Hard Coronary Heart Disease Events Research Articles

Lipoprotein (a) is associated with poor long-term prognosis in patients aged 80 years and older with acute coronary syndrome

Lipoprotein(a) has been suggested as an independent risk factor for cardiovascular events in patients with coronary heart disease (CHD). This study aimed to investigate the association of lipoprotein(a) with long-term poor prognosis following acute coronary syndromes (ACS) in advanced-age patients. We enrolled 536 patients aged ≥80 years hospitalized for ACS and plasma lipoprotein(a) concentrations were measured at admission. The primary outcomes were hard CHD events (a composite of fatal or non-fatal myocardial infarction, and CHD death). The secondary outcomes included major adverse cardiovascular events (MACEs), all-cause death and cardiac death. During a median 66-month follow-up, 89 hard CHD events occurred. The optimal cutoff points of lipoprotein(a) levels were obtained from ROC curve analyses. Kaplan-Meier curves showed a significantly higher cumulative incidence of hard CHD events, MACEs, all-cause death and cardiac death in high lipoprotein(a) group than that in low lipoprotein(a) group. Multivariate Cox proportional hazards analyses revealed that elevated lipoprotein(a) levels were independently associated with an increased risk of hard CHD events [hazard ratio (HR): 1.714, 95% confidence interval (95%CI): 1.114-2.638], MACEs (HR 1.354, 95%CI: 1.024-1.790), all-cause death (HR 1.804, 95%CI: 1.286-2.532) and cardiac death (HR 1.891, 95%CI: 1.112-3.217). Furthermore, adding lipoprotein(a) to the prognostic model for hard CHD events improved the C-statistic value (P < 0.05). Elevated lipoprotein(a) levels were associated with an increased risk of hard CHD events, MACEs, all-cause death and cardiac death in the advanced-age patients with ACS, which indicated that routine screening for lipoprotein(a) might aid prognosis and risk assessment.

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

Performance of the Framingham coronary heart disease risk score for predicting 10-year cardiac risk in adult United Arab Emirates nationals without diabetes: a retrospective cohort study

BackgroundPrimary prevention guidelines recommend the use of the Framingham risk score (FRS) to estimate the 10-year coronary heart disease (CHD) risk in patients without diabetes for statin eligibility. However, the FRS model has never been validated in an Arab population. Therefore, this study aimed to examine the clinical performance of the FRS model for predicting 10-year CHD risk in adult United Arab Emirates (UAE) nationals without diabetes.MethodsThis 10-year retrospective cohort study included patients from the primary care clinics and outpatient specialty departments of a large tertiary care hospital in Al-Ain, UAE. They were aged 30–79 without a baseline history of cardiovascular disease and diabetes. The FRS for each subject was calculated. Follow-up data on hard CHD (hCHD) events (myocardial infarction or coronary death) for each participant were collected from the baseline visit in 2008 until December 31, 2019. The area under the time-dependent receiver operating characteristic (ROC) curve (AUROC) was used to assess the FRS model discrimination. Calibration was measured by using the Hosmer-Lemeshow χ2 test and the calibration curve. The optimal cutoff-point for hCHD risk prediction was determined by ROC curve analysis.ResultsA total of 554 participants were included. The mean age was 48.0 ± 12.8 years and 45% were men. The mean predicted FRS of the study cohort was 5.2% and approximately 7% were classified as high-risk (≥ 20% threshold) by the FRS model. During a median follow-up of 10.2 years (interquartile range, 7.8–11.0 years), 26 hCHD events occurred. The FRS model displayed reasonably good discrimination (time-dependent AUROC value: 0.83) and calibration in predicting hCHD (Hosmer-Lemeshow χ2 statistic 11.2, P = 0.191). Applying the 20% high-risk threshold, the FRS model had a sensitivity of only 37% in identifying patients at high-risk for an hCHD event over 10 years. While a 7.5% optimal cutoff-point improved the sensitivity to 74%.ConclusionsThe FRS can be used in the prediction of coronary risk among UAE nationals without diabetes, however, the recommended hCHD risk threshold for statin eligibility may be too high. Lowering the cutoff-point to 7.5% could improve the identification of patients for preventive treatment.

