bluuebunny/crossref_metadata_2025 huggingface dataset:
NSCL‐1 and ‐2 control the formation of precerebellar nuclei by orchestrating the migration of neuronal precursor cells
Authors: Schmid Thomas , Krüger Marcus , Braun Thomas
Published: June 2007

During embryonic development post‐mitotic neurons of the precerebellar neuroepithelium, migrate from the rhombic lip to the ventral part of the neural tube to form the precerebellar nuclei of the pons and medulla oblongata. In this study, we show that neural basic helix‐loop‐helix transcription factors NSCL‐1 and ‐2 are expressed in all cells of the anterior extramural migration stream (aes), which forms the precerebellar nuclei. The combined inactivation of NSCL‐1 and ‐2 led to a complete absence of the pontine nuclei and a strong reduction in the reticulotegmental nuclei. We demonstrate that NSCL‐1/2 were required for a sustained expression of the netrin receptor and cell guidance molecule Dcc in the aes. Unc5H3, a second netrin receptor, which serves as a stop signal for migratory cells was up‐regulated in NSCL‐1/2 deficient cells, which ceased migration and accumulated ectopically. Furthermore, we observed a massive increase of apoptosis in cells of the aes in the absence of NSCL‐1/2, which together with the arrest of migration might explain the virtually complete loss of aes‐derived structures in NSCL‐1/2 mutant mice. We conclude that NSCL‐1/2 maintain migration and survival of cells in the aes.
Activation of extracellular signal‐regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation
Authors: Katsura Hirokazu , Obata Koichi , Mizushima Toshiyuki , Sakurai Jun , Kobayashi Kimiko , Yamanaka Hiroki , Dai Yi , Fukuoka Tetsuo , Sakagami Masafumi , Noguchi Koichi
Published: June 2007

Heat and cold hyperalgesia is a common feature of inflammatory pain. To investigate whether activation of extracellular signal‐regulated protein kinase 5 (ERK5), also known as big mitogen‐activated protein kinase 1, in primary sensory neurons participates in inflammatory pain, we examined the phosphorylation of ERK5 in the dorsal root ganglion (DRG) after peripheral inflammation. Inflammation induced by complete Freund’s adjuvant produced heat and cold hyperalgesia on the ipsilateral hind paw and induced an increase in the phosphorylation of ERK5, mainly in tyrosine kinase A‐expressing small‐ and medium‐size neurons. In contrast, there was no change in ERK5 phosphorylation in the spinal dorsal horn. ERK5 antisense, but not mismatch, oligodeoxynucleotide decreased the activation of ERK5 and suppressed inflammation‐induced heat and cold hyperalgesia. Furthermore, the inhibition of ERK5 blocked the induction of transient receptor potential channel TRPV1 and TRPA1 expression in DRG neurons after peripheral inflammation. Our results show that ERK5 activated in DRG neurons contribute to the development of inflammatory pain. Thus, blocking ERK5 signaling in sensory neurons that has the potential for preventing pain after inflammation.
Nicotinic α5 subunit deletion locally reduces high‐affinity agonist activation without altering nicotinic receptor numbers
Authors: Brown Robert W. B. , Collins Allan C. , Lindstrom Jon M. , Whiteaker Paul
Published: June 2007

Neuronal nicotinic acetylcholine receptor subunit α5 mRNA is widely expressed in the CNS. An α5 gene polymorphism has been implicated in behavioral differences between mouse strains, and α5‐null mutation induces profound changes in mouse acute responses to nicotine. In this study, we have examined the distribution and prevalence of α5* nicotinic acetylcholine receptor in mouse brain, and quantified the effects of α5‐null mutation on pre‐synaptic nicotinic acetylcholine receptor function (measured using synaptosomal86Rb+efflux) and overall [125I]epibatidine binding site expression. α5* nicotinic acetylcholine receptor expression was found in nine of fifteen regions examined, although < 20% of the total nicotinic acetylcholine receptor population in any region contained α5. Deletion of the α5 subunit gene resulted in localized loss of function (thalamus, striatum), which was itself confined to the DHβE‐sensitive receptor population. No changes in receptor expression were seen. Consequently, functional changes must occur as a result of altered function per unit of receptor. The selective depletion of high agonist activation affinity sites results in overall nicotinic function being reduced, and increases the overall agonist activation affinity. Together, these results describe the receptor‐level changes underlying altered behavioral responses to nicotine in nicotinic acetylcholine receptor α5 subunit‐null mutants.
Differential ability of a thiazolidinedione PPARγ agonist to attenuate cytokine secretion in primary microglia and macrophage‐like cells
Authors: Woster Andrew P. , Combs Colin K.
Published: June 2007

