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Biomedical subjects

R S Blumenthal

Publications and source records attributed to R S Blumenthal.

At least 19 recordsLinked to original sources

Association of white blood cell count with systolic blood pressure within the normotensive range.

Hypertension and inflammation promote cardiovascular disease (CVD). Even high normal systolic blood pressure (SBP) is associated with increased CVD risk. We assessed the relationship of elevated SBP within the normotensive range and white blood cell (WBC) count. This is a cross-sectional study of 3484 white asymptomatic individuals (mean age: 43+/-8 years, 79% males) without hypertension with SBP<140 mm Hg. White blood cell count >or=75th percentile (8.35 x 10(9) cells/l) was considered cutoff for elevated WBC. Subjects were classified into three levels of SBP (first: <120 mm Hg, n=1,176, 34%; second: 120-129 mm Hg, n=1,654, 47%; third: 130-139 mm Hg, n=654, 19%). Mean WBC count increased linearly across SBP categories (first: 6.14+/-1.54, second: 6.20+/-1.52, third: 6.41+/-1.62, P=0.02 for trend). There was a linear increase in prevalence of elevated WBC across higher SBP categories (22, 24 and 28%, P=0.02). As compared to those with SBP<120 mm Hg, in multivariate linear regression analyses (adjusting for age, gender, smoking status, diabetes, body mass index, physical activity, cholesterol/high-density lipoprotein cholesterol ratio) WBC count was significantly higher among participants with SBP 130-139 mm Hg (regression coefficient: 2.64, 95% confidence interval: 1.04-4.24, P=0.001). Odds ratio for prevalence of elevated WBC with SBP<120 mm Hg as reference group was 1.14 (0.92-1.41) for SBP 120-129 mm Hg and 1.50 (1.15-1.92) for SBP 130-139 mm Hg. In conclusion, Higher SBP within the normotensive range is also associated with elevated WBC count. Further studies are needed to clarify the role of inflammation in high normal SBP and associated CVD risk.

Adult↗

Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality.

BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) contains all known and potential atherogenic lipid particles. Therefore, non-HDL-C level may be as good a potential predictor of risk for cardiovascular disease (CVD) as low-density lipoprotein cholesterol (LDL-C). OBJECTIVES: To determine whether non-HDL-C level could be useful in predicting CVD mortality and to compare the predictive value of non-HDL-C and LDL-C levels. METHODS: Data are from the Lipid Research Clinics Program Follow-up Study, a mortality study with baseline data gathered from 1972 through 1976, and mortality ascertained through 1995. A total of 2406 men and 2056 women aged 40 to 64 years at entry were observed for an average of 19 years, with CVD death as the main outcome measure. RESULTS: A total of 234 CVD deaths in men and 113 CVD deaths in women occurred during follow-up. Levels of HDL-C and non-HDL-C at baseline were significant and strong predictors of CVD death in both sexes. In contrast, LDL-C level was a somewhat weaker predictor of CVD death in both. Differences of 0.78 mmol/L (30 mg/dL) in non-HDL-C and LDL-C levels corresponded to increases in CVD risk of 19% and 15%, respectively, in men. In women, differences of 0.78 mmol/L (30 mg/dL) in non-HDL-C and LDL-C levels corresponded to increases in CVD risk of 11% and 8%, respectively. CONCLUSIONS: Non-HDL-C level is a somewhat better predictor of CVD mortality than LDL-C level. Screening for non-HDL-C level may be useful for CVD risk assessment.

Adult↗

Dietary Counseling for High Blood Cholesterol in Families at Risk of Coronary Disease.

A positive family history of coronary heart disease alone confers an increased risk, which may be affected by untreated hypercholesterolemia. Dietary counseling is a first-line treatment approach. To determine whether nurse counseling can provide additional benefits over usual physician efforts to lower dietary fat in high-risk persons, 117 apparently healthy adult siblings of persons with premature coronary heart disease were counseled by a registered nurse using adapted national guidelines. Reductions in total fat, saturated fat, and cholesterol were significantly greater in the nurse group compared to those in the usual care group. Total fat intake decreased by 14 g in the nurse group, compared with an increase of 5 g in the usual care group (p=0.0001). Assignment to the nurse group was also a significant predictor of a greater reduction in the percentage of total fat calories (p=0.008). The authors conclude that a registered nurse may serve as a complement to usual care in efforts to lower dietary fat and cholesterol in high-risk families. (c)2001 CHF, Inc.

