Intermediate Coronary Heart Disease Risk Research Articles

Effect of disclosing a polygenic risk score for coronary heart disease on adverse cardiovascular events: 10-year follow-up of the MI-GENES randomized clinical trial.

The MI-GENES clinical trial (NCT01936675), in which participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (FRSg, n=103), or an integrated risk score (IRSg, n=104) that additionally included a polygenic risk score (PRS), demonstrated that after 6 months, participants randomized to IRSg had higher statin initiation and lower low-density lipoprotein cholesterol (LDL-C). In a post hoc 10-year follow-up analysis of the MI-GENES trial, we investigated whether disclosure of a PRS for CHD was associated with a reduction in adverse cardiovascular events. Participants were followed from randomization beginning in October 2013 until September 2023 to ascertain adverse cardiovascular events, testing for CHD, and changes in risk factors, by blinded review of electronic health records. The primary outcome was the time from randomization to the occurrence of the first major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and non-fatal stroke. Statistical analyses were conducted using Cox proportional hazards regression and linear mixed-effects models. We followed all 203 participants who completed the MI-GENES trial, 100 in FRSg and 103 in IRSg (mean age at the end of follow-up: 68.2±5.2, 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in FRSg and 2 in IRSg (hazard ratio (HR), 0.20; 95% confidence interval (CI), 0.04 to 0.94; P=0.042). In FRSg, 47 (47%) underwent at least one test for CHD, compared to 30 (29%) in IRSg (HR, 0.51; 95% CI, 0.32 to 0.81; P=0.004). IRSg participants had a longer duration of statin therapy during the first four years post-randomization and a greater reduction in LDL-C for up to 3 years post-randomization. No significant differences between the two groups were observed for hemoglobin A1C, systolic and diastolic blood pressures, weight, and smoking cessation rate during follow-up. The disclosure of an IRS that included a PRS to individuals at intermediate risk for CHD was associated with a lower incidence of MACE after a decade of follow-up, likely due to a higher rate of initiation and longer duration of statin therapy, leading to lower LDL-C levels.

The atherosclerosis burden score.

Purpose: We carried out this study to evaluate the predictive value of atherosclerosis burden score (ABS) to predict coronary artery disease (CAD) among asymptomatic patients without known cardiovascular disease (CVD), as compared to other imaging or functional techniques, namely coronary artery calcium (CAC) score, carotid intima-media thickness (C-IMT), and ankle brachial index (ABI). Patients and methods: This prospective study included 198 asymptomatic consecutive patients referred for evaluation of their cardiovascular (CV) risk and for therapeutic advice. Traditional CV risk factors, ABS, CAC score, C-IMT, ABI and an ECG-synchronized coronary CT-angiography (CCTA) were performed for each patient. We compared the predictive values of these atherosclerosis markers to detect CAD defined as coronary stenosis ≥30% objectivated by CCTA. Results: Among the whole sample, the area under the receiver-operating characteristic curve (ROC-AUC) was significantly higher for CAC score (0.81, p=0.015) than for ABS, the reference (0.70) but these values were lower for C-IMT (0.60, p=0.16) and particularly for ABI (0.56, p=0.0015). However, among patients at intermediate risk of coronary heart disease (CHD), according to Framingham risk score (FRS), the differences between the ROC-AUC values for ABS (0.70) and CAC score (0.76, p=0.36) were less pronounced. Again, as compared to ABS, the ROC-AUC values were lower for C-IMT (0.60, p=0.21) and ABI (0.57, p=0.06). Conclusions: ABS, an ultrasonographic score based on the assessment of carotid and femoral plaque burden, predicts more accurately CAD than other non-radiation tools analyzed here, and has a similar performance to CAC in patients at intermediate CHD risk. Thus, ABS could be an appropriate non-invasive and safe method to improve the detection of high-risk patients who will benefit from a more intensive therapy for the primary prevention of CVD.

Electronic health record access by patients as an indicator of information seeking and sharing for cardiovascular health promotion in social networks: Secondary analysis of a randomized clinical trial.

