Improve Coronary Heart Disease Risk Prediction Research Articles

Family coronary heart disease: a call to action.

A family history of coronary heart disease (CHD) is an accepted risk factor for cardiovascular events and is independent of common CHD risk factors. Advances in the understanding of genetic influences on CHD risk provide the opportunity to apply this knowledge and improve patient care. Utility of inherited cardiovascular risk testing exists by utilizing both phenotypes and genotypes and includes improved CHD risk prediction, selection of the most appropriate treatment, prediction of outcome, and family counseling. The major impediment to widespread clinical adoption of this concept involves un-reimbursed staff time, educational needs, access to a standardized and efficient assessment mechanism, and privacy issues. The link between CHD and inheritance is indisputable and the evidence strong and consistent. For clinicians, the question is how to utilize this information, in an efficient manner, in order to improve patient care and detection of high-risk family members.

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.

Carotid Intima-Media Thickness and Presence or Absence of Plaque Improves Prediction of Coronary Heart Disease Risk: The ARIC (Atherosclerosis Risk In Communities) Study

We evaluated whether carotid intima-media thickness (CIMT) and the presence or absence of plaque improved coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). Traditional CHD risk prediction schemes need further improvement as the majority of the CHD events occur in the "low" and "intermediate" risk groups. On an ultrasound scan, CIMT and presence of plaque are associated with CHD, and therefore could potentially help improve CHD risk prediction. Risk prediction models (overall, and in men and women) considered included TRF only, TRF plus CIMT, TRF plus plaque, and TRF plus CIMT plus plaque. Model predictivity was determined by calculating the area under the receiver-operating characteristic curve (AUC) adjusted for optimism. Cox proportional hazards models were used to estimate 10-year CHD risk for each model, and the number of subjects reclassified was determined. Observed events were compared with expected events, and the net reclassification index was calculated. Of 13,145 eligible subjects (5,682 men, 7,463 women), approximately 23% were reclassified by adding CIMT plus plaque information. Overall, the CIMT plus TRF plus plaque model provided the most improvement in AUC, which increased from 0.742 (TRF only) to 0.755 (95% confidence interval for the difference in adjusted AUC: 0.008 to 0.017) in the overall sample. Similarly, the CIMT plus TRF plus plaque model had the best net reclassification index of 9.9% in the overall population. Sex-specific analyses are presented in the manuscript. Adding plaque and CIMT to TRF improves CHD risk prediction in the ARIC (Atherosclerosis Risk In Communities) study.

THE 9P21 GENETIC VARIANT IS ADDITIVE TO CAROTID INTIMA MEDIA THICKNESS AND PLAQUE IN IMPROVING CORONARY HEART DISEASE RISK PREDICTION IN WHITE PARTICIPANTS OF THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY

Objective: We evaluated whether the addition of carotid intima media thickness and plaque (CIMT-P), and a single nucleotide polymorphism on chromosome 9p21 (9p21) together improve coronary heart disease (CHD) risk prediction in the ARIC study. Methods: Ten year CHD risk was estimated using the ARIC coronary risk score (ACRS) alone and in combination with CIMT-P and 9p21 individually and together in White participants (n = 9338). Area under the receiver operating characteristic curve (AUC), model calibration, net reclassification index (NRI), eywords: arotid intima media thickness laque p21 isk prediction oronary heart disease integrated discrimination index (IDI) and number of individuals reclassified were estimated. Results: The AUC of the ACRS, ACRS + 9p21, ACRS + CIMT-P and ACRS + CIMT-P + 9p21 models were 0.748, 0.751, 0.763 and 0.766 respectively. The percentage of individuals reclassified, model calibration, NRI and IDI improved when CIMT-P and 9p21 were added to the ACRS only model (see manuscript). Conclusion: Addition of 9p21 allele information to CIMT-P minimally improves CHD risk prediction in whites in the ARIC study. © 2012 Elsevier Ireland Ltd. All rights reserved.