Journal Article↗

Lipid disorders: justification of methods and goals of treatment.

Dyslipidemia is a major risk factor for coronary heart disease (CHD). While some uncertainty exists about the clinical significance of improving high-density lipoprotein cholesterol and triglyceride levels, large primary- and secondary-prevention studies aimed at lowering low-density lipoprotein cholesterol levels with statins have convincingly reduced CHD events and total mortality. Despite the strong clinical evidence and widely publicized treatment guidelines, many hyperlipidemic patients receive inadequate lipid-lowering treatment. This failure to achieve clinical treatment goals may be due to poor physician adherence to treatment guidelines, patient noncompliance, and the presence of concomitant medical conditions that modify typical hyperlipidemia management. This review considers the challenges and available strategies to optimize lipid management in patients at risk for CHD.

Adult↗

Statins: effective antiatherosclerotic therapy.

BACKGROUND: Statins are the most effective agents currently available for lowering plasma levels of low-density lipoprotein cholesterol (LDL-C) and are the mainstay of therapy for hyperlipidemia. The statins are highly liver-selective, inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a key enzyme in the synthesis of cholesterol. Several large, controlled clinical trials have confirmed significant reductions in rates of coronary heart disease morbidity and death with long-term statin therapy in patients with mild to severe hypercholesterolemia. METHODS AND RESULTS: This review article is based on a literature search of more than 60 relevant articles from peer-reviewed journals. Search engines included Medline and Embase. In surveying clinical and angiographic evidence, we found that statins appear to reduce the incidence of coronary events by slowing the progression of atherosclerosis and preventing atheromatous lesion formation. We found that the 6 statins currently marketed-atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin-differ in their inhibitory action on the HMG-CoA reductase enzyme. CONCLUSIONS: The use of more potent statins such as atorvastatin and simvastatin affords greater lowering of LDL-C and triglyceride levels, allowing more patients to achieve target goals. The question of how low LDL-C levels should be lowered will be answered by ongoing clinical trials.

Anticholesteremic Agents↗

Medical therapy versus coronary angioplasty in stable coronary artery disease: a critical review of the literature.

The recent publication of the Atorvastatin Versus Revascularization Treatment (AVERT) trial has renewed debate on the optimal management strategy for relatively stable patients with coronary artery disease. Currently, coronary angiography and percutaneous coronary intervention are often performed in stable patients with good exercise tolerance who have not been treated with proven medications such as aspirin, statins and beta-adrenergic blocking agents in conjunction with comprehensive lifestyle modification. We review the results of prior trials comparing medical therapy with angioplasty and assess their strengths and limitations and then make conclusions about the aggregate data. Next, we describe the ongoing Clinical Outcome Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, which will be the largest of the studies comparing optimal medical therapy and percutaneous revascularization. This study will employ intensive medical management in all patients with coronary disease, and the incremental benefit of state of the art revascularization techniques in terms of clinical event reduction, quality of life issues and cost-effectiveness will be addressed. For now, aggressive medical therapy and revascularization should be viewed as complementary rather than opposing strategies. All patients with coronary heart disease should receive proven medical and lifestyle prescriptions to favorably alter the atherosclerotic process. Percutaneous revascularization without comprehensive risk factor modification is a suboptimal therapeutic strategy.

Angioplasty, Balloon, Coronary↗

Spot urinary albumin-creatinine ratio predicts left ventricular hypertrophy in young hypertensive African-American men.