We investigated electronic health record (EHR) access as an indicator of cardiovascular health promotion by patients in their social networks, by identifying individuals who viewed their coronary heart disease (CHD) risk information in the EHR and shared this information in their social networks among various spheres of influence. In a secondary analysis of the Myocardial Infarction Genes trial, Olmsted County MN residents (2013–2015; n = 203; whites, ages 45–65 years) at intermediate CHD risk were randomized to receive their conventional risk score (CRS; based on traditional risk factors) alone or also their genetic risk score (GRS; based on 28 genomic variants). We assessed self-reported and objectively quantified EHR access via a patient portal at three and six months after risk disclosure, and determined whether this differed by GRS disclosure. Data were analyzed using logistic regression and adjusted for sociodemographic characteristics, family history, and baseline CRS/GRS. Self-reported EHR access to view CHD risk information was associated with a high frequency of objectively quantified EHR access (71(10) versus 37(5) logins; P = 0.0025) and a high likelihood of encouraging others to be screened for their CHD risk (OR 2.936, CI 1.443–5.973, P = 0.0030), compared to the absence of self-reported EHR access to view CHD risk information. We thereby used EHR access trends to identify individuals who may function as disseminators of CHD risk information in social networks, compared to individuals on the periphery of their social networks who did not exhibit this behavior. Partnering with such individuals could amplify CHD health promotion.Clinical Trial Registration: Myocardial Infarction Genes (MI-GENES) Study, NCT01936675, https://clinicaltrials.gov/ct2/show/NCT01936675.

Effect of Disclosing Genetic Risk for Coronary Heart Disease on Information Seeking and Sharing: The MI-GENES Study (Myocardial Infarction Genes).

Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. We hypothesized that disclosing genetic risk for CHD to individuals influences information seeking and sharing. The MI-GENES study (Myocardial Infarction Genes) randomized participants (n=203) aged 45 to 65 years who were at intermediate CHD risk based on conventional risk factors and not on statins to receive their conventional risk score alone or also a genetic risk score based on 28 variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys assessing information seeking were completed before and after risk disclosure. Information sharing was assessed post-disclosure. Six-month post-disclosure, genetic risk score participants were more likely than conventional risk score participants to visit a website to learn about CHD (odds ratio [OR], 4.88 [confidence interval (CI), 1.55-19.13]; P=0.01), use the internet for information about how genetic factors affect CHD risk (OR, 2.11 [CI, 1.03-4.47]; P=0.04), access their CHD risk via a patient portal (OR, 2.99 [CI, 1.35-7.04]; P=0.01), and discuss their CHD risk with others (OR, 3.13 [CI, 1.41-7.47]; P=0.01), particularly their siblings (OR, 1.92 [CI, 1.06-3.51]; P=0.03), extended family (OR, 3.8 [CI, 1.37-12.38]; P=0.01), coworkers (OR, 2.42 [CI, 1.09-5.76]; P=0.03), and primary care provider (PCP; OR, 2.00 [CI, 1.08-3.75]; P=0.03). Disclosure of a genetic risk score for CHD increased information seeking and sharing. URL: https://clinicaltrials.gov/. Unique identifier: NCT01936675.

Shared decision-making following disclosure of coronary heart disease genetic risk: results from a randomized clinical trial

Whether disclosure of genetic risk for coronary heart disease (CHD) influences shared decision-making (SDM) regarding use of statins to reduce CHD risk is unknown. We randomized 207 patients, age 45–65...

Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial).

Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Participants (n=203, 45-65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ((+)GRS). Participants in the (+)GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or (+)GRS (n=103). At the end of the study period, the (+)GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the (+)GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted. Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.

Coronary artery calcium score and N-terminal pro-B-type natriuretic peptide as potential gatekeepers for myocardial perfusion imaging.

Myocardial perfusion imaging (MPI) holds an important place as non-invasive risk assessment in patients with intermediate risk of coronary heart disease (CHD). However, as much as 60-70% of MPI scans are normal. This study evaluates the role of coronary artery calcium scoring (CAC score) and NT-proBNP as potential gatekeepers for MPI. Patients with intermediate risk of CHD referred for standard MPI were included. CAC score and NT-proBNP were both assessed at the day of the stress study. Sensitivity, specificity and NPV for prediction of abnormal MPI scans were calculated for CAC, NT-proBNP and the combination hereof. A total of 190 patients were included (mean age 61±12years, 55% female) of whom 24% had known CHD. In all 30% of the scans were abnormal. CAC score achieved the highest AUC regardless of whether patients with known CHD were included or not [AUC 0·75 95% CI (0·66-0·84) and AUC 0·79 (0·68-0·91)]. As a singular variable, CAC score was the most potent predictor with a sensitivity of 85%, specificity of 39% and NPV 88%. The combination of CAC score<10 and NT-proBNP>26 reached a sensitivity of 98% and NPV 94%, where 8% of scans tentatively could be avoided. In patients referred for MPI with intermediate risk for CHD, a combination of CAC score and NT-proBNP could be used to identify a group of patients where MPI could be averted with a high degree of diagnostic safety.

