Traditional Coronary Heart Disease Risk Research Articles

Can We Mitigate Coronary Heart Disease Risk in Patients with Cancer?

The review focuses on the shared risk factors observed between coronary heart disease and cancer, cancer therapeutics causing coronary heart disease, and potential strategies to mitigate atherosclerosis in patients with cancer. The pathophysiology behind how traditional cardiovascular risk factors also contribute to cancer development and mortality is increasingly recognized. In addition, newer cancer therapies, such as immune checkpoint inhibitors, cause increased inflammation leading to increased cardiovascular events. Traditional coronary heart disease risk factors such as obesity, hypertension, diabetes, and hyperlipidemia also contribute to cancer development and worse cancer outcomes. Cancer therapeutics can also lead to atherosclerotic events in addition to the shared risk factors present at the time of cancer diagnosis. Understanding the pathophysiology, using multidisciplinary care teams, and developing machine learning algorithms for individualized patient care will help to mitigate the risk of coronary heart disease in patients with cancer.

Use of Artificial Intelligence in Coronary Artery Calcium Scoring.

Coronary artery calcium (CAC) scoring improves traditional risk factor-based coronary heart disease (CHD) risk stratification. Here, the contribution of CAC scoring to a traditional 10-year CHD risk prediction scores and new artificial intelligence methods used to automate CAC scoring were reviewed. Research shows that traditional risk factors tend to overestimate or underestimate the actual risk of CHD, meaning that including CAC score in the risk stratification has potential to reduce over- and undertreatment. The automated CAC scoring methods are shown to be accurate and significantly more time-effective than the commonly used semi-automated method.

Usefulness of Higher Levels of Cardiac Troponin T in Patients With Stable Angina Pectoris to Predict Risk of Acute Myocardial Infarction

In patients with stable angina, the association between high-sensitivity cardiac troponin T (hs-cTnT) and incident acute myocardial infarction (AMI), as well as pathophysiologic mechanisms accounting for an adverse prognosis, remain to be determined. We explored the association between hs-cTnT and future AMI among 3,882 patients evaluated for suspected stable angina pectoris and investigated to which extent hs-cTnT attenuated the relations between traditional coronary heart disease (CHD) risk factors and AMI. Associations between increasing hs-cTnT categories (≤3, 4 to 9, 10 to 19, and 20 to 30 ng/L) and risk of AMI were studied by Cox regression. We investigated whether the associations between traditional CHD risk factors and future AMI were influenced by adjusting for hs-cTnT. Median age was 62 years. During median (25th to 75th percentile) 8 (6.4 to 8.7) years of follow-up, 460 (11.8%) experienced an AMI. There was a strong association between hs-cTnT categories and risk of AMI. The relation was somewhat attenuated, but still present, when adjusting for potential confounders, traditional CHD risk factors, previous peripheral vascular disease, and percutaneous coronary intervention or coronary bypass surgery. Moreover, hs-cTnT slightly attenuated the risk relations between traditional CHD risk factors and incident AMI, but each risk factor remained significantly associated with AMI. In conclusion, among patients with suspected stable angina, hs-cTnT was positively related to incident AMI.

Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry.

Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08-2.82) and hypertension (2.48; 1.92-3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86-28.86) and use of >1 LDL-lowering medication (1.80; 1.34-2.41). FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.

Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris.