Hypertensive patients with target organ damage are at increased cardiovascular risk, and should be treated most aggressively. The association between urinary albumin excretion and left ventricular hypertrophy (LVH) in prior studies is inconsistent, and has not been described using a single, random spot urine specimen. Therefore, we evaluated the association between the urinary albumin creatinine ratio (ACR) and left ventricular (LV) mass and also tested the hypothesis that a simple random, single-void urine ACR would identify high risk young, hypertensive, African-American men. We measured echocardiographic LV mass and a random spot urinary ACR in 109 untreated, hypertensive, young, inner city, African-American men. The mean age was 41 +/- 6 years and the mean blood pressure (BP) was 157 +/- 19/107 +/- 13 mm Hg. Microalbuminuria (ACR 30 to 300 mg/g) was present in 22% of subjects. The ACR is higher in the men with LVH than in the men without LVH (P < .05). Increased ACR is a predictor of increased LV mass index (P < .003) using multiple linear regression. An ACR >30 mg/g has a sensitivity of 33% and a specificity of 82% for the diagnosis of echocardiographic LVH. In conclusion, elevated random spot ACR is a marker of increased LV mass, independent of BP, in young urban African-American men with hypertension, and may help to determine the aggressiveness of antihypertensive therapy in this high-risk group.

Adolescent↗

Correlates of high HDL cholesterol among women with coronary heart disease.

BACKGROUND: The National Cholesterol Education Program (NCEP) has designated high-density lipoprotein cholesterol (HDL-C) > or =60 mg/dL a "negative" coronary heart disease (CHD) risk factor, but a substantial proportion of coronary events occur among women despite high HDL-C levels. METHODS AND RESULTS: The objective of this study was to characterize postmenopausal women with prevalent CHD despite HDL-C > or =60 mg/dL and to identify factors that may attenuate the protective effect of high HDL-C. We analyzed baseline data from a randomized, double-blind study of estrogen/progestin replacement therapy in 2763 postmenopausal women <80 years old with CHD. Demographics, CHD risk factors, medications, anthropometrics, and lipid levels were compared among women with low, normal, and high HDL-C by NCEP criteria with and without stratification by use of lipid-lowering medications. Independent correlates of high HDL-C were determined by logistic regression analysis. HDL-C > or =60 mg/dL was present in 20% of participants. Women with high HDL-C were older, better educated, had fewer CHD risk factors, lower triglyceride levels and total cholesterol/HDL-C ratio, and were more likely to report past estrogen and current calcium antagonist, niacin, and statin use. beta-Blocker, diuretic, and fibrate use was less common. Older age, alcohol consumption, niacin, and calcium antagonist use and prior estrogen use were independently associated with high HDL-C, whereas waist-to-hip ratio, smoking, triglyceride level, and beta-blocker and fibrate use were inversely associated (all P <.05). CONCLUSIONS: High HDL-C, as defined by the NCEP, occurred in 20% of women with CHD in this cohort without a concomitantly higher prevalence of other CHD risk factors. Redefinition of "high" HDL-C levels for women may be warranted.

Adult↗

Glitazones and the potential improvement of lipid profiles in diabetes patients at high risk for cardiovascular disease.

Most deaths and hospitalizations in patients with diabetes are related to atherosclerotic vascular disease. An asymptomatic patient with type 2 diabetes has a cardiovascular risk comparable to that of a patient without diabetes who has a history of a myocardial infarction. The American Heart Association classifies diabetes as a coronary heart disease risk equivalent. Thus, it is important in patients with diabetes to aim for systolic blood pressures less than 130 mm Hg, using an angiotensin-converting enzyme inhibitor-based regimen. The target hemoglobin A1C (HbA1C) for those patients is < 7%. New oral insulin-sensitizing medications, known as thiazolidinediones or glitazones, are useful to improve glycemic control. Most patients with diabetes require 2 or more oral agents to achieve optimal glucose control. Glitazones generally lower HbA1C by 1% to 2%. They also raise high-density lipoprotein cholesterol levels and lower triglycerides. Thus, they may potentially improve low-density lipoprotein (LDL) particle sizes by converting small, dense LDL particles into larger, less atherogenic ones. Current data concerning the lipid effects of pioglitazone and rosiglitazone are reviewed in this article.

Coronary Disease↗

Higher prevalence of GPIIIa PlA2 polymorphism in siblings of patients with premature coronary heart disease.