Abstract 16508: Effect of Disclosure of Genetic Risk for Coronary Heart Disease on Information Seeking and Information Sharing in a Randomized Clinical Trial (from the MI-GENES Investigators)

Background: Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. Methods: The myocardial infarction genes (MI-GENES) trial randomized participants aged 45-65 years who were at intermediate risk for CHD based on conventional risk factors and not on statins, to receive their conventional risk score (CRS) or their CRS plus a genetic risk score (GRS) based on 28 susceptibility variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys to assess information seeking (including internet use and accessing electronic health records (EHR)) were completed before and three and six months after risk disclosure. Information sharing parameters were assessed after risk disclosure. We assessed whether these behaviors differed by GRS disclosure, or by high (≥1.1) or low (&lt;1.1) GRS. Adjustments were made for age, sex, family history of CHD, baseline CRS and GRS, and education. Results were reported as the mean difference (and standard error) in the score for each survey response between the GRS and CRS participants, with significance determined by regression analysis. Results: GRS participants accessed their EHR to obtain information related to their CHD risk more than CRS participants (0.14 ± 0.06, p=0.03). Overall internet use (0.61 ± 0.23, p=0.01), as well as internet use to seek information about heart disease (0.14 ± 0.06, p=0.02) and how genetic factors affect risk of having a heart attack (0.23 ± 0.07, p=0.002), was significantly higher in the GRS participants. GRS participants shared information about heart attack risk with others (0.35 ± 0.13, p=0.007), particularly family members (0.1 ± 0.04, p=0.02), (V4: 0.10 ± 0.05, p=0.05), and their primary care provider (V4: 0.15 ± 0.07, p=0.03) more than CRS participants. Internet use, EHR access, and information sharing did not differ significantly between the high and low GRS groups. Conclusions: Disclosure of GRS for CHD resulted in greater information seeking (including internet use and EHR access) and information sharing by study participants. Disclosure of genetic risk for CHD may help advance patient engagement in precision medicine.

Association between Red Blood Cell Distribution Width and Coronary Artery Calcification in Patients Undergoing 64-Multidetector Computed Tomography.

Background and ObjectivesThe red blood cell distribution width (RDW) has been found to be associated with cardiovascular morbidity and mortality. The objective of this study was to determine whether the RDW measures are associated with the coronary artery calcification score (CACS) in patients who did not present with obvious coronary heart disease (CHD).Subjects and MethodsA total of 527 consecutive patients with a low to intermediate risk for CHD but without obvious disease were enrolled in this study. The study subjects underwent coronary computerized tomography angiography and CACS was calculated. The patients were divided into two groups based on CACS: Group I (CACS≤100) and Group II (CACS>100). The two groups were compared in terms of classic CHD risk factors and haematological parameters, particularly the RDW.ResultsGroup I patients were younger than Group II patients. The Framingham risk score (FRS) in patients of Group II was significantly higher than that in patients of Group I. Group II patients had significantly elevated levels of haemoglobin, RDW, neutrophil count, and neutrophil/lymphocyte ratio compared with Group I patients. CACS was correlated with age, RDW, and ejection fraction. In the multivariate analysis, age, RDW, and FRS were independent predictors of CACS. Using the receiver-operating characteristic curve analysis, a RDW value of 13.05% was identified as the best cut-off for predicting the severity of CACS (>100) (area under the curve=0.706).ConclusionWe found that the RDW is an independent predictor of the CACS, suggesting that it might be a useful marker for predicting CAD.

Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease.