Left Ventricular Mass at MRI and Long-term Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background Few data exist on the long-term risk prediction of elevated left ventricular (LV) mass quantified by MRI for cardiovascular (CV) events in a contemporary, ethnically diverse cohort. Purpose To assess the long-term impact of elevated LV mass on CV events in a prospective cohort study of a multiethnic population in relationship to risk factors and coronary artery calcium (CAC) score. Materials and Methods The Multi-Ethnic Study of Atherosclerosis, or MESA (ClinicalTrials.gov: NCT00005487), is an ongoing prospective multicenter population-based study in the United States. A total of 6814 participants (age range, 45-84 years) free of clinical CV disease at baseline were enrolled between 2000 and 2002. In 4988 participants (2613 [52.4%] women; mean age, 62 years ± 10.1 [standard deviation]) followed over 15 years for CV events, LV mass was derived from cardiac MRI at baseline enrollment by using semiautomated software at a central core laboratory. Cox proportional hazard models, Kaplan-Meier curves, and z scores were applied to assess the impact of LV hypertrophy. Results A total of 290 participants had hard coronary heart disease (CHD) events (207 myocardial infarctions [MIs], 95 CHD deaths), 57 had other CV disease-related deaths, and 215 had heart failure (HF). LV hypertrophy was an independent predictor of hard CHD events (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.9, 3.8), MI (HR: 2.8; 95% CI: 1.8, 4.0), CHD death (HR: 4.3; 95% CI: 2.5, 7.3), other CV death (HR: 7.5; 95% CI: 4.2, 13.5), and HF (HR: 5.4; 95% CI: 3.8, 7.5) (P < .001 for all end points). LV hypertrophy was a stronger predictor than CAC for CHD death, other CV death, and HF (z scores: 5.4 vs 3.4, 6.8 vs 2.4, and 9.7 vs 3.2 for LV hypertrophy vs CAC, respectively). Kaplan-Meier analysis demonstrated an increased risk of CV events in participants with LV hypertrophy, particularly after 5 years. Conclusion Elevated left ventricular mass was strongly associated with hard coronary heart disease events, other cardiovascular death, and heart failure over 15 years of follow-up, independent of traditional risk factors and coronary artery calcium score. © RSNA, 2019 See also the editorial by Hanneman in this issue.

Association Between Self-rated Health, Coronary Artery Calcium Scores, and Atherosclerotic Cardiovascular Disease Risk

The interplay of self-rated health (SRH), coronary artery calcium (CAC) scores, and cardiovascular risk is poorly described. To assess the degree of correlation between SRH and CAC, to determine whether these measures are complementary for risk prediction, and to assess the incremental value of the addition of SRH to established risk tools. The Multi-Ethnic Study of Atherosclerosis (MESA) is a large population-based prospective cohort study of adults aged 45 to 84 years who were recruited from 6 US communities. A total of 6764 participants without baseline cardiovascular disease (CVD) were included in the analysis. Data were collected from July 2000 through August 2002. Follow-up was completed by December 2013, and data were analyzed from October 2018 to December 2018. The EVGGFP (excellent, very good, good, fair, and poor) self-assessment of overall health (assessed before the baseline study examination) and CAC score. The EVGGFP rating was categorized as poor/fair, good, very good, or excellent. Hard coronary heart disease (CHD) events, hard CVD events, and all-cause mortality during a median follow-up of 13.2 years (interquartile range, 12.7-13.7 years). Among the study population of 6764 participants, the mean (SD) age was 62.1 (10.2) years, and 52.9% were women. The EVGGFP rating was strongly associated with age, sex, race/ethnicity, educational and income levels, healthy diet and physical activity, and cardiovascular risk factors. Despite encapsulating many risk variables, no correlation (r = -0.007; P = .57) or association between EVGGFP and the presence (χ2 = 0.84; P = .84) or severity (χ2 = 4.64; P = .86) of CAC was found. During follow-up, 1161 deaths, 637 hard CVD events, and 405 hard CHD events were recorded. In models adjusted for age, sex, race/ethnicity, and CAC, participants who reported excellent health had a 45% lower risk of CVD (hazard ratio [HR], 0.55; 95% CI, 0.39-0.77) and a 42% lower risk of CHD (HR, 0.58; 95% CI, 0.37-0.90) compared with those who reported poor/fair health. Participants in the excellent SRH category who had any CAC had markedly elevated risk of hard CHD (HR, 6.19; 95% CI, 2.1-18.3) and CVD (HR, 6.50; 95% CI, 2.7-15.6) events compared with those with a CAC score of 0. The addition of the EVGGFP rating to CAC improved the area under the curve (C statistic) for CHD events (0.725 vs 0.734; P = .007), CVD events (0.693 vs 0.706; P < .001), and all-cause mortality (0.685 vs 0.707; P < .001). However, the addition of the EVGGFP rating to the combination of CAC and atherosclerotic CVD risk score did not significantly improve C statistics for CHD events (0.751 vs 0.753; P = .39), CVD events (0.739 vs 0.741; P = .18), or all-cause mortality (0.779 vs 0.781; P = .13). Although SRH and CAC integrate many risk variables, this study suggests that they are poorly correlated and have complementary predictive utility. A perception of excellent health does not obviate the need for definitive assessment of CVD risk, whereas fair/poor perceived health may serve as a risk enhancer, arguing for advanced risk assessment in selected clinical scenarios.