Peroxisome proliferator‐activated receptor gamma (PPARγ) agonists are known to inhibit select pro‐inflammatory changes in models of CNS and systemic inflammation. Recent reports suggest that these anti‐inflammatory effects are due to mechanisms other than canonical nuclear receptor‐mediated transcriptional alteration. Using primary microglia and the monocytic cell line, THP‐1, we demonstrate that rosiglitazone, a PPARγ‐activating thiazolidinedione, decreases pro‐inflammatory cytokine secretion as measured by ELISA. Cells were pre‐treated with various thiazolidinediones, including rosiglitazone, prior to stimulation with lipopolysaccharide or phorbol 12‐myristate 13‐acetate (PMA) to stimulate cytokine production. Tumor necrosis factor alpha (TNFα) secretion was significantly inhibited in both primary microglia and THP‐1 cells differentiated for 72 h in the presence of PMA to induce a macrophage‐like phenotype. No reduction in TNFα secretion was observed in undifferentiated THP‐1 cells with rosiglitazone pre‐treatment. Electrophoretic mobility shift assay revealed no significant difference in PPARγ activation between PMA‐differentiated and undifferentiated THP‐1 cells. When PMA‐differentiated and undifferentiated THP‐1 cells were treated with the irreversible PPARγ antagonist, GW 9662, a significant, dose‐dependent decrease in TNFα secretion was observed. These results suggest that the anti‐inflammatory benefit of PPARγ ligands occur independently of classical PPARγ activation.
Characterization of 26 new microsatellite loci in the dugong (Dugong dugon)
Authors: BRODERICK DAMIEN , OVENDEN JENNY , SLADE ROB , LANYON JANET M.
Published: June 2007

Twenty‐six microsatellite loci have been isolated from a dugong (Dugong dugon). The average heterozygosity was 0.52 with two to 10 alleles per locus surveyed from 50 individuals. The markers are suitable for genetic mark–recapture (PID = 5 × 10−16) in dugongs and they could also be used to quantify physical tag loss, estimate relatedness, assign paternity, elucidate population structure and identify migrants. The loci also amplified in Florida manatees (22/26) and Asian elephants (6/26).
Eleven polymorphic microsatellite loci in Lindera benzoin, Lauraceae
Authors: EDWARDS MARTEN J. , NIESENBAUM RICHARD A.
Published: June 2007

Microsatellite markers were developed for studies of the genetic diversity and population substructure of Lindera benzoin, Lauraceae (spicebush). Nuclear microsatellite sequences were obtained from DNA libraries that were enriched for (CA), (GA), (AAG) and (ATG) repeat motifs. From 69 microsatellite sequences, 20 primer sets were developed. Of these, 11 primer pairs resulted in amplified polymorphic loci. In 29 samples of eastern Pennsylvania spicebush plants, the number of microsatellite alleles ranged from two to 16 per locus with observed heterozygosity values ranging from 0.10 to 0.82.
Isolation and characterization of polymorphic microsatellite DNA markers in the Omono type of ninespine stickleback, genus Pungitius
Authors: KOIZUMI NORIYUKI , JINGUJI HIROSHI , TAKAHASHI HIDEAKI , HIGUCHI MASAHITO , TAKATA KEISUKE , MINEZAWA MITSURU , TAKEMURA TAKESHI , MORI ATSUSHI
Published: June 2007