Higher Level of Systemic C‐Reactive Protein Is Independently Predictive of Coronary Heart Disease in Older Community‐Dwelling Adults: The Three‐City Study

To assess the association between systemic C-reactive protein (CRP) and incident coronary heart disease (CHD) in community-dwelling elderly people. A French population-based multicenter prospective cohort study. Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast. After 4 years of follow-up, a case-cohort study was designed including 1,004 subjects randomly selected from the initial cohort of 9,294 subjects free of CHD at baseline and 174 subjects who developed first CHD events during follow-up. Hazard ratios (HRs) were estimated using a Cox proportional hazard model adapted for the case-cohort design using a CRP level less than 1 mg/L as the reference category. Of the random sample, 24.3% had a CRP level less than 1.0 mg/L, 45.8% had a CRP level of 1.0 to 2.9 mg/L, and 29.9% had a CRP level of 3.0 to 10.0 mg/L. The HRs for CHD, adjusted for age, sex, and study center, were 1.69 (95% confidence interval (CI)=1.04-2.75) for CRP from 1.0 to 2.9 mg/L and 2.32 (95% CI=1.41-3.82) for CRP from 3.0 to 10.0 mg/L (P for trend <.001). After additional adjustment for smoking, body mass index, diabetes mellitus, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, statin use, and antihypertensive treatment, a baseline CRP of 3.0 to 10.0 mg/L remained associated with risk of CHD (HR=1.87, 95% CI=1.09-3.25), although CRP did not improve the discriminative ability of a predicting model based on traditional risk factors (receiver operating characteristic curves from 0.740 to 0.749). CRP is an independent CHD risk marker but does not improve CHD risk prediction in community-dwelling elderly people.

Value of genetic profiling for the prediction of coronary heart disease

Advances in high-throughput genomics facilitate the identification of novel genetic susceptibility variants for coronary heart disease (CHD). This may improve CHD risk prediction. The aim of the present simulation study was to investigate to what degree CHD risk can be predicted by testing multiple genetic variants (genetic profiling). We simulated genetic profiles for a population of 100,000 individuals with a 10-year CHD incidence of 10%. For each combination of model parameters (number of variants, genotype frequency and odds ratio [OR]), we calculated the area under the receiver operating characteristic curve (AUC) to indicate the discrimination between individuals who will and will not develop CHD. The AUC of genetic profiles could rise to 0.90 when 100 hypothetical variants with ORs of 1.5 and genotype frequencies of 50% were simulated. The AUC of a genetic profile consisting of 10 established variants, with ORs ranging from 1.13 to 1.42, was 0.59. When 2, 5, and 10 times as many identical variants would be identified, the AUCs were 0.63, 0.69, and 0.76. To obtain AUCs similar to those of conventional CHD risk predictors, a considerable number of additional common genetic variants need to be identified with preferably strong effects.

Impact of adding a single allele in the 9p21 locus to traditional risk factors on reclassification of coronary heart disease risk and implications for lipid-modifying therapy in the Atherosclerosis Risk in Communities study.

A single-nucleotide polymorphism on chromosome 9p21, rs10757274 (9p21 allele), has been shown to predict coronary heart disease (CHD) in whites. We evaluated whether adding the 9p21 allele to traditional risk factors (RFs) improved CHD risk prediction in whites from the Atherosclerosis Risk in Communities study and whether changes in risk prediction would modify lipid therapy recommendations. Whites (n=9998) in the Atherosclerosis Risk in Communities study for whom the 9p21 genotype and traditional RF information was available were included. Using Cox proportional hazards models, the Atherosclerosis Risk in Communities Cardiovascular Risk Score, which is based on traditional RFs, was determined. A total of 1349 individuals (13.5%) developed incident CHD events during a period of 14.6 years. Adding the 9p21 allele to traditional RFs was associated with a hazard ratio of incident CHD of 1.2 per allele (P<0.000003) and a significant increase in the area under the curve of the receiver operating characteristic from 0.782 to 0.786 (95% CI, 0.001, 0.007). The 9p21 allele's greatest influence to the Atherosclerosis Risk in Communities Cardiovascular Risk Score was observed in the intermediate-low (>5% to <or=10% 10-year CHD risk) and intermediate-high (>10% to <or=20% 10-year CHD risk) categories, with 12.1% and 12.6% reclassified, respectively. This may impact therapy because 90% of these reclassified individuals had low-density lipoprotein cholesterol >100 mg/dL. Adding the 9p21 allele to traditional RFs in whites in the Atherosclerosis Risk in Communities study modestly improved CHD risk prediction in the intermediate categories.