Progression of CAC Score and Risk of Incident CVD

The authors sought to determine the relative contributions of baseline coronary artery calcification (CAC), follow-up CAC, and CAC progression on incident cardiovascular disease (CVD). Repeat CAC scanning has been proposed as a method to track progression of total atherosclerotic burden. However, whether CAC progression is a useful predictor of future CVD events remains unclear. This was a prospective observational study of 5,933 participants free of CVD who underwent 2 examinations, including CAC scores, and subsequent CVD event assessment. CAC progression was calculated using the square root method. The primary outcome was total CVD events (CVD death, nonfatal myocardial infarction, nonfatal atherosclerotic stroke, coronary artery bypass surgery, percutaneous coronary intervention). Secondary outcomes included hard CVD events, total coronary heart disease (CHD) events, and hard CHD events. CAC was detected at baseline in 2,870 individuals (48%). The average time between scans was 3.5±2.0 years. After their second scan, 161 individuals experienced a total CVD event during a mean follow-up of7.3 years. CAC progression was significantly associated with total CVD events (hazard ratio: 1.14, 95% confidenceinterval: 1.01 to 1.30 per interquartile range; p= 0.042) in the model including baseline CAC, but thecontribution of CAC progression was small relative to baseline CAC (chi-square 4.16 vs. 65.92). Furthermore,CAC progression was not associated with total CVD events in the model including follow-up CACinstead of baseline CAC (hazard ratio: 1.05, 95% confidence interval: 0.92 to 1.21; p= 0.475). A model thatincluded follow-up CAC alone performed as well as the model that included baseline CAC and CAC progression. Although CAC progression was independently, but modestly, associated with CVD outcomes, this relationship was no longer significant when including follow-up CAC in the model. These findings imply that if serial CAC scanning is performed, the latest scan should be used for risk assessment, and in this context, CAC progression provides no additional prognostic information.

Nonlinear relation between pulse pressure and coronary heart disease in patients with type 2 diabetes or hypertension.

Wide pulse pressure (PP) is an independent predictor of coronary heart disease (CHD). However, the linearity of the relation between PP and CHD was not examined before. We aimed to examine this relation in patients with type 2 diabetes and/or hypertension. A total of 3120 patients (including 2607 with diabetes and 1586 with hypertension) were followed for 7.8 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between PP and incident CHD. Restricted cubic splines were used to investigate nonlinear relations. Four spline covariates were defined between 30, 40, 50, 60, and 70 mmHg. The null-hypothesis of the linearity of the relation between PP and CHD was rejected (P value = 0.004). The second, third, and fourth spline covariates were significant (P value = 0.02, P value = 0.02 and P value = 0.01, respectively), supporting a nonlinear relation in corresponding PP intervals. Patients with PP less than 45 mmHg and PP more than 55 mmHg had increased risk of future CHD event, compared with those with PP between 45 and 55 mmHg [hazard ratio (HR) = 1.33 (1.00-1.77) and HR = 1.67 (1.23-2.27), respectively]. This remained significant after controlling for systolic, diastolic, or mean arterial pressures in wide PP group. However, adjustment for traditional cardiovascular risk factors (especially age) attenuated the relation in those with wide PP. The relation between PP and CHD is nonlinear in patients with type 2 diabetes and hypertension. Both narrow and wide PPs increase risk of future hard CHD events. The association between wide PP and CHD is independent from SBP, DBP, or mean arterial pressure.