We isolated and characterized 25 polymorphic microsatellite loci for the Omono type of ninespine stickleback, genus Pungitius, an endangered species in streams including agricultural canals in Japan. The number of observed alleles per locus ranged from two to 15 within 32 individuals each collected from three populations in the Omono River, and the values of observed and expected heterozygosities ranged from 0.031 to 0.906 and from 0.031 to 0.856, respectively. All loci conformed to the Hardy–Weinberg equilibrium. Genetic linkage disequilibrium analysis between all pairs of the loci showed no significant departure from the null hypothesis between any of the loci.
Barriers and Facilitators to Children's and Young People's Views Affecting CAMHS Planning and Delivery
Authors: Worrall‐Davies Anne
Published: June 2007

The views of children and young people about the mental health services they receive are central to the tenets of recent government health services policymaking. But do changes to service delivery result from research or projects eliciting children's and young people's views? This article presents evidence that changes may well not result and then discusses what prevents or facilitates CAMHS acting on recommendations gained from user views.
Developing Pilot Befriending Schemes for People with Autism Spectrum Disorders in a Region of Greece: Lessons from Practice
Authors: Mavropoulou Sophia
Published: June 2007

Befriending represents an expanding resource for the social support of vulnerable people in the community. This article discusses the development of two pilot befriending schemes for individuals with Autism Spectrum Disorders (ASDs) in the central region of Greece. In the first part, the context, the aims and participants of the schemes are described and in the next part, the positive aspects and obstacles encountered in both schemes are discussed.
Social Democrats and trade unions in Scandinavia: The decline and persistence of institutional relationships
Authors: ALLERN ELIN HAUGSGJERD , AYLOTT NICHOLAS , CHRISTIANSEN FLEMMING JUUL
Published: June 2007

Abstract.  This article examines the institutional arrangements between Social Democratic parties and trade unions in Denmark, Norway and Sweden. First, the authors show how these relations have weakened at a varying pace. Party–union ties are now quite distant in Denmark, but remain relatively close in Norway and, especially, Sweden. Second, the authors explore this variation using a simple model of political exchange. The finding is that the intensity of the relationship is correlated with the resources that each side can derive from the other, which in turn reflects national differences. Yet it is also clear that the degree of change is related to the formative phase of the institutional arrangement itself: the weaker the ties were from the beginning, the more easily they unravel in response to environmental changes.
Theories of coalition formation: An empirical test using data from Danish local government
Authors: SKJÆVELAND ASBJØRN , SERRITZLEW SØREN , BLOM‐HANSEN JENS
Published: June 2007

Abstract. Theories of coalition formation represent a diverse set of arguments about why some government coalitions form while others do not. In this article, the authors present a systematic empirical test of the relative importance of the various arguments. The test is designed to avoid a circularity problem present in many coalition studies – namely that the theories are tested on data of national government coalitions in postwar Europe: the very data that gave rise to the theories in the first place. Instead, the authors focus on government coalitions at the municipal level. They base their analysis on an expert survey of almost 3,000 local councillors from all municipalities in Denmark. They use conditional logit analysis to model government formation as a discrete choice between all potential governments. The analysis confirms some, but far from all, traditional explanations such as those based on office and policy motives. At the same time, the analysis raises the question of whether actors really seek minimal coalitions.
Herbs and Dietary Supplements in the Prevention and Treatment of Cardiovascular Disease
Authors: Fugh‐Berman Adriane
Published: June 2007