BackgroundGlycine is an amino acid involved in antioxidative reactions, purine synthesis, and collagen formation. Several studies demonstrate inverse associations of glycine with obesity, hypertension, and diabetes mellitus. Recently, glycine‐dependent reactions have also been linked to lipid metabolism and cholesterol transport. However, little evidence is available on the association between glycine and coronary heart disease. Therefore, we assessed the association between plasma glycine and acute myocardial infarction (AMI).Methods and ResultsA total of 4109 participants undergoing coronary angiography for suspected stable angina pectoris were studied. Cox regression was used to estimate the association between plasma glycine and AMI, obtained via linkage to the CVDNOR project. During a median follow‐up of 7.4 years, 616 patients (15.0%) experienced an AMI. Plasma glycine was higher in women than in men and was associated with a more favorable baseline lipid profile and lower prevalence of obesity, hypertension, and diabetes mellitus (all P<0.001). After multivariate adjustment for traditional coronary heart disease risk factors, plasma glycine was inversely associated with risk of AMI (hazard ratio per SD: 0.89; 95% CI, 0.82–0.98; P=0.017). The inverse association was generally stronger in those with apolipoprotein B, low‐density lipoprotein cholesterol, or apolipoprotein A‐1 above the median (all P interaction≤0.037).ConclusionsPlasma glycine was inversely associated with risk of AMI in patients with suspected stable angina pectoris. The associations were stronger in patients with apolipoprotein B, low‐density lipoprotein cholesterol, or apolipoprotein A‐1 levels above the median. These results motivate further studies to elucidate the relationship between glycine and lipid metabolism, in particular in relation to cholesterol transport and atherosclerosis.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00354081.

Epidemiology of coronary heart disease in patients with human immunodeficiency virus.

As a growing number of patients infected with human immunodeficiency virus (HIV) have access to antiretroviral therapy and achieve virologic suppression, the focus of clinical care is shifting from treating the infectious complications of advanced immunodeficiency to managing and preventing chronic disease. The aging of the HIV-positive population and increased rates of chronic disease complications in the setting of HIV infection have increased the impact of noncommunicable diseases such as coronary heart disease (CHD). The effect of HIV on CHD is independent of traditional cardiovascular risk factors and antiretroviral medications and is likely due in part to the chronic inflammation and immune activation underlying HIV infection. This article describes the current state of epidemiologic knowledge on CHD in HIV infection. It highlights key studies in the field and summarizes epidemiologic data with respect to traditional and novel CHD risk factors, specialized clinical subgroups, and broader cardiovascular outcomes.

Association Between Persistence with Statin Therapy and Reduction in Low-Density Lipoprotein Cholesterol Level: Analysis of Real-Life Data from Community Settings

To validate the use of drug dispensing data as a measure of drug exposure and to quantify the association between persistence with statin therapy and low-density lipoprotein cholesterol (LDL) levels using real-life community data. Retrospective, population-based cohort study. Maccabi Healthcare Services (MHS) database, which contains linked prescription drug information, hospitalization records, and laboratory test results of 2million members of the second largest health organization in Israel. A total of 87,219 primary prevention patients and 15,139 secondary prevention patients who were MHS members and who started statin therapy between 1998 and 2008. Baseline and follow-up LDL levels were documented from 3months before the date of first dispensed statin (index date) to 6months afterward. Persistence was assessed by proportion of days covered (PDC) with statins during the follow-up period. Over the follow-up period, significant (p<0.001) reductions in LDL levels of 54, 33, and 13mg/dl were noted among highly persistent (PDC≥80%), moderately persistent (34%≤PDC<79%), and poorly persistent statins users (PDC≤33%), respectively. The reduction was observed as early as 2-3weeks after therapy initiation. In a multivariable model controlling for baseline LDL level and traditional coronary heart disease risk factors (diabetes mellitus, hypertension), high persistence with statin therapy was associated with a 27% and 25% decrement in LDL level among the primary and secondary prevention cohorts, respectively. Similarly, a higher proportion of the persistent statins users reached their target LDL level within the study follow-up period: 80% and 58% among primary and secondary prevention cohorts, respectively, compared with only 28% and 17%, respectively, among poorly persistent patients. In this observational population-based study, calculated PDC with statins during study follow-up was strongly associated with drug effect of LDL level reduction. The results agree with previous estimates of statin efficacy from randomized clinical trials, supporting the validity of using PDC methods as a measure of drug exposure.