Contribution of vitamin D deficiency to the risk of coronary heart disease in subjects with essential hypertension

Vitamin D deficiency is proposed as a risk factor for coronary heart disease (CHD). An inverse relation was observed between serum 25-Hydroxy-Vitamin-D level and incidence of hypertension. This study aimed to evaluate the predictive value of serum 25-Hydroxy-Vitamin-D in improvement of CHD risk-stratification in patients with hypertension. In this cohort, we followed 1586 patients with essential hypertension (1078 diabetic and 508 non-diabetic) for 8.5 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between 25-Hydroxy-Vitamin-D quartiles and incident CHD. 25-Hydroxy-Vitamin-D was also added to the Framingham Risk Score (FRS) and Net-Reclassification-Improvement (NRI) and Integrated-Discriminant-Improvement (IDI) were used to examine improved reclassification. During follow-up, 176 events were recorded. Patients in the lowest quartile of 25-Hydroxy-Vitamin-D experienced the most number of hard CHD events. A significant linear trend was observed in hazard ratios (HR) of incident hard CHD events in 25-Hydroxy-Vitamin-D quartiles which remained significant after multiple adjustments for conventional CHD risk-factors (HRs in full-adjusted model: 2.87 [1.76-4.70] for 1st quartile, 2.31 [1.39-3.83] for 2nd quartile and 1.87 [1.15-3.03] for 3rd quartile, compared with the highest quartile; p-for-trend<0.001). Addition of 25-Hydroxy-Vitamin-D to FRS could improve CHD risk-estimation (relative-IDI = 15%, p-value<0.001). Addition of 25-Hydroxy-Vitamin-D to FRS successfully reclassified 33% [18-49] of patients with hypertension among CHD risk groups (p-value<0.001). We observed that serum 25-Hydroxy-Vitamin-D is independently associated with future hard CHD events and improves its prediction in patients with essential hypertension. Addition of serum 25-Hydroxy-Vitamin-D to CHD risk-estimation models may have additive values.

Implications of Coronary Artery Calcium Testing Among Statin Candidates According to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis)

The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for statin therapy. This study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not. MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment. We excluded 1,100 participants (16%) on lipid-lowering medication, 87 (1.3%) without low-density lipoprotein levels, 26 (0.4%) with missing risk factors for calculation of 10-year risk of ASCVD, 633 (9%) >75 years of age, and 209 (3%) with low-density lipoprotein <70 mg/dl from the analysis. The study population consisted of 4,758 participants (age 59 ± 9 years; 47% males). A total of 247 (5.2%) ASCVD and 155 (3.3%) hard coronary heart disease events occurred over a median (interquartile range) follow-up of 10.3 (9.7 to 10.8) years. The new ACC/AHA guidelines recommended 2,377 (50%) MESA participants for moderate- to high-intensity statins; the majority (77%) was eligible because of a 10-year estimated ASCVD risk ≥7.5%. Of those recommended statins, 41% had CAC = 0 and had 5.2 ASCVD events/1,000 person-years. Among 589 participants (12%) considered for moderate-intensity statin, 338 (57%) had a CAC = 0, with an ASCVD event rate of 1.5 per 1,000 person-years. Of participants eligible (recommended or considered) for statins, 44% (1,316 of 2,966) had CAC = 0 at baseline and an observed 10-year ASCVD event rate of 4.2 per 1,000 person-years. Significant ASCVD risk heterogeneity exists among those eligible for statins according to the new guidelines. The absence of CAC reclassifies approximately one-half of candidates as not eligible for statin therapy.

Cigarette smoking and cardiovascular events: role of inflammation and subclinical atherosclerosis from the MultiEthnic Study of Atherosclerosis.

