation with MI. There is a role for studies evaluating new and novel risk factors and imaging modalities so that these patients can be identified prior to experiencing MI.