Abstract MP46: Dietary Pattern and Risk of Sudden Cardiac Death in Post-Menopausal Women

Background: The Mediterranean Diet and Dietary Approaches to Stop Hypertension (DASH) diet are characterized by higher intake of fruits, vegetables, whole grains, and unsaturated fatty acids. All of these foods/nutrients may affect cholesterol, inflammation, the development of atherosclerosis, and therefore risk of sudden cardiac death (SCD). Furthermore, the DASH diet is known to lower blood pressure and hypertension is a major risk factor for SCD. Objective: To examine the association between the Mediterranean and DASH dietary patterns and risk of SCD in women. Methods: Post-menopausal women enrolled in the Women’s Health Initiative observational study (n = 93,676) completed a food frequency questionnaire at enrollment and at year three. Women enrolled at 40 clinical sites across the U.S. between 1993 and 1998, and were followed for an average of 10.5 years. We scored their diets according to how closely reported diet resembled each dietary pattern. SCD was defined as death occurring within one hour of symptom onset. We estimated risk of SCD according to quintile of dietary pattern score using hazard models with time-varying exposures. Results: A higher Mediterranean diet score was associated with a lower risk of SCD: women in the highest quintile, or who came closest to following the Mediterranean dietary pattern, had a HR of 0.62 (95% CI 0.41-0.93) compared to women in the lowest quintile, after adjustment for age, total energy, race, income, smoking, and physical activity (Table). After adjusting for other traditional coronary heart disease risk factors which are potential mediators, the association remained statistically significant: HR 0.65 (95% CI 0.43-0.99). A higher DASH diet score was not associated with reduced risk of SCD. However, sodium intake, a crucial component of the DASH dietary pattern, was not well-characterized by the FFQ. Conclusions: The Mediterranean dietary pattern may be associated with a lower risk of SCD in post-menopausal women, however there was no indication of a dose-response relationship.

Effects of the Addition ofT'ai Chito a Dietary Weight Loss Program on Lipoprotein Atherogenicity in Obese Older Women

To examine the additive effect of t'ai chi (TC) to diet education on the traditional coronary heart disease (CHD) risk factor low-density lipoprotein cholesterol (LDL-C) and on emerging CHD risk factors (apolipoprotein B and LDL particle size) in older obese women. Ancillary study of a randomized clinical trial. University of Rhode Island. 26 obese women (mean age±standard deviation, 61.5±6.0 years; mean body mass index, 34.3±4.0 kg/m(2)) were enrolled and randomly assigned to the diet education group (n=13) or the diet education plus TC group (n=13). All participants received 45 minutes of diet education per week. The diet education plus TC group also received 45 minutes of TC three times per week for 16 weeks. Anthropometrics (height, weight, BMI, waist circumference, and hip circumference), clinical variables (blood pressure), and biochemical variables (standard lipid profile, apolipoprotein B, LDL particle size) were measured. The primary outcome was LDL-C, and the secondary outcomes were apolipoprotein B and LDL particle size. Neither LDL-C nor apolipoprotein B improved in either group. Percentage of large LDL particles after the intervention was increased in the diet education plus TC group compared with the diet education group. Weight, waist circumference, and high-density lipoprotein cholesterol decreased in both groups from baseline to post-intervention. Triacylglycerol and dietary screening tool scores increased in both groups. Additional improvements were seen in the diet education plus TC group, including a significant increase in Dietary Approaches to Stop Hypertension score from baseline to post-intervention. The addition of TC to diet education is more effective than diet education alone at improving diet quality and emerging CHD risk factors, such as LDL particle size, in obese older women.

Number of Coronary Heart Disease Risk Factors and Mortality in Patients With First Myocardial Infarction