To examine the contemporary effect of smoking in a multiethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking. We studied 6814 participants free of cardiovascular disease and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox regression was used to estimate the association between smoking parameters and all-cause cardiovascular disease, all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C-reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard ratios in current smokers were 1.7 (95% confidence interval, 1.3-2.2) for all-cause cardiovascular disease, 1.6 (1.1-2.1) for all-cause CHD, and 1.7 (1.2-2.4) for hard CHD. Similarly, among current smokers, hazard ratios were higher in the 4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1-6.6]). Both CAC>100 and high-sensitivity C-reactive protein ≥3 mg/L identified higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0 [1.5-6.0, compared with CAC=0] and 2.6 [1.4-4.8, compared with high-sensitivity C-reactive protein <2 mg/L], respectively). However, CAC was a stronger mediator of events and adversely modified the effect of smoking on events (eg, P-interaction=0.02 for hard CHD). Compared with never smokers, former smokers (median cessation interval=22 years) had similar adjusted hazard for events. In this multiethnic cohort, current smoking and cumulative exposure remain important modifiable determinants of cardiovascular disease. Both high-sensitivity C-reactive protein ≥3 mg/L and, particularly, CAC>100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.

Abdominal aortic calcium, coronary artery calcium, and cardiovascular morbidity and mortality in the Multi-Ethnic Study of Atherosclerosis.

To evaluate the predictive value of abdominal aortic calcium (AAC) for incident cardiovascular disease (CVD) independent of coronary artery calcium (CAC). We evaluated the association of AAC with CVD in 1974 men and women aged 45 to 84 years randomly selected from the Multi-Ethnic Study of Atherosclerosis participants who had complete AAC and CAC data from computed tomographic scans. AAC and CAC were each divided into following 3 percentile categories: 0 to 50th, 51st to 75th, and 76th to 100th. During a mean of 5.5 years of follow-up, there were 50 hard coronary heart disease events, 83 hard CVD events, 30 fatal CVD events, and 105 total deaths. In multivariable-adjusted Cox models including both AAC and CAC, comparing the fourth quartile with the ≤ 50th percentile, AAC and CAC were each significantly and independently predictive of hard coronary heart disease and hard CVD, with hazard ratios ranging from 2.4 to 4.4. For CVD mortality, the hazard ratio was highly significant for the fourth quartile of AAC, 5.9 (P=0.01), whereas the association for the fourth quartile of CAC (hazard ratio, 2.1) was not significant. For total mortality, the fourth quartile hazard ratio for AAC was 2.7 (P=0.001), and for CAC, it was 1.9, P=0.04. Area under the receiver operating characteristic curve analyses showed improvement for both AAC and CAC separately, although improvement was greater with CAC for hard coronary heart disease and hard CVD, and greater with AAC for CVD mortality and total mortality. Sensitivity analyses defining AAC and CAC as continuous variables mirrored these results. AAC and CAC predicted hard coronary heart disease and hard CVD events independent of one another. Only AAC was independently related to CVD mortality, and AAC showed a stronger association than CAC with total mortality.

Abstract P320: Discordance of Framingham Risk Score and Reynolds Risk Score to Global Vascular Risk Score: Results from the Hispanic Community Health Study/Study of Latinos

Introduction: The Framingham Risk Score (FRS) is a coronary heart disease (CHD) risk model established using an ethnically homogeneous population that predicts 10-year hard CHD events, myocardial infarction (MI) and coronary death. The Reynolds Risk Score (RRS) and Global Vascular Risk Score (GVRS) are validated CHD risk models that, in addition to hard CHD events, predict stroke and other CHD outcomes. In addition to major CHD risk factors, RRS adds systemic inflammation and family history of MI as GVRS adds behavioral and anthropometric measures. This study aims to compare agreement of RRS and GVRS with FRS among Hispanic/Latino adults and to describe discordance in RRS and GVRS with FRS categories, by socio-demographic characteristics. Methods: HCHS/SOL is a population-based cohort study of Hispanics/Latinos in four US communities. The analytic sample includes 6,058 non-diabetic participants 45-74 years of age with no past history of CHD and stroke who underwent comprehensive baseline examination. 10-year hard CHD risk score was calculated; participants were categorized as low (&lt;10%), moderate (10-&lt;20%), and high (≥20%) risk. Kappa scores were calculated to compare agreement of RRS and GVRS with FRS. Socio-demographic characteristics of concordance and discordance were characterized overall; multinomial logistic regression models was used to examine age-sex-adjusted likelihood of in discordance by these factors. Results: Mean age of the participants was 55 (SE=0.15) years, 54.3% were women, 41% had family history of CHD, and 90% were foreign born. Overall, 4,805 (74%) had low FRS, 1,143 (24%) had moderate FRS, and 110 (2%) had high FRS. There was poor agreement between RRS and FRS (Kappa=0.16, P&lt;0.01) and fair agreement between GVRS and FRS (Kappa=0.36, P&lt;0.01). In age-sex-adjusted analyses, RRS and GVRS were both more likely to classify persons of moderate and high risk who are between the ages of 60-74; GVRS classified more moderate and high risk women than the FRS. RRS and GVRS discordance with FRS was not associated with nativity and length of time in US. Conclusion: Significant discordance was observed between RRS and GVRS compared to FRS. Among Hispanic/Latino adults, use of RRS or GVRS may be more inclusive in classifying older age adults and women at high 10-year CHD risk.