“Risky Business”

Nobody can go back and start a new beginning, but anyone can start today and make a new ending. — —Maria Robinson Although the Framingham Risk Score forms the bedrock of coronary heart disease (CHD) risk prediction, it has several limitations that have been well documented.1 The clinician is left to manage a significant proportion of patients who have “low to intermediate” estimated risk but accrue the majority of CHD events because they form the majority (≈65%) of the population. Article p 382 To address these deficiencies in the prediction of risk, several investigators have included other markers of risk such as biomarkers related to inflammation, genotypes, or imaging tests with traditional risk factors to improve CHD risk prediction. These analyses have resulted in the creation of novel risk-prediction schemes such as the Reynolds risk score, which added family history and high-sensitivity C-reactive protein (hs-CRP) to blood pressure, smoking, total and high-density lipoprotein cholesterol, and hemoglobin A1C to predict risk.2 However, whether algorithms have used biomarkers such as hs-CRP, imaging tests such as coronary calcium score or carotid intima-media thickness, or novel genotypes such as the single-nucleotide polymorphism on chromosome 9p21, the improvements in risk prediction have been modest. Other investigators have suggested that anybody who is not at very low risk should get an imaging test to further stratify risk.3 On the other hand, there have been efforts to identify the “lifetime risk” of CHD for individuals in various age groups. The concept of lifetime risk was highlighted in the National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines4 and is an important one, especially for individuals who are young to middle-aged. Traditional risk factors become manifest more often in the 4th and 5th decades of life when the estimated lifespan based on …

Abstract 5090: Impact of Adding a Single Allele in the 9p21 Locus to Traditional Risk Factors on Risk Classification for Coronary Heart Disease and Implications for Lipid-Modifying Therapy in the White Population of the Atherosclerosis Risk in Communities (ARIC) Study

Aim: A single nucleotide polymorphism on chromosome 9p21, rs10757274 (9p21 allele), has been shown to be a predictor of coronary heart disease (CHD) in whites. We evaluated if the addition of the 9p21 allele to traditional risk factors (TRF) improved CHD risk prediction in the white population of the Atherosclerosis Risk in Communities (ARIC) study, and whether changes in risk prediction will modify lipid therapy recommendation. Methods: Whites (n=10,004) in the ARIC study for whom the 9p21 genotype and TRF (age, gender, systolic blood pressure, total cholesterol, smoking, diabetes, HDL-C, and anti-hypertensive medication use) information was available were included. Using Cox proportional hazards models, the ARIC Cardiovascular Risk Score (ACRS) which is based on TRF was determined. The impact of adding the 9p21 allele to TRF with respect to the area under the curve (AUC) of a receiver operating characteristic (ROC) curve and then risk strata reclassification was determined. Results: The addition of 9p21 allele to TRF was associated with a hazard ratio (HR) of 1.25 (p&lt;0.0001) and an increase in the AUC for incident CHD from 0.776 to 0.780 (Δ= 0.004, 95% CI=0.001, 0.008). The 9p21 allele’s greatest influence to the ACRS (Table ) was observed in the intermediate (5–10% 10-year CHD risk) and intermediate-high (10 –20% 10-year CHD risk) categories with 19.3% and 16.9% reclassified, respectively, which would impact therapy, as approximately 90% of these individuals had LDL-C &gt;100 mg/dL. Table: Reclassification in the different ACRS categories after the addition of the 9p21 allele to the traditional risk factors