Few studies have examined the association between the number of coronary heart disease risk factors and outcomes of acute myocardial infarction in community practice. To determine the association between the number of coronary heart disease risk factors in patients with first myocardial infarction and hospital mortality. Observational study from the National Registry of Myocardial Infarction, 1994-2006. We examined the presence and absence of 5 major traditional coronary heart disease risk factors (hypertension, smoking, dyslipidemia, diabetes, and family history of coronary heart disease) and hospital mortality among 542,008 patients with first myocardial infarction and without prior cardiovascular disease. All-cause in-hospital mortality. A majority (85.6%) of patients who presented with initial myocardial infarction had at least 1 of the 5 coronary heart disease risk factors, and 14.4% had none of the 5 risk factors. Age varied inversely with the number of coronary heart disease risk factors, from a mean age of 71.5 years with 0 risk factors to 56.7 years with 5 risk factors (P for trend < .001). The total number of in-hospital deaths for all causes was 50,788. Unadjusted in-hospital mortality rates were 14.9%, 10.9%, 7.9%, 5.3%, 4.2%, and 3.6% for patients with 0, 1, 2, 3, 4, and 5 risk factors, respectively. After adjusting for age and other clinical factors, there was an inverse association between the number of coronary heart disease risk factors and hospital mortality adjusted odds ratio (1.54; 95% CI, 1.23-1.94) among individuals with 0 vs 5 risk factors. This association was consistent among several age strata and important patient subgroups. Among patients with incident acute myocardial infarction without prior cardiovascular disease, in-hospital mortality was inversely related to the number of coronary heart disease risk factors.

Ultrasound Imaging of Carotid Intima-Media Thickness: an Office-Based Tool to Assist Physicians in Cardiovascular Risk Assessment

Traditional coronary heart disease risk prediction schemes such as the Framingham Risk Score, although useful, do not adequately identify all individuals who experience an adverse coronary heart disease event. Therefore, additional tools, including biomarkers, genetic markers, and imaging markers, are being evaluated for their value in improving cardiovascular risk assessment. Of the two accepted imaging markers of atherosclerosis, namely coronary artery calcium score (CACS) measured by CT scan and carotid intima-media thickness (CIMT) measured by ultrasound, CIMT has the potential to be widely adopted as a clinical tool for physician offices. Ultrasound-based CIMT measurement is safe but has several challenges, including reproducibility and operator-dependency. We review and present data with respect to the added value of CIMT and information about plaque presence or absence in improving coronary heart disease risk prediction and further provide information related to adequate scanning protocols. New developments in the area of automated CIMT measurement, three-dimensional, ultrasound-based plaque volume estimation are promising and have the potential to create a quantum leap in our ability to measure, characterize, and monitor carotid atherosclerosis and in turn prediction of cardiovascular disease risk.

Do changes in traditional coronary heart disease risk factors over time explain the association between socio-economic status and coronary heart disease?

BackgroundSocioeconomic status (SES) predicts coronary heart disease independently of the traditional risk factors included in the Framingham risk score. However, it is unknown whether changes in Framingham risk score variables over time explain the association between SES and coronary heart disease. We examined this question given its relevance to risk assessment in clinical decision making.MethodsThe Atherosclerosis Risk in Communities study data (initiated in 1987 with 10-years follow-up of 15,495 adults aged 45-64 years in four Southern and Mid-Western communities) were used. SES was assessed at baseline, dichotomized as low SES (defined as low education and/or low income) or not. The time dependent variables - smoking, total and high density lipoprotein cholesterol, systolic blood pressure and use of blood pressure lowering medication - were assessed every three years. Ten-year incidence of coronary heart disease was based on EKG and cardiac enzyme criteria, or adjudicated death certificate data. Cox survival analyses examined the contribution of SES to heart disease risk independent of baseline Framingham risk score, without and with further adjustment for the time dependent variables.ResultsAdjusting for baseline Framingham risk score, low SES was associated with an increased coronary heart disease risk (hazard ratio [HR] = 1.53; 95% Confidence Interval [CI], 1.27 to1.85). After further adjustment for the time dependent variables, the SES effect remained significant (HR = 1.44; 95% CI, 1.19 to1.74).ConclusionUsing Framingham Risk Score alone under estimated the coronary heart disease risk in low SES persons. This bias was not eliminated by subsequent changes in Framingham risk score variables.