Abstract 18536: Performance of Framingham Risk Function With Coronary Artery Calcium in Predicting Major Coronary Events in an Asian Cohort

Background: In non-White populations, the original Framingham risk functions (FRF) overestimates coronary heart disease (CHD) risk and requires recalibration. We tested whether the inclusion of coronary artery calcium (CAC) can improve the performance of the FRF in CHD prediction in an asymptomatic Asian cohort. Methods: We determined risk factors, CAC burden and CV outcomes in a sample of 4502 asymptomatic South Koreans (from the registry-based ESCORT Study) and in 3141 asymptomatic Caucasian participants from the Framingham Heart Study (FHS). Primary endpoint was a composite of cardiovascular death, myocardial infarction, and unstable angina with revascularization. We assessed both the discriminatory value of the original FRF before and after the addition of CAC using area under the receiver operator characteristic (AUC) and the calibration/predictive ability using the D’Agostino-Nam Chi squared test for survival data, where a chi-square statistic &gt; 20 indicates poor calibration. Results: There were 95 hard CHD events (45 ESCORT, 50 FHS) over a 55 month (ESCORT) and 60 month (FHS) follow-up period. For the FRF, the AUROC was 0.82, and the D’Agostino-Nam chi-squared statistic was 22.59 (p = 0.007) for predicting MACE in the ESCORT cohort. After the addition of CAC, the AUC improved to 0.85 and the D’Agostino-Nam chi-squared statistic improved to 16.14 (p = 0.064). The Caucasian-derived FRF model had poor predictive ability/calibration and consistently overestimated event rates in the Asian ESCORT cohort over all risk categories. For instance, in the 10th decile of risk, the predicted event rate using the FRF was 6% compared to an actual rate of 3.5% in the ESCORT cohort (Figure 1a) Conclusion: Addition of CAC to the classic Framingham risk functions significantly improves its performance in terms of discrimination and calibration in the prediction of major adverse CHD events in an Asian (South Korean) population.

Progression of Coronary Calcium and Incident Coronary Heart Disease Events

The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. Progression of CAC is associated with an increased risk for future hard and total CHD events.

Reclassification of Cardiovascular Risk in Patients With Normal Myocardial Perfusion Imaging Using Heart Rate Response to Vasodilator Stress

Previous studies have shown that patients with normal vasodilator myocardial perfusion imaging (MPI) findings remain at a greater risk of future cardiac events than patients with normal exercise MPI findings. The aim was to assess improvement in risk classification provided by the heart rate response (HRR) in patients with normal vasodilator MPI findings when added to traditional risk stratification. We retrospectively studied 2,000 patients with normal regadenoson or adenosine MPI findings. Risk stratification was performed using Adult Treatment Panel III framework. Patients were stratified by HRR (percentage of increase from baseline) into tertiles specific to each vasodilator. All-cause mortality and cardiac death/nonfatal myocardial infarction (MI) ≤2 years from the index MPI were recorded. During follow-up, 11.8% patients died and 2.7% patients experienced cardiac death/nonfatal MI in the adenosine and regadenoson groups, respectively. The patients who died had a greater Framingham risk score (12 ± 4 vs 11 ± 4, p= 0.009) and lower HRR (22± 16 vs 32 ± 21, p <0.0001). In an adjusted Cox model, the lowest tertile HRR was associated with an increased risk of mortality (hazard ratio 2.1) and cardiac death/nonfatal MI (hazard ratio 2.9; p <0.01). Patients in the highest HRR tertile, irrespective of the Adult Treatment Panel III category, were at low risk. When added to the Adult Treatment Panel III categories, the HRR resulted in net reclassification improvement in mortality of 18% and cardiac death/nonfatal MI of 22%. In conclusion, a blunted HRR to vasodilator stress was independently associated with an increased risk of cardiac events and overall mortality in patients with normal vasodilator MPI findings. The HRR correctly reclassified a substantial proportion of these patients in addition to the traditional risk classification models and identified patients with normal vasodilator MPI findings, who had a truly low risk of events.

