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Biomedical subjects

Roger S Blumenthal

Publications and source records attributed to Roger S Blumenthal.

At least 19 recordsLinked to original sources
PubMed2007

High-density lipoprotein cholesterol: a potential therapeutic target for prevention of coronary artery disease.

High-density lipoprotein cholesterol has an important role in the pathophysiology of coronary artery disease. High-density lipoprotein cholesterol is becoming an increasingly important prognostic and therapeutic target. The purpose of this paper is to review the biochemical pathways involved in reverse cholesterol transport and to discuss potential, clinically based high-density lipoprotein therapies that may contribute to reduction in risk of atherosclerosis.

ATP-Binding Cassette Transporters↗
PubMed2006

Relation of uric acid levels to presence of coronary artery calcium detected by electron beam tomography in men free of symptomatic myocardial ischemia with versus without the metabolic syndrome.

The objective of this study was to evaluate whether uric acid (UA) levels were associated with coronary artery calcium (CAC) in white men asymptomatic for coronary heart disease. We also evaluated whether this relation was dependent or not on the presence of the metabolic syndrome (MS). The study population consisted of 371 asymptomatic Brazilian men (48 +/- 7 years of age) who underwent a routine evaluation. The average 10-year total risk of coronary heart disease calculated by Framingham risk score was 10.8 +/- 7.8%. The age-adjusted prevalence of CAC in patients with a high UA level (fourth quartile > or =7.1 mg/dl, n = 91) was significantly higher than that in those with a normal UA level (58% vs 44%, p = 0.02). With respect to age, smoking, physical activity, and components of MS-adjusted analyses, a high UA level was independently associated with the presence of CAC (p = 0.043) and with increasing levels of CAC (p = 0.028). Prevalence of MS showed a graded increase according to serum UA values. In patients with the MS, after adjusting for age, smoking, physical activity, and white blood cell count, high levels of UA were strongly associated with the presence of any CAC (odds ratio 3.47, 95% confidence interval 1.26 to 9.53, p = 0.01) and with increasing levels of CAC (odds ratio 2.74, 95% confidence interval 1.15 to 6.50, p = 0.02). Conversely, there was no significant association of high UA levels in patients without the MS. However, the interaction between high UA level and the MS did not achieve statistical significance for the presence of CAC (p = 0.11) or higher levels of CAC (p = 0.16). In conclusion, our study suggests that, among asymptomatic moderate-risk men, high UA levels were independently associated with CAC in subjects with the MS.

Brazil↗
PubMed2006

Implications of C-reactive protein or coronary artery calcium score as an adjunct to global risk assessment for primary prevention of CHD.

BACKGROUND: C-reactive protein (CRP) or coronary artery calcium (CAC) score have been suggested to identify a higher risk subset of intermediate-risk individuals, who potentially could be considered for more aggressive therapy. In the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated the proportion of intermediate-risk participants whose risk status might change based on additional testing using CRP and/or CAC score. METHODS: Framingham 10-year CHD risk scores (FRS) were calculated and cross tabulations were used to determine the percent of individuals at intermediate-risk by FRS with a CRP >3mg/L and/or CAC score >100 AU. Similar analyses were performed using the gender-specific 75th percentile for CRP and CAC. RESULTS: Of the 30% of participants (N=1450) classified as intermediate-risk by FRS, 30% had a CRP >3mg/L and 33% had a CAC score >100 AU. Among intermediate-risk women, 49% had a CRP >3mg/L compared to 27% of intermediate-risk men (p<0.0001) while the same percent of intermediate-risk women and men (33%) had a CAC score >100 AU. Eleven percent or less of men or women had both a high CRP and CAC score whether conventional or gender-specific cut points were used. When the percent of intermediate-risk individuals with an elevated CRP and/or CAC score in MESA were applied to NHANES III data, over a million intermediate-risk individuals would move to high risk status if CRP or CAC screening directed treatment strategies were uniformly adopted in the U.S. CONCLUSION: There were differences in the number of intermediate-risk individuals reclassified as high risk depending on the screening test used, the cut points selected, and the demographics of the individuals being screened. These data highlight current limitations of broadly using risk markers such as CRP and CAC score in an intermediate-risk population.

Aged↗
PubMed2006

Relationship of subclinical coronary atherosclerosis and National Cholesterol Education Panel guidelines in asymptomatic Brazilian men.

BACKGROUND AND OBJECTIVE: Coronary heart disease (CHD) is the leading cause of death worldwide including Brazil. Improved precision in detecting early coronary disease may aid in more targeted preventive therapy. The National Cholesterol Education Program (NCEP) provides guidelines for determining the aggressiveness of primary prevention strategies including lipid lowering based on Framingham risk equation. Identification of subclinical atherosclerosis and coronary plaque burden is a step towards identifying high-risk individuals. This investigation was designed to determine how the updated NCEP guidelines classify asymptomatic individuals with presence of any as well as advanced CACS (coronary artery calcium score), a powerful intermediary for CHD events, in asymptomatic Brazilian men. METHODS AND RESULTS: Five hundred forty-six asymptomatic Brazilian men (mean age: 46+/-7 years) presented to a single electron beam tomography (EBT) facility in Sao Paulo. The study population was categorized into low risk (0-1 risk factors, n=166, 30%), intermediate risk (> or = 2 risk factors but < 10% risk of CHD over 10 years, n=150, 27%), moderately high risk (2 risk factors and 10-20% risk of hard CHD events in 10 years, n=147, 28%) and high-risk (> or = 2 risk factors and > 20% risk of hard CHD events in 10 years, n=83, 15%), respectively. In our study population, overall no CACS, mild CACS (1-99.9), moderate-severe CACS (> or = 100) were observed in 317 (58%), 160 (29%) and 69 (13%) men, respectively. Advanced calcification (CACS > or = 75th percentile for age) was present in 19% (n=104) men. Based on the LDL-C cutoffs recommended by the NCEP guidelines for initiation of lipid lowering, overall only 55% with CACS > or = 100 and 42% men with CACS > or = 75th percentile qualified for pharmacotherapy. As a result nearly half of individuals with CACS > or = 100 (45%) and CACS > or = 75th percentile (48%) missed eligibility for drug therapy. CONCLUSION: Our findings reveal the potential limitation of NCEP guidelines in identifying asymptomatic Brazilian men with significant coronary atherosclerosis who are potential candidates for aggressive primary prevention. Assessment of CACS may provide incremental value to global risk assessment in high-risk Brazilian men.

Adult↗
PubMed2006

Dyslipidemia prevalence, treatment, and control in the Multi-Ethnic Study of Atherosclerosis (MESA): gender, ethnicity, and coronary artery calcium.

BACKGROUND: To assess the implementation challenge facing the Third Report of the Adult Treatment Panel (ATP III) of the National Cholesterol Education Program, we determined the prevalence, treatment, and control of dyslipidemia, including ethnic and gender differences, in persons free of known clinical cardiovascular disease (CVD). In addition, this report provides information about the presence of coronary artery calcium (CAC) across groups defined by risk and recommendations for the use of lipid-lowering drugs. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study of 6814 persons aged 45 to 84 years who were free of clinical CVD at baseline (2000-2002). Participants with complete fasting lipid profiles (n=6704) were evaluated for CVD risk and self-reported use of lipid-lowering therapy. CAC was assessed by CT. Drug treatment thresholds and goals were defined according to ATP III. Models were constructed to adjust for age, clinic site, risk factors, socioeconomic characteristics, and healthcare access variables with the use of Poisson regression. Overall, 29.3% (1964/6704) had dyslipidemia, among whom lipid-lowering drug therapy was reported by 54.0% (1060/1964). Control to ATP III goal was observed in 75.2% (797/1060) of participants with treated dyslipidemia and 40.6% (797/1964) of participants with dyslipidemia. Men were more likely than women to qualify for drug therapy and less likely to be treated and controlled. Relative to non-Hispanic whites, Chinese Americans were less likely to qualify for drug treatment, but no differences in treatment and control rates were observed. Black and Hispanic Americans had prevalence of dyslipidemia that was comparable to that of non-Hispanic whites but were less likely to be treated and controlled. Ethnic disparities were attenuated substantially by adjustment for healthcare access variables; however, the gender disparities persisted despite adjustment for risk factors, socioeconomic characteristics, and healthcare access variables. Control of dyslipidemia was achieved less commonly in the CVD high- and intermediate-risk groups than in the low-risk group. Among high-risk individuals, 19.7% of those who did not qualify for lipid-lowering drug treatment had CAC >400. The proportion of drug treatment-qualifying persons who were not treated differed by presence and severity of CAC, with 48.0%, 46.8%, and 39.6% of eligible persons with no CAC, with CAC >0 and <400, and with CAC >400 not receiving treatment, respectively (P for difference=0.04). CONCLUSIONS: Dyslipidemia is common among persons without CVD. The quality of care for dyslipidemia is suboptimal in general and variable by CVD risk group, ethnicity, and gender. The utility of incorporating CAC screening into the risk stratification and treatment process should be investigated in light of the substantial proportions of persons with CAC who are currently classified as not requiring treatment. Research and quality improvement programs are needed to optimize management of dyslipidemia.

Aged↗
PubMed2006

Comparison of coronary calcium and stress myocardial perfusion imaging in apparently healthy siblings of individuals with premature coronary artery disease.

Detection of subclinical coronary atherosclerosis is possible using exercise myocardial perfusion imaging for inducible ischemia or multidetector computed tomography for coronary artery calcium (CAC), which is used to detect subclinical coronary atherosclerosis. The extent to which these screening tests converge in an asymptomatic population that is at increased risk for coronary artery disease remains unknown. We compared the concordance of findings in 260 asymptomatic middle-age siblings of hospitalized index patients <60 years of age with documented coronary artery disease. All subjects underwent maximal exercise testing with postexercise and delayed attenuation-corrected thallium single-photon emission computed tomography and multidetector computed tomography for CAC. An abnormal exercise single-photon emission computed tomographic (SPECT) result occurred in >50% of subjects with a CAC score >100, but also in 12% with no CAC, 9% with CAC scores of 1 to 10, and 20% with CAC scores of 11 to 100. In subjects with an abnormal exercise SPECT result, 59% had CAC scores < or =100. Overall, there was only a modest agreement between an abnormal exercise SPECT result and high CAC scores. In conclusion, although moderate or severe CAC is often associated with inducible ischemia, the absence of CAC or the presence of only mild CAC by no means precludes inducible myocardial ischemia. These screening tests may reflect different aspects or stages of coronary disease in an asymptomatic middle-age population.

Adult↗
PubMed2006

Association of body mass index, metabolic syndrome, and leukocyte count.

Obesity and metabolic syndrome (MS), which often co-exist, are associated with an increased cardiovascular risk. An increased leukocyte count is also associated with an increased cardiovascular risk. However, the role of obesity, independent of MS, has been debated. We sought to assess the influence of MS on the association of obesity and leukocyte count in asymptomatic patients. The data from 431 asymptomatic Brazilian men (mean age 46 +/- 7 years), who presented for cardiovascular risk assessment, were analyzed. MS was defined as the presence of > or =3 of the following risk factors: hypertension (> or =130/85 mm Hg), truncal obesity (> or =102 cm or 40 in), hypertriglyceridemia (> or =150 mg/dl), high-density lipoprotein cholesterol (< or =40 mg/dl), and hyperglycemia (glucose > or =110 mg/dl). Obesity was defined as a body mass index of > or =30 kg/m(2). Confounding variables (age, smoking, lipid-lowering therapy, and physical activity) and leukocyte count (10(9)/L) were recorded. The patients were divided into 4 groups: group1, no obesity and no MS; group 2, obesity but no MS; group 3, no obesity but MS; and group 4, obesity and MS. The mean leukocyte count increased from groups 1 to 4 (6.10 +/- 0.09, 6.42 +/- 0.28, 6.71 +/- 0.21, and 6.96 +/- 0.22 x 10(9)/L, p < 0.001 for trend). Multivariate regression analysis demonstrated that the leukocyte count was significantly higher in groups 3 (coefficient 0.61, p = 0.007) and 4 (coefficient 0.86, p < 0.001) compared with group 1. However, no significant difference was found in the leukocyte count between groups 1 and 2 (coefficient 0.29, p = 0.42) and groups 3 and 4 (coefficient 0.25, p = 0.41). The association between obesity and leukocyte count was highly dependent on the presence of MS.

Body Mass Index↗
PubMed2006

Primary prevention for patients with intermediate Framingham risk scores.

Coronary heart disease (CHD) is the leading cause of mortality in the industrialized world. Proper identification of individuals at risk for CHD is challenging. The Framingham Risk Score, the most widely accepted tool for quantifying 10-year risk, fails to identify a great proportion of future CHD. Because of the health and economic consequences of CHD, there is a need to develop better prognostic tools for primary prevention. Coronary artery calcium scoring, C-reactive protein measurement, and heart rate recovery and exercise tolerance during exercise stress test may be useful tools for better risk stratification of intermediate-risk patients.

C-Reactive Protein↗
PubMed2006

Reproducibility of CT measurements of aortic valve calcification, mitral annulus calcification, and aortic wall calcification in the multi-ethnic study of atherosclerosis.

RATIONALE AND OBJECTIVES: Extracoronary calcifications may have clinical significance. The error in extracoronary calcification measurements is still unknown. Accurate quantification of calcifications of the aortic valve (AVC), mitral annulus (MAC), and aortic wall (AWC) may be possible by using cardiac computed tomography (CT). We sought to establish the interscan, interobserver, and intraobserver reproducibility of these measures in all cardiac CT scans in the Multi-Ethnic Study of Atherosclerosis. MATERIALS AND METHODS: We measured extracoronary calcifications in 100 randomly selected participants to assess interobserver, interscan, and intraobserver variability. Two scans were available for analysis in 99 of these participants, and we quantified thoracic aorta and valvular calcifications. RESULTS: Mean interscan variability of AVC was 9.7% +/- 11.4% and 8% +/- 10.3% for Agatston and volume scores, with variability of the median at 6.4% and 5.5%, respectively (P > .05). MAC inter-reader variability was 8.2% and 8.9%, with interscan variability of 28% and 33% and intrareader variability of 4% and 4.1%, respectively. For AWC, inter-reader variability was 3%-7.1%, interscan variability was 17%-18%, and intrareader variability was 0.4%-1.4%. CONCLUSION: AVC, MAC, and AWC measurements are sufficiently reproducible to allow serial investigations over a time suitable for clinical studies.

Aged↗
PubMed2006

Gender and C-reactive protein: data from the Multiethnic Study of Atherosclerosis (MESA) cohort.

BACKGROUND: American Heart Association/Centers for Disease Control and Prevention guidelines support the measurement of C-reactive protein (CRP) to further risk stratify individuals at intermediate risk (10%-20% 10-year risk) for heart disease. Determining gender-specific differences in CRP may alter how CRP levels are interpreted and used to determine risk. METHODS: MESA is a prospective cohort consisting of 6814 men and women aged 45 to 84 years recruited from 6 US communities. Nonparametric analyses were performed to determine differences in CRP levels by gender in the entire cohort and after stratifying by use of estrogen medication (n = 944). Stratifying by median body mass index (BMI) and generalized linear models were also used to account for confounding variables associated with CRP. RESULTS: Overall, women had substantially higher median CRP levels compared with men (2.56 vs 1.43 mg/L, P < .0001). After excluding women using estrogen and individuals with CRP >10 mg/L, median CRP levels remained higher in women compared with men (1.85 vs 1.33 mg/L, P < .0001). When participants were stratified into high and low BMI groups, the gender difference in CRP levels remained. This pattern of higher CRP levels in women was consistent across all ethnic subgroups even after multivariable adjustment. CONCLUSIONS: C-reactive protein levels were higher in women compared with men despite accounting for BMI and other common confounding variables. This gender difference was maintained across all ethnic subgroups. These results suggest that evaluation of gender-specific CRP cut points to determine cardiovascular risk should be considered.

Black or African American↗
PubMed2006

Subclinical coronary atherosclerosis: racial profiling is necessary!

OBJECTIVES: We aim to review the studies comparing coronary calcification across different ethnic groups. BACKGROUND: There is still uncertainty regarding ethnic differences in the prevalence, progression, and risk of coronary artery disease. Clues to possible racial differences in rates of coronary heart disease (CHD) may be found by identifying subclinical disease. Coronary artery calcification (CAC) can be used to predict risk of CHD in both symptomatic and asymptomatic subjects. METHODS: Online databases were searched for studies assessing racial differences in CAC. RESULTS: Most of the published studies have shown that racial differences exist in the prevalence and severity of CAC. Whites have a higher prevalence of CAC as compared to African Americans and other ethnic groups even after adjustment for risk factors. These differences in CAC are even more pronounced in men and in the elderly. Data regarding the distribution of CAC in ethnic groups outside the United States are limited. Emerging evidence indicates that while several ethnic groups outside the United States tend to have a greater prevalence of CHD risk factors, their prevalence of CAC is lower, as compared with Americans. Thus, the data obtained in the United States may not be able to be fully extrapolated to populations outside the United States for assessment of CHD risk. CONCLUSIONS: The presence and extent of CAC varies among different racial groups within and outside the United States. The relationship between calcification and the incidence of CHD in these ethnic groups needs further exploration. Thus, it is important to develop ethnic specific CAC nomograms to more accurately determine the underlying CHD risk associated with CAC in these individuals. It will also be imperative to obtain outcome data and relate it to baseline levels of CAC to help us put in perspective the significance of racial differences in CAC and how they impact on cardiac risk prediction.

Adult↗
PubMed2006

Association of increased cardiorespiratory fitness with low risk for clustering of metabolic syndrome components in asymptomatic men.

BACKGROUND: From a preventive aspect, it is especially important to investigate the lifestyle risk factors associated with cardiovascular disease (CVD). The purpose of this study was to determine the relationship of increasing metabolic syndrome (MS) components across increasing levels of estimated cardiorespiratory fitness (CRF) in asymptomatic young to middle-aged men. METHODS: We studied 449 consecutive asymptomatic men (47 +/- 7 years) who underwent a maximal treadmill exercise test according to the Bruce protocol. Cardiorespiratory fitness (CRF) was divided into tertiles based on metabolic equivalents (METs). The following MS components were studied: 1) waist circumference > 102 cm; 2) serum triglycerides > or = 150 mg/dL; 3) HDL cholesterol levels of < 40 mg/dL; 4) fasting blood glucose (FBG) > or = 110 mg/dL or 5) blood pressure > or = 130/85 mmHg or treated hypertension. Multinomial logistic regression was used to investigate the relationship between clustering of MS components and CRF as determined by metabolic equivalents (METs). We used polytomous logistic regression to determine the likelihood of clustering of increasing components of metabolic syndrome with intermediate (2nd tertile) and low (1st tertile) levels of CRF as compared to those with highest levels of CRF (3rd tertile). RESULTS: Overall in the study population, zero, 1, 2 and > or = 3 (i.e., metabolic syndrome) risk factors for MS were observed in 29% (n = 129), 26% (n = 118), 22% (n = 98) and 23% (n = 104) men, respectively. The mean METS achieved in the study population was 10 +/- 2 (range 4-20). Nearly half (49%) of individuals with the highest levels of CRF had no MS risk factors whereas only 18% of those with low CRF (METS < 9) had no MS risk factors. On the other end of the spectrum, the prevalence of MS (> or = 3 MS risk factors) increased significantly across decreasing levels of CRF (6, 22, 33% p < 0.0001 for trend). Multivariable polytomous logistic regression (adjusting for age, smoking, cholesterol-lowering therapy) demonstrated that individuals with low CRF (1st tertile of METS) compared to those with highest CRF had 3.1- (p = 0.001) and 11.8- (p < 0.0001) fold higher risk of having 2 and > or = 3 MS components, respectively. Similar results were observed when the analyses was repeated adjusting for Framingham risk score. CONCLUSIONS: Asymptomatic men with low levels of CRF have a greater likelihood for clustering of MS components and thus are at higher CVD risk. Further studies are needed to define the risk of cardiovascular disease in patients with intermediate levels of CRF and address which treatment strategies are most important given an individual's risk profile.

Adult↗
PubMed2006

Framingham risk equation underestimates subclinical atherosclerosis risk in asymptomatic women.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among American women. Currently, global risk assessment derived by Framingham risk equation (FRE) is used to identify women at increased risk for CHD. Electron-beam computed tomography (EBCT) derived coronary artery calcium (CAC) scores are validated markers for future CHD events among asymptomatic individuals. However, the adequacy of FRE for identifying asymptomatic women with CAC is unknown. METHODS AND RESULTS: We studied 2447 consecutive non-diabetic asymptomatic females (55 +/- 10 years). Based upon FRE, 90% were classified as low-risk (FRE < or = 9% 10-year risk of hard CHD events), 10% intermediate-risk (10-20%), and none were considered as high-risk (> 20%). Coronary artery calcium was present in 33%, whereas CAC > or = 100 and CAC > or = 400 were seen in 10 and 3% of women, respectively. Overall, 20% of women had age-gender derived > or = 75th percentile CAC. According to FRE, the majority (84%) of women with significant CAC > or = 75th percentile were classified as low-risk. Approximately half (45%) of low-risk women with > or = 2 CHD risk factors and a family history of premature CHD had significant CAC. CONCLUSION: Framingham risk equation frequently classifies women as being low-risk, even in the presence of significant CAC. Determination of CAC may provide incremental value to FRE in identifying asymptomatic women who will benefit from targeted preventative measures.

Atherosclerosis↗
PubMed2006

Therapy Insight: managing cardiovascular risk in patients with rheumatoid arthritis.

Chronic low-grade inflammation was recognized during the past decade as an important risk factor for the development of atherosclerosis and, more recently, for the development of heart failure. Patients with rheumatoid arthritis (RA) are at increased risk of morbidity and mortality from ischemic cardiovascular events and heart failure. Epidemiologic and clinical studies indicate that RA is an independent risk factor for cardiovascular disease, which suggests that chronic exposure to high levels of inflammatory mediators contributes to this enhanced risk. The relative contribution of conventional risk factors to the acceleration of cardiovascular disease does not seem to be increased in patients with RA compared with control populations. Nonetheless, some preclinical laboratory measures of risk factors (e.g. insulin sensitivity) are adversely modulated in the context of the highly inflammatory rheumatoid microenvironment. Discerning the net effect of RA therapies on cardiovascular disease is also challenging because, theoretically, their biologic effects could either promote or attenuate atherosclerosis and ventricular dysfunction; however, available data suggest a beneficial effect on cardiovascular morbidity and mortality in patients with RA. This review provides an overview of the potential influence of RA and its treatment on the development and progression of cardiovascular disease, and outlines some preliminary recommendations for prevention and management of this complication in patients with RA.

Antirheumatic Agents↗