Abstract 4985: Are All Patients Considered “Low Risk” for Coronary Heart Disease Really Low Risk? An Analysis from the Atherosclerosis Risk in Communities (ARIC) Study

Low risk for coronary heart disease (CHD) is defined by ATP III as a 10 year risk of &lt;10%. There have been suggestions, however, that a 10 year CHD risk of 5–10% be considered as intermediate risk. The addition of carotid intima media thickness (CIMT) has been shown to improve CHD risk prediction when added to traditional risk factors (TRF) (age, gender, high density lipoprotein cholesterol, total cholesterol, diabetes, hypertension and cigarette smoking) in the ARIC study. We investigated the absolute event rates with and without the addition of CIMT to TRF in the ARIC study and determined the impact in the 0–10% risk group. Participants in the ARIC study (n=13145) without baseline CHD or stroke and with CIMT measurements available were included for this analysis. Using Cox proportional hazards models the participants were classified into various risk categories using TRF and further classified by sex specific CIMT (categorized as &lt;25 th , 25 th to 75 th and &gt;75 th percentile). The absolute event rates were then described in each group (table ). Over a mean follow up of 13.8 years, 1601 (12.2%) individuals had incident CHD events. Approximately 31% of these incident CHD events were in the 5–10% risk group which made up 28% of the study while only 16% of the incident CHD events occurred in the 0–5% risk group which made up 47% of the study population. The 5–10% group had event rates (13.7%) greater than the study average (12.2%), especially in those with thicker CIMT (&gt;75 th percentile, event rate 17%), and greater event rates than those in the 0–5% risk group (4.1%) (table ). Given the notably higher observed CHD risk in the 5–10% group (especially in those with thicker CIMT) relative to the 0–5% group, the availability of safe, low cost lipid lowering medications and low risk tests such as ultrasound that may improve risk stratification, it may be time to evaluate the low risk group more carefully for cardiovascular preventive therapies. Table. Incident CHD in the various risk groups over a mean follow up of 13.8 years in the ARIC study

The Metabolic Syndrome and 11-Year Risk of Incident Cardiovascular Disease in the Atherosclerosis Risk in Communities Study

To assess the magnitude of the association between the National Cholesterol Education Program's Third Adult Treatment Panel Report (ATP III) definition of the metabolic syndrome and cardiovascular disease (CVD). Cox regression was used to estimate the relative risk of incident coronary heart disease (CHD) and stroke among 12,089 black and white middle-aged individuals in the Atherosclerosis Risk in Communities (ARIC) study. The metabolic syndrome was present in approximately 23% of individuals without diabetes or prevalent CVD at baseline. Over an average of 11 years of follow-up, 879 incident CHD and 216 ischemic stroke events occurred. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL cholesterol exhibited the strongest associations with CHD. Men and women with the metabolic syndrome were approximately 1.5 and 2 times more likely to develop CHD than control subjects after adjustment for age, smoking, LDL cholesterol, and race/ARIC center (sex interaction P < 0.03). Similar associations were found between the metabolic syndrome and incident ischemic stroke. Comparison of receiver operating characteristic curves indicated that the metabolic syndrome did not materially improve CHD risk prediction beyond the level achieved by the Framingham Risk Score (FRS). Individuals without diabetes or CVD, but with the metabolic syndrome, were at increased risk for long-term cardiovascular outcomes, although statistical models suggested that most of that risk was accounted for by the FRS. Nevertheless, identification of individuals with the metabolic syndrome may provide opportunities to intervene earlier in the development of shared disease pathways that predispose individuals to both CVD and diabetes.