Thoracic aortic calcification and coronary heart disease events: The multi-ethnic study of atherosclerosis (MESA)

The presence and extent of coronary artery calcium (CAC) is an independent predictor of coronary heart disease (CHD) morbidity and mortality. Few studies have evaluated interactions or independent incremental risk for coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established. This study used risk factor and computed tomography scan data from 6807 participants in the multi-ethnic study of atherosclerosis (MESA). Using the same images for each participant, TAC and CAC were each computed using the Agatston method. The study subjects were free of incident CHD at entry into the study. The mean age of the study population (n=6807) was 62±10 years (47% males). At baseline, the prevalence of TAC and CAC was 28% (1904/6809) and 50% (3393/6809), respectively. Over 4.5±0.9 years, a total of 232 participants (3.41%) had CHD events, of which 132 (1.94%) had a hard event (myocardial infarction, resuscitated cardiac arrest, or CHD death). There was a significant interaction between gender and TAC for CHD events (p<0.05). Specifically, in women, the risk of all CHD event was nearly 3-fold greater among those with any TAC (hazard ratio: 3.04, 95% CI: 1.60-5.76). After further adjustment for increasing CAC score, this risk was attenuated but remained robust (HR: 2.15, 95% CI: 1.10-4.17). Conversely, there was no significant association between TAC and incident CHD in men. In women, the likelihood ratio chi square statistics indicate that the addition of TAC contributed significantly to predicting incident CHD event above that provided by traditional risk factors alone (chi square=12.44, p=0.0004) as well as risk factors+CAC scores (chi square=5.33, p=0.02). On the other hand, addition of TAC only contributed in the prediction of hard CHD events to traditional risk factors (chi-square=4.33, p=0.04) in women, without contributing to the model containing both risk factors and CAC scores (chi square=1.55, p=0.21). Our study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.

Red Cell Distribution Width and Risk of Coronary Heart Disease Events

Red cell distribution width (RDW) has emerged as a powerful predictor of all-cause mortality in variety of cardiovascular settings. However, no data are available associating RDW with coronary heart disease (CHD) risk in a healthy and nationally representative multiethnic population. A total of 7,556 participants of the National Health and Nutrition Examination Surveys 1999 to 2006 (age 41.5 ± 15.8 years, 60% women) were divided into 3 categories according to their 10-year Framingham risk of hard CHD events: <10% (n = 6,173, reference category), 10% to 20% (n = 1,093, intermediate-risk category), and >20% (n = 290, high-risk category). Unadjusted and adjusted multivariate logistic regression analyses were performed evaluating RDW as a predictor of CHD risk. Each unit increase (0.1) in RDW posed a statistically significant greater odds of being in the intermediate-risk category (odds ratio -1.35, 95% confidence interval 1.27 to 1.45, p <0.001) and high-risk category (odds ratio -1.38, 95% confidence interval 1.25 to 1.53, p <0.001) compared to the reference category, after adjusting for race, body mass index, estimated glomerular filtration rate, hemoglobin A1c, C-reactive protein, hemoglobin, and mean corpuscular volume. Additional adjustments with serum iron, vitamin B(12), and folic acid levels did not affect the association. Subsequently, we divided participants into 2 categories according to their anemia status (as defined by the World Health Organization) to evaluate its effect. An RDW level greater than the seventy-fifth percentile in both anemic and nonanemic participants was a significant predictor of greater CHD risk while RDW of the seventy-fifth percentile or less in anemic participants failed to predict CHD (compared to nonanemic participants with similar RDW as the reference category). In conclusion, a higher RDW appears to be a powerful independent predictor of future CHD risk.