Genetic and Environmental Influences on the Plasma Interleukin-6 Concentration in Patients with a Recent Myocardial Infarction: A Case–Control Study

The aim was to study the stimuli responsible for triggering and sustaining the plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients with a first myocardial infarction before the age of 60 and healthy control subjects matched for age and sex. The plasma IL-6 concentration, antibodies against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single-nucleotide polymorphism were determined 3 months after the acute event. The results showed that patients had higher IL-6 levels than control subjects, whereas there were no differences regarding individual or total number (pathogen burden) of positive antibody tests against the different pathogens or IL6 genotype distribution. The plasma IL-6 concentration was associated with the number of positive antibody tests in patients and control subjects, whereas patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis, including traditional coronary heart disease risk factors, antibodies against pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6 concentration. Neither pathogen burden nor IL6 genotype did contribute to the variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension, case-control status, and age were determinants of the plasma IL-6 concentration.

Are Changes in Cardiovascular Disease Risk Factors in Midlife Women Due to Chronological Aging or to the Menopausal Transition?

This prospective study examined whether changes in traditional and novel coronary heart disease (CHD) risk factors are greater within a year of the final menstrual period (FMP), relative to changes that occur before or after that interval, in a multiethnic cohort. Understanding the influence of menopause on CHD risk remains elusive and has been evaluated primarily in Caucasian samples. SWAN (Study of Women's Health Across the Nation) is a prospective study of the menopausal transition in 3,302 minority (African American, Hispanic, Japanese, or Chinese) and Caucasian women. After 10 annual examinations, 1,054 women had achieved an FMP not due to surgery and without hormone therapy use before FMP. Measured CHD risk factors included lipids and lipoproteins, glucose, insulin, blood pressure, fibrinogen, and C-reactive protein. We assessed which of 2 models provided a better fit with the observed risk factor changes over time in relation to the FMP: a linear model, consistent with chronological aging, or a piecewise linear model, consistent with ovarian aging. Only total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B demonstrated substantial increases within the 1-year interval before and after the FMP, consistent with menopause-induced changes. This pattern was similar across ethnic groups. The other risk factors were consistent with a linear model, indicative of chronological aging. Women experience a unique increase in lipids at the time of the FMP. Monitoring lipids in perimenopausal women should enhance primary prevention of CHD.

Emerging inflammatory markers for assessing coronary heart disease risk

Although assessment of traditional coronary heart disease risk factors can often stratify individuals into low- or high-risk categories, additional means are needed to more precisely classify people clinically defined as intermediate-risk, to guide the intensity of risk-reducing therapies. The recognition that inflammatory pathways are important in the progression of atherosclerosis and its complications has prompted investigation to identify circulating risk markers that may be useful in risk stratification. This article summarizes recent studies on the current use of an emerging group of inflammatory markers: soluble CD-40 ligand, interleukin-18, myeloperoxidase, B-type natriuretic peptides, secretory phospholipase A(2), lipoprotein-associated phospholipase A(2), and C-reactive protein. The demonstration that lowering C-reactive protein along with low-density lipoprotein cholesterol with statins reduces events beyond cholesterol lowering alone suggests that titration of therapies using other emerging inflammatory markers may further reduce the toll of atherosclerosis in adult populations.

Gender differences in risk factors and outcomes after cardiac rehabilitation

Objective — We compared the baseline characteristics, cardiovascular risk factors and outcomes between men and women in an Iranian cardiac rehabilitation programme after adjusting for age, body mass index and waist-to-hip ratio.Methods — In a self-controlled descriptive study performed between 1996 and 2006, we evaluated 547 patients with documented coronary heart disease before and after a 24-session cardiac rehabilitation programme.Results — Women were older, more likely to be obese, anxious, depressed, and had more traditional coronary heart disease risk factors than men. At baseline, exercise capacity was lower (P < 0.001), but total cholesterol (P < 0.001), high-density lipoprotein cholesterol (P = 0.007), lowdensity lipoprotein cholesterol (P = 0.001), fasting blood sugar (P = 0.002), left ventricular ejection fraction (P < 0.001), systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.001), and heart rate (P = 0.016) were higher in women. Although there was significant improvement in most of the variables and risk factors after cardiac rehabilitation, changes were not statistically significant between men and women except for significantly more improvement in exercise capacity (P < 0.001) and less reduction in body mass index (P = 0.04) in men.Conclusion — Following a short-term cardiac rehabilitation programme, modification in cardiac risk factors and quality of life occurs. Both genders benefit alike in most aspects from this programme.