Herbs and dietary supplements can have significant physiological effects. Garlic (Allium sativum) has shown beneficial lipid effects in a majority of trials; dried garlic preparations are superior to oil preparations. There is preliminary evidence that indicates that hawthorn (Crataegus species) may provide benefit in congestive heart failure. Coenzyme Q also may be of benefit in congestive heart failure. Although observational studies indicate a protective effect of dietary or supplemental vitamin E, controlled trials have not shown a beneficial effect on angina and have been mixed on whether supplementation decreases major cardiac events. Although several observational studies have noted that fish intake protects against cardiovascular disease, prospective studies are less impressive. Fish oil supplementation may have a mild beneficial effect on hypertension, but there is no effect on total cholesterol levels. Trials are inconsistent on whether fish oil reduces restenosis rates following coronary angioplasty. Carnitine appears to have beneficial effects on congestive heart failure and angina; there is also preliminary evidence that arginine may benefit patients with congestive heart failure or angina. Herbs and supplements have been associated with adverse effects and interactions; for example, garlic inhibits platelet aggregation and can cause significant anticoagulation, and the Chinese herb danshen (Salvia miltiorrhiza) appears to potentiate warfarin. Several herbs and supplements hold promise as adjuncts in the prevention and treatment of cardiovascular disease. There is a need for definitive research on the potential risks and benefits of these compounds, including appropriate dosages and formulations, and delineation of adverse events and interactions
Lipid Lowering Strategies in Women
Authors: Goldberg Nieca
Published: June 2007

Hyperlipidemia is one of the major modifiable risk factors for coronary heart disease in men and women. There is substantial epidemiological data showing the relationship between elevations in total and low density lipoprotein cholesterol, triglycerides and low high density lipoprotein cholesterol, and coronary heart disease in women. Yet hyperlipidemia is undertreated in women. This may be due to limited data to support intervention for the primary prevention of coronary heart disease, confusion in national guidelines, and inadequate counseling on diet and exercise in clinical practice. Lipid levels should be evaluated in women with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and diabetes. These women should be targeted for aggressive lipid lowering with diet, exercise, and medication. Women with multiple risk factors and early family history of coronary heart disease should also be evaluated. Asymptomatic young women with elevated or borderline lipids should be counseled with regard to lifestyle and behavioral interventions such as diet and exercise.
Behavioral Medicine Strategies for Heart Disease Prevention: The Example of Smoking Cessation
Authors: Guise Barrie J
Published: June 2007

Health related behavior change is one of the most important challenges in the prevention of cardiovascular disease. Lifestyle patterns, such as high fat diet, lack of exercise, persistent smoking, and poor compliance with prescribed medications present the core of this challenge. Conventional wisdom and considerable scientific evidence establish that the barriers to health related behavior change are many and varied. However, much is also known about methods of improving behavioral outcomes. Behavioral medicine strategies incorporate fundamental principles of behavior change together with biomedical and interpersonal approaches to facilitate successful cardiac risk factor modification. Physicians have the most potent opportunity to assist patients with health behavior change. Unfortunately, physicians are least familiar with behavior change technology and the contemporary physician‐patient relationship lacks the partnership needed to succeed in these difficult areas. The good news is that medical education has begun to incorporate training in behavior change and interpersonal effectiveness. A description of the behavioral medicine approach to smoking cessation provides an excellent model for a thoughtful and practical approach to heart disease prevention in every day practice.
Association Between Plasma Homocysteine and Vascular Atherosclerotic Disease in Older Persons
Authors: Aronow Wilbert S.
Published: June 2007

Plasma homocysteine is a risk factor for coronary artery disease, stroke, extracranial carotid arterial disease, peripheral arterial disease, and aortic atherosclerosis in older persons. Randomized trials are in progress investigating whether multivitamin therapy to decrease plasma homocysteine levels will reduce the risk for cardiovascular disease.
Current Concepts in Optimum Nutrition for Cardiovascular Disease
Authors: Platt Riska
Published: June 2007