Genome-wide association studies have identified several genetic variants associated with coronary heart disease (CHD). The aim of this study was to evaluate the genetic risk discrimination and reclassification and apply the results for a 2-stage population risk screening strategy for CHD. We genotyped 28 genetic variants in 24 124 participants in 4 Finnish population-based, prospective cohorts (recruitment years 1992-2002). We constructed a multilocus genetic risk score and evaluated its association with incident cardiovascular disease events. During the median follow-up time of 12 years (interquartile range 8.75-15.25 years), we observed 1093 CHD, 1552 cardiovascular disease, and 731 acute coronary syndrome events. Adding genetic information to conventional risk factors and family history improved risk discrimination of CHD (C-index 0.856 versus 0.851; P=0.0002) and other end points (cardiovascular disease: C-index 0.840 versus 0.837, P=0.0004; acute coronary syndrome: C-index 0.859 versus 0.855, P=0.001). In a standard population of 100 000 individuals, additional genetic screening of subjects at intermediate risk for CHD would reclassify 2144 subjects (12%) into high-risk category. Statin allocation for these subjects is estimated to prevent 135 CHD cases over 14 years. Similar results were obtained by external validation, where the effects were estimated from a training data set and applied for a test data set. Genetic risk score improves risk prediction of CHD and helps to identify individuals at high risk for the first CHD event. Genetic screening for individuals at intermediate cardiovascular risk could help to prevent future cases through better targeting of statins.

Markers for Prediction of Cardiovascular Disease Risk

To the Editor: The article by Dr Yeboah and colleagues compared the ability of several risk markers to improve prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) among individuals at intermediate risk. The authors reported that coronary artery calcium (CAC) provided superior reclassification compared with other risk markers and recommended CAC as a tool for refining cardiovascular risk prediction in individuals at intermediate risk. While the added predictive ability of CAC in CHD risk prediction was substantial and confirmed previous findings, we believe that supporting CAC as a candidate for CVD screening based on the results is less grounded. While it is straightforward to define an intermediaterisk group for CHD, this is not the case for CVD because accepted thresholds are lacking. In the study by Yeboah et al, the authors included persons at intermediate risk for CHD and therefore the results might not necessarily apply to persons at intermediate risk for CVD. While CAC has been shown to accurately predict CHD in different populations, CAC has not been proven to be a useful predictor for stroke. In the study by Yeboah et al, addition of CAC to the Framingham risk score provided overall net reclassification improvement of 0.66 for CHD and 0.47 for CVD risk prediction. The percentage net correct reclassification in the group without events hardly changed after adding a non–CAC-related outcome such as stroke (40.4% for CHD and 36.0% for CVD). However, the percentage net correct reclassification for those with events, which reflects the ability to identify persons who will benefit from intensive treatment, dropped from 25.5% for CHD and 10.6% for CVD. The percentage net correct reclassification for persons with CHD events of 25.5% in the current study and 24.0% previously reported imply that adding CAC to risk prediction models moves a substantial proportion of persons initially at intermediate risk to the high-risk group, in which they qualify for more aggressive treatment. This supports the incorporation of CAC in CHD risk assessment. However, whether 10.6% net correct reclassification of persons with CVD events provided by CAC is sufficiently large to warrant recommending CAC as a screening tool for CVD is doubtful. The general trend in developing new guidelines on cardiovascular risk prevention is moving toward focusing on broader CVD risk rather than on CHD risk only. However, before considering new markers for CVD risk prediction, all components of this broad outcome should be considered and limitations for stroke risk prediction should be recognized.

Comparative Effectiveness and Cost-Effectiveness of Computed Tomography Screening for Coronary Artery Calcium in Asymptomatic Individuals

The aim of this study was to assess the (cost-) effectiveness of screening asymptomatic individuals at intermediate risk of coronary heart disease (CHD) for coronary artery calcium with computed tomography (CT). Coronary artery calcium on CT improves prediction of CHD. A Markov model was developed on the basis of the Rotterdam Study. Four strategies were evaluated: 1) current practice; 2) current prevention guidelines for cardiovascular disease; 3) CT screening for coronary calcium; and 4) statin therapy for all individuals. Asymptomatic individuals at intermediate risk of CHD were simulated over their remaining lifetime. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios were calculated. In men, CT screening was more effective and more costly than the other 3 strategies (CT vs. current practice: +0.13 QALY [95% confidence interval (CI): 0.01 to 0.26], +$4,676 [95% CI: $3,126 to $6,339]; CT vs. statin therapy: +0.04 QALY [95% CI: -0.02 to 0.13], +$1,951 [95% CI: $1,170 to $2,754]; and CT vs. current guidelines: +0.02 QALY [95% CI: -0.04 to 0.09], +$44 [95% CI: -$441 to $486]). The incremental cost-effectiveness ratio of CT calcium screening was $48,800/QALY gained. In women, CT screening was more effective and more costly than current practice (+0.13 QALY [95% CI: 0.02 to 0.28], +$4,663 [95% CI: $3,120 to $6,277]) and statin therapy (+0.03 QALY [95% CI: -0.03 to 0.12], +$2,273 [95% CI: $1,475 to $3,109]). However, implementing current guidelines was more effective compared with CT screening (+0.02 QALY [95% CI: -0.03 to 0.07]), only a little more expensive (+$297 [95% CI: -$8 to $633]), and had a lower cost per additional QALY ($33,072/QALY vs. $35,869/QALY). Sensitivity analysis demonstrated robustness of results in women but considerable uncertainty in men. Screening for coronary artery calcium with CT in individuals at intermediate risk of CHD is probably cost-effective in men but is unlikely to be cost-effective in women.

Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study

ObjectiveThe value of a family history for coronary heart disease (CHD) in addition to established cardiovascular risk factors in predicting an individual's risk of CHD is unclear. In the European...

Coronary Calcium Score Improves Classification of Coronary Heart Disease Risk in the Elderly: The Rotterdam Study

The purpose of this study was to examine the effect of coronary artery calcium (CAC) on the classification of 10-year hard coronary heart disease (CHD) risk and to empirically derive cut-off values of the calcium score for a general population of elderly patients.Although CAC scoring has been found to improve CHD risk prediction, there are limited data on its impact in clinical practice.The study comprised 2,028 asymptomatic participants (age 69.6 ± 6.2 years) from the Rotterdam Study. During a median follow-up of 9.2 years, 135 hard coronary events occurred. Persons were classified into low (<10%), intermediate (10% to 20%), and high (>20%) 10-year coronary risk categories based on a Framingham refitted risk model. In a second step, the model was extended by CAC, and reclassification percentages were calculated. Cutoff values of CAC for persons in the intermediate-risk category were empirically derived based on 10-year hard CHD risk.Reclassification by means of CAC scoring was most substantial in persons initially classified as intermediate risk. In this group, 52% of men and women were reclassified, all into more accurate risk categories. CAC values above 615 or below 50 Agatston units were found appropriate to reclassify persons into high or low risk, respectively.In a general population of elderly patients at intermediate CHD risk, CAC scoring is a powerful method to reclassify persons into more appropriate risk categories. Empirically derived CAC cutoff values at which persons at intermediate risk reclassified to either high or low risk were 615 and 50 Agatston units, respectively.

The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population

BackgroundEpidemiological studies have shown a J- or U-shaped relation between alcohol and type 2 diabetes and coronary heart disease (CHD). The underlying mechanisms are not clear. The aim was to examine the association between alcohol intake and diabetes and intermediate CHD risk factors in relation to selected ADH and ALDH gene variants.Methodology/Principal FindingsCross-sectional study including 6,405 Northern European men and women aged 30–60 years from the general population of Copenhagen, Denmark. Data were collected with self-administered questionnaires, a physical examination, a 2 hour oral glucose tolerance test, and various blood tests. J shaped associations were observed between alcohol and diabetes, metabolic syndrome (MS), systolic and diastolic blood pressure, triglyceride, total cholesterol, and total homocysteine. Positive associations were observed with insulin sensitivity and HDL cholesterol, and a negative association with insulin release. Only a few of the selected ADH and ALDH gene variants was observed to have an effect. The ADH1c (rs1693482) fast metabolizing CC genotype was associated with an increased risk of impaired glucose tolerance (IGT)/diabetes compared to the CT and TT genotypes. Significant interactions were observed between alcohol and ADH1b (rs1229984) with respect to LDL and between alcohol and ALDH2 (rs886205) with respect to IGT/diabetes.Conclusions/SignificanceThe selected ADH and ALDH gene variants had only minor effects, and did not seem to markedly modify the health effects of alcohol drinking. The observed statistical significant associations would not be significant, if corrected for multiple testing.

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.