High Prevalence of Cardiometabolic Risk Factors in Women Considered Low Risk by Traditional Risk Assessment

Cardiovascular disease (CVD) is the leading cause of death in women in the United States. The purpose of this study was to characterize the prevalence and awareness of traditional CVD risk factors, obesity, and coronary heart disease (CHD) risk classification using the Framingham Risk Score (FRS) among women attending the 2006 Sister to Sister National Woman's Heart Day event. A total of 8936 participants (mean age 49 +/- 14 years) were evaluated. There was a modest prevalence of traditional risk factors on screening, including non-high-density lipoprotein-cholesterol (HDL-C) >160 mg/dL (27%), HDL-C <40 mg/dL (16%), random glucose level >140 mg/dL (6%), uncontrolled blood pressure > or =140/90 mm Hg (12%), current smoking (6%), and a positive family history of CHD (21%). There was a high prevalence of overweight (39%) or obese individuals (35%) (body mass index [BMI] 25-30 and > or =30 kg/m(2), respectively), as well as those with high waist circumference (> or =35 inches) (55%). Women were classified by FRS as low (85%), intermediate (6%), and high risk (9%). When cardiometabolic risk analyses included waist circumference in addition to the FRS, 59% of low-risk and 50% of intermediate-risk women had 1 or 2 risk factors, and 19% and 41% had > or =3 risk factors, respectively. Women were often unaware of risk factors on screening; among women without a previous diagnosis of dyslipidemia or hypertension, 48% and 7%, respectively, were given new diagnoses. Women participating in the 2006 Sister to Sister National Woman's Heart Day event have a high prevalence of cardiometabolic risk factors, especially dyslipidemia, obesity, and high central adiposity, that place them at higher risk for the development of CVD and other comorbidities. The newly identified multiple risk factors in this population support the value of community health screening in women.

Heritability of flow-mediated dilation: a twin study.

Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker for early atherosclerotic vascular disease and future cardiovascular events. To estimate the heritability of brachial artery FMD using a twin design. We estimated the heritability of FMD using 94 middle-aged male twin pairs. FMD was measured by ultrasound, and traditional coronary heart disease risk factors were measured. Genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in FMD. The mean age of the twin participants was 54.9 +/- 2.8 years. The mean FMD was 0.047 +/- 0.030. The intraclass correlation coefficient was higher in MZ twins [0.38, 95% confidence interval (CI) 0.32-0.43] than in DZ twins (0.19, 95% CI 0.11-0.26), suggesting a role of genetic influence in FMD variation. Structural equation modeling showed that both genetic and unique environmental factors contributed significantly to the variation in FMD. The crude FMD heritability was 0.37 (95% CI 0.15-0.54). After adjustment for traditional cardiovascular risk factors, including age, total cholesterol, blood pressure, and body mass index, the heritability of FMD was 39% (95% CI 0.18-0.56). The remaining variation in FMD could be explained by individual-specific environment. This is the first study using twins to estimate the relative contributions of genetics and environment to the variation in FMD in a US population. Our results demonstrate a moderate genetic effect on brachial artery FMD, independent of traditional coronary risk factors. Our data also highlight the importance of unique environment on the variability in FMD.

Pathobiological Determinants of Atherosclerosis in Youth Risk Scores Are Associated With Early and Advanced Atherosclerosis

Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.

Nontraditional CHD Risk Markers: How Much Value Do They Add?

Traditional coronary heart disease (CHD) risk factors do not identify a substantial proportion of people who develop CHD, prompting interest in nontraditional markers for enhancing risk prediction. These researchers assessed the predictive value of 19 nontraditional markers, including C-reactive protein (CRP), among 15,792 participants (age 45–74) in the Atherosclerosis Risk in Communities (ARIC) study. Many of the nontraditional markers, including CRP, …