For the past decade, nutritionists have focused on consensus guidelines (National Cholesterol Education Program) to reduce dietary saturated fatty acids, cholesterol, and excess body weight. However, researchers are looking at other ways that diet may influence the progression of cardiovascular disease, including lipoprotein oxidation, thrombosis progression, cardiac arrhythmia, and medication interaction. Some areas of investigation include the role of various fatty acids and supplements—in the form of vitamins, minerals, herbs, and functional foods—as well as traditional foods and diets from other parts of the world. This review outlines some of the new and relevant nutritional approaches including: specific fatty acids (omega 3, monounsaturated and trans fatty acids), dietary supplements (herbs, antioxidants, vitamins C and E, Coenzyme Q10, B vitamins and homocysteine, L‐arginine, Chinese red yeast rice, garlic, soy, flax seed, and dietary fiber), food and drink (tea, nuts, plant‐sterol and stanolester‐containing spreads, alcohol, and grapefruit juice), and the Mediterranean diet.
Accuracy of Low Load Exercise‐Induced T Wave Normalization in Predicting the Presence of Contractile Reserve After an Anterior Myocardial Infarction
Authors: Mobilia Gianni , Donato Antonino , Satullo Gaetano , Cavallaro Lucio , Buchberger Riccardo , Grassi Rasario
Published: June 2007

Background and Methods. Exercise‐induced T wave normalization occurring at a low (≤ 50 watt) workload in infarct‐related electrocardiographic leads was studied in 30 consecutive patients with a recent transmural anterior acute myocardial infarction. Patients underwent both ergometric stress testing (within 30 days after the infarction) and low dose dobutamine echocardiography. The T wave normalization was considered significant when it occurred in at least two infarct‐related leads. A significant contractile reserve was considered present in an infarcted region when 50% or more of the dyskinetic segments functionally improved on exercise during dobutamine infusion. Results. Eighteen patients showed exercise‐induced T wave normalization (group 1), and 12 patients did not (group 2). Myocardial contractile reserve in the infarct area was detected in 16 patients of group 1 (88%) and in 3 patients (25%) of group 2 (p=0.004). The overall sensitivity, specificity, and diagnostic accuracy of T wave normalization, as it reflects contractile reserve in the infarct area, were 84%, 82%, and 83%, respectively. Conclusion. Low load exercise‐induced T wave normalization in infarct‐related leads appears to be an accurate marker of residual contractile reserve in the infarct area in patients with recent transmural acute anterior myocardial infarction.
Maintaining the Endothelium: Preventive Strategies for Vessel Integrity
Authors: Lissin Lynette Wroblewski , Cooke John P.
Published: June 2007

The endothelium is a diaphanous membrane, only one cell layer thick, that lines all of our blood vessels. Despite its apparent fragility, it exerts profound control over vascular tone, structure, and interaction with circulating blood elements. One of the factors that the endothelium synthesizes is nitric oxide, which is the most potent endogenous vasodilator known. In addition to its blood flow regulating effects, nitric oxide also inhibits key processes in atherosclerosis, including monocyte adherence, platelet aggregation, and proliferation of vascular smooth muscle cells. Nitric oxide synthesis is impaired, and its degradation is accelerated, in many of the conditions associated with atherosclerosis, including hypercholesterolemia. Restoration of nitric oxide synthesis and activity in these disorders can improve blood flow, relieve symptoms, and perhaps reduce the progression of atherosclerosis.
Analysis of Lipoproteins and Body Mass Index in Professional Football Players
Authors: Garry Joseph P. , McShane John J.
Published: June 2007

Exercise is known to improve lipoprotein levels, whereas an elevated body mass index (BMI) is associated with less favorable lipoprotein levels. To date, there have been no reports of lipid analyses in elite athletes who also have BMIs in ranges considered unhealthful. The purpose of this study was to evaluate the lipid‐lipoprotein profiles in a group of professional football players and to determine what association exists between these profiles and the players' BMIs. An observational study was conducted of 70 professional football players from one National Football League team. Measurements included BMI (kg·m−2), and fasting serum lipid analysis. BMI and position played were found to correlate (p<0.001), with linemen having the highest mean BMI, 38.1 kg·m−2. Comparing mean lipid values among BMI categories demonstrated lower high‐density lipoprotein cholesterol levels (p<0.01), higher triglycerides (p<0.05), and higher total cholesterol/high‐density lipoprotein cholesterol ratios (p