Cardiovascular events with absent or minimal coronary calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)

Elevated coronary artery calcium (CAC) is a marker for increase risk of coronary heart disease (CHD). Although most CHD events occur among individuals with advanced CAC, CHD can also occur in individuals with little or no calcified plaque. In this study, we sought to evaluate the characteristics associated with incident CHD events in the setting of minimal (score <or=10) or absent CAC (score of zero). Asymptomatic participants in the MESA (N = 6,809) were followed for occurrence of all CHD events (including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death) and hard CHD events (myocardial infarction or CHD death). Time to incident CHD was modeled using age-and gender-adjusted Cox regression. The final study population consisted of 3,923 MESA asymptomatic participants (mean age 58 +/- 9 years, 39% males) who had CAC scores of 0 to 10. Overall, no detectable CAC was seen in 3415 individuals, whereas 508 had CAC scores of 1 to 10. During follow-up (median 4.1 years), there were 16 incident hard events and 28 all CHD events in individuals with absent or minimal CAC. In age-, gender-, race-, and CHD risk factor-adjusted analysis, minimal CAC (1-10) was associated with an estimated 3-fold greater risk of a hard CHD event (HR 3.23, 95% CI 1.17-8.95) or of all CHD event (HR 3.66, 95% CI 1.71-7.85) compared to those with CAC = 0. Former smoking (HR 3.57, 95% CI 1.08-11.77), current smoking (HR 4.93, 95% CI 1.20-20.30), and diabetes (HR 3.09, 95% CI 1.07-8.93) were significant risk factors for events in those with CAC = 0. Asymptomatic persons with absent or minimal CAC are at very low risk of future cardiovascular events. Individuals with minimal CAC (1-10) were significantly increased to 3-fold increased risk for incident CHD events relative to those with CAC scores of zero.

Associations of factor VIIIc, D‐dimer, and plasmin–antiplasmin with incident cardiovascular disease and all‐cause mortality

To examine the associations of three understudied hemostatic factors--D-dimer, factor VIII(c), and plasmin-antiplasmin (PAP) complex--with incident cardiovascular disease (CVD) and all cause mortality in the Multiethnic Study of Atherosclerosis cohort. Hemostatic factors were measured at baseline in 45-84-year-old patients (n = 6,391) who were free of clinically recognized CVD. Over 4.6 years of follow-up, we identified 307 CVD events, 207 hard coronary heart disease events, and 210 deaths. D-dimer, factor VIII(c), and PAP were not associated with CVD incidence after adjustment for other risk factors. In contrast, each factor was associated positively with total mortality, and D-dimer and factor VIII(c) were associated positively with cancer mortality. When modeled as ordinal variables and adjusted for risk factors, total mortality was greater by 33% (95% CI 15-54) for each quartile increment of D-dimer, 26% (11-44) for factor VIIIc, and 20% (4-38) for PAP. This prospective cohort study did not find D-dimer, factor VIII(c), or PAP to be risk factors for CVD. Instead, elevated levels of these three hemostatic factors were associated independently with increased risk of death. Elevated D-dimer and factor VIII(c) were associated with increased cancer death.

Abstract 2231: Thoracic Aortic Calcification and Coronary Heart Disease Events: the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The presence of coronary artery calcium (CAC) is an independent marker of cardiovascular disease (CVD) events and mortality. However, the predictive value of thoracic aorta calcification (TAC), which can be additionally examined without further scanning during assessment of CAC, in predicting coronary heart disease (CHD) events in asymptomatic women and men, is not well-established. Methods: We collected data on risk factors and performed scanning for both TAC and CAC in a multi-ethnic population-based cohort of 6809 individuals (62±10 years, 47% males). Using the same images for each participant, TAC and CAC were computed using the Agatston method. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 4.1 years. Results: The mean age of the study population was 62±10 years (47% males). At baseline 1904 (28%) participants had detectable TAC, whereas 3392 (50%) had CAC&gt;0. During the follow-up interval, 189 (2.78%) and 108 (1.59%) participants suffered any CHD and hard CHD event, respectively. Table below provide the hazard ratio (95% CI) for coronary events with presence of TAC. Overall TAC was a stronger predictor of CHD risk in women than in men. . Conclusion: Our study result suggests that TAC imparts independent prognostic power to predict future coronary events in women and may provide rationale for more intensive risk factor modification. Hazard Ratios (95% CI) of All CHD and Hard CHD Events with TAC (TAC&gt;0 vs. TAC=0)