BACKGROUND: The Pl(A2) polymorphism of GPIIIa has been associated with unstable coronary syndromes in some studies, but the association has remained debated. None of the previous studies have focused on families at high risk. Risk factors tend to cluster within kindreds with high prevalence of premature coronary heart disease (CHD). Therefore, a heightened prevalence of the Pl(A2) polymorphism among siblings of patients with CHD would support the hypothesis that Pl(A2) is linked, directly or indirectly, to CHD. OBJECTIVES: To measure the prevalence of the Pl(A2) polymorphism among siblings of patients with CHD before the age of 60 years and to seek an association between the Pl(A2) polymorphism and established atherosclerotic and thrombogenic risk factors. METHODS: From January 1994 to April 1996, we genotyped 116 asymptomatic siblings (60 Caucasians, 56 Afro-Caribbeans) of patients with CHD manifestations before the age of 60 years for the Pl(A) polymorphism (also called HPA-1). A control cohort was used for comparison, consisting of individuals that were matched for race and geographic area but were free of CHD (n = 268, 168 Caucasians and 100 Afro-Caribbeans). In addition, we have characterized the sibling cohort for other atherogenic and thrombogenic risk factors. RESULTS: The prevalence of Pl(A2)-positive individuals (Pl(A2)[+], Pl(A1/A2) heterozygotes plus Pl(A2/A2) homozygotes) in the sibling cohort was high: 41.4%. When analyzed separately, the prevalence of Pl(A2)(+) siblings was 53.3% among Caucasians and 28.6% among Afro-Caribbeans. There was no association between Pl(A2) and other established atherogenic or thrombogenic risk factors. Interestingly, the clustering of other risk factors was lesser among Pl(A2)(+) siblings than their Pl(A1) counterparts. CONCLUSIONS: This study supports the hypothesis that the prevalence of Pl(A2)(+) individuals is high in kindreds with premature CHD. Hence, like the established risk factors that tend to cluster in families with premature CHD and contribute strongly to the accelerated atherosclerotic process affecting these individuals, the Pl(A2) polymorphism of GPIIIa may represent an inherited risk that promotes the thromboembolic complications of CHD. That these asymptomatic Pl(A2)(+) siblings had overall less established risk factors than their Pl(A1) counterparts might represent an explanation for why they remained asymptomatic despite their Pl(A2) positivity.

Adult↗

Markedly high prevalence of coronary risk factors in apparently healthy African-American and white siblings of persons with premature coronary heart disease.

Among persons with a family history of premature coronary heart disease (CHD), siblings bear an excess risk of CHD that is as high as 12 times that of the general population. Aggressive, new, national guidelines for CHD risk reduction have focused on high-risk families, yet little is known about actual remediable risk factors in siblings of persons with premature CHD. To determine the magnitude of the problem relative to the general population, we screened 846 unaffected siblings (ages 30 to 59 years) of persons with documented CHD before age 60 years and compared their risk factor values with population reference norms obtained in the Third National Health and Nutrition Examination Survey (NHANES III) and the National Health Interview Survey (NHIS). Mean levels of low-density lipoprotein cholesterol were 0.52 mmol/L (20 mg/dl) higher in siblings; the prevalence of low-density lipoprotein cholesterol > or =4.14 mmol/L (160 mg/dl) was nearly twice that of race, sex, and age-specific values from NHANES III. Levels of high-density lipoprotein cholesterol <0.91 mmol/L (35 mg/dl) were similar between siblings and NHANES III (11% and 12%, respectively). Only 4% of all siblings had triglyceride levels > or =4.52 mmol/L (400 mg/dl). Hypertension prevalence was twice as high among siblings as among the NHANES III. Current smoking was 33.9% in white siblings and 25.5% in the NHIS, whereas smoking in African-Americans was similar to that in the NHIS (31.1% vs 29.2%). A mere 13% to 29% of siblings were without any major remediable risk factors. The overwhelming need for risk factor modification in this easily identifiable high-risk population supports aggressive national guidelines and demonstrates the lack of adequate treatment of apparently healthy siblings of persons with premature CHD.

Adult↗

Nurse-mediated cholesterol management compared with enhanced primary care in siblings of individuals with premature coronary disease.