The SHAPE Paradigm

Atherosclerosis is a chronic immunoinflammatory disease trigerred by lipoprotein retention in the subendothelium and produces its most serious manifestations by triggering arterial thrombosis when the plaque ruptures or erodes.1 Atherothrombotic cardiovascular disease remains the leading cause of death in the West and is achieving similar dubious distinction in developing countries.2 Atherosclerosis begins at a young age, but it remains clinically silent for a long time and the majority of clinical manifestations occur later in life. Despite considerable progress, regrettably 50% of life-threatening acute cardiovascular events occur in previously asymptomatic individuals. Identifying individuals at risk for future cardiovascular events affords an opportunity for risk reduction and thus remains a major imperative for healthcare professionals. In 2006 the SHAPE (Society for Heart Attack Prevention and Education) Task Force introduced an algorithm incorporating noninvasive screening for subclinical atherosclerosis to augment risk factor–based risk stratification in asymptomatic subjects between the ages of 45 to 75 in men and 55 to 75 in women, excluding those at very low risk or at high risk.3 In June 2009, the Texas Governor Rick Perry signed off on the Texas Heart Attack Prevention Bill introduced by Rep Rene Oliveira, mandating health-benefit plans to cover noninvasive screening for subclinical atherosclerosis. This bill grew out of the 2006 SHAPE Task Force guidelines and became effective September 1, 2009; an earlier version of the bill had been rejected in 2007. This generated a mixed reaction from healthcare professionals and others, much of which played out in the media. The critics argued that such an action is inappropriate because: (1) the SHAPE guidelines were created by an ad hoc group and had not been explicitly endorsed by the American College of Cardiology (ACC) or the American Heart Association (AHA), and (2) SHAPE guidelines are not based on randomized clinical …

Eligibility of Individuals With Subclinical Coronary Artery Calcium and Intermediate Coronary Heart Disease Risk for Reclassification (from the Framingham Heart Study)

Coronary artery calcium (CAC) predicts risk for coronary heart disease (CHD) events and perhaps CAC testing may further stratify risk in individuals at intermediate CHD risk. We sought to determine the percentage of participants at intermediate CHD risk who could potentially be reclassified as having a high CHD risk based on the presence of a high CAC score and the prevalence, treatment, and control of CHD risk factors in this group. Framingham Heart Study Offspring and Third Generation cohort participants underwent multidetector computed tomography (n = 3,529, mean age 51 years, 48% women). High CAC was defined as >or=90th age- and gender-specific percentiles based on a healthy reference group or by an absolute modified Agatston score of 100 HU. Prevalence of CHD risk factors (hypertension, hypercholesterolemia, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, smoking, and obesity), their treatment, and control was compared between nondiabetic participants with and without high CAC. Of the 595 participants at intermediate CHD risk, 22% had CAC >or=90th percentile and 39% had CAC >or=100 and could be eligible for reclassification as having a high CHD risk based on the presence of a high CAC score. There were no statistically significant differences in prevalence, treatment, and control of risk factors between those with and without high CAC. In conclusion, prevalence of CHD risk factors did not differ between intermediate-risk participants with and without high CAC. Approximately 25% of intermediate-risk individuals have high CAC scores and may be eligible for reclassification into a higher-risk category.

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.

Prediction of Intermittent Claudication, Ischemic Stroke, and Other Cardiovascular Disease by Detection of Abdominal Aortic Calcific Deposits by Plain Lumbar Radiographs

There has been little attention to vascular calcium testing for generalized assessment of cardiovascular disease (CVD) outcomes, such as intermittent claudication (IC) and ischemic stroke (IS). We hypothesize that aortic calcium is an important predictor of CVD outcomes. Lumbar x-rays were obtained in 848 men and 1,301 women (mean ages 59.7 and 60.1 years, respectively) from the original cohort of the Framingham Heart Study. Abdominal aortic calcium (AAC) deposits were graded using a previously validated scale. Participants were categorized according to a 10-year Framingham coronary heart disease (CHD) risk score. Multivariable Cox proportional hazards analyses were performed to relate AAC to CVD outcomes. There were 199 IC events, 201 IS events, 702 CHD events, and 1,121 CVD events during 32 years of follow-up. Multivariable adjusted hazard ratios for the third versus first AAC tertile in the combined cohort were 1.68 (95% confidence interval [CI] 1.12 to 2.50) for IC, 1.73 (95% CI 1.12 to 2.65) for IS, 1.59 (95% CI 1.26 to 2.00) for CHD, and 1.64 (95% CI 1.37 to 1.97) for CVD. Hazard ratios for IC and IS were similar in magnitude to those for CHD and CVD. A high AAC score was associated with significantly higher incidence of events in subjects at intermediate Framingham CHD risk for all end points. Risk prediction based on cardiovascular risk factors improved for most outcomes when AAC was added. In conclusion, there was a graded, increasing, and independent association of AAC with incident IC and IS, similar in magnitude to risks predicted for CHD and CVD. AAC appears to be useful for risk stratification in patients at intermediate CHD risk.