BACKGROUND: Siblings of individuals with premature coronary heart disease have a high prevalence of low-density lipoprotein cholesterol (LDL-C) levels requiring treatment. OBJECTIVE: To evaluate management strategies for high LDL-C levels in apparently healthy 30- to 59-year-old siblings of individuals with documented coronary heart disease prior to age 60 years. METHODS: In a 2-year trial of care provided by either a nurse trained in lipid management (NURS) or enhanced primary care (EPC), in which physicians received recommendations based on national guidelines, 156 siblings with LDL-C levels of 4.14 mmol/L (160 mg/dL) were randomized by family. The LDL-C goal levels below 3.36 mmol/L (130 mg/dL) were compared between and within intervention groups. Multiple logistic regression analyses were applied to predict 2-year achievement of the goal. RESULTS: The NURS group achieved a significantly greater percentage of goal LDL-C levels than the EPC group (26% vs 10%; P=.008). The NURS LDL-C levels decreased an average of 0.91 mmol/L (35 mg/dL) while EPC levels decreased by 0.52 mmol/L (24 mg/dL) (P=.09). In the final multivariate model, siblings taking lipid-lowering drug treatment were 6.02 times more likely (95% confidence interval, 2.24-16.18) than those not receiving pharmacotherapy to achieve LDL-C goals; nurse management (P=.09) was marginally significant. Pharmacotherapy was instituted in 45.2% of NURS and 16.7% of EPC siblings (P=.001). CONCLUSIONS: High LDL-C levels in siblings were more effectively treated by a trained nurse, probably related to greater adherence to the application of national guidelines. Nonetheless, the majority of siblings with high LDL-C levels did not meet goal levels 2 years after an index case coronary heart disease event.

Adult↗

Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction.

BACKGROUND: The extent of microvascular obstruction during acute coronary occlusion may determine the eventual magnitude of myocardial damage and thus, patient prognosis after infarction. By contrast-enhanced MRI, regions of profound microvascular obstruction at the infarct core are hypoenhanced and correspond to greater myocardial damage acutely. We investigated whether profound microvascular obstruction after infarction predicts 2-year cardiovascular morbidity and mortality. METHODS AND RESULTS: Forty-four patients underwent MRI 10 +/- 6 days after infarction. Microvascular obstruction was defined as hypoenhancement seen 1 to 2 minutes after contrast injection. Infarct size was assessed as percent left ventricular mass hyperenhanced 5 to 10 minutes after contrast. Patients were followed clinically for 16 +/- 5 months. Seventeen patients returned 6 months after infarction for repeat MRI. Patients with microvascular obstruction (n = 11) had more cardiovascular events than those without (45% versus 9%; P=.016). In fact, microvascular status predicted occurrence of cardiovascular complications (chi2 = 6.46, P<.01). The risk of adverse events increased with infarct extent (30%, 43%, and 71% for small [n = 10], midsized [n = 14], and large [n = 14] infarcts, P<.05). Even after infarct size was controlled for, the presence of microvascular obstruction remained a prognostic marker of postinfarction complications (chi2 = 5.17, P<.05). Among those returning for follow-up imaging, the presence of microvascular obstruction was associated with fibrous scar formation (chi2 = 10.0, P<.01) and left ventricular remodeling (P<.05). CONCLUSIONS: After infarction, MRI-determined microvascular obstruction predicts more frequent cardiovascular complications. In addition, infarct size determined by MRI also relates directly to long-term prognosis in patients with acute myocardial infarction. Moreover, microvascular status remains a strong prognostic marker even after control for infarct size.

Aged↗

Risk factors in the offspring of women with premature coronary heart disease.

Some studies suggest that first-degree relatives of female patients with premature coronary heart disease (CHD) are at greater risk for early disease than if the proband is a male patient. To examine coronary risk factors, related knowledge, attitudes, and beliefs concerning CHD risk, we screened a sample of 87 apparently healthy offspring (56 female subjects and 31 male subjects) of women with documented premature CHD. More than half of the offspring had total and low-density lipoprotein cholesterol levels above the recommended levels for primary prevention, 31% were current smokers, and 56% exercised fewer than three times a week. A high proportion were overweight with a high prevalence of central obesity. A total of 13% had only one major risk factor, a family history of premature CHD, 10% had two risk factors, 23% had three, and 54% had four or more CHD risk factors. When compared with the Framingham cohort, 29% of sons and 30% of daughters exceeded their age- and sex-specific average risk for having CHD in 10 years. Only 28% identified heredity as a major cause of CHD, and 47% perceived their risk for future myocardial infarction as less than or equal to that of others their age. These findings suggest that adult children of women with premature CHD have a high prevalence of modifiable risk factors and do not perceive themselves to be at risk for CHD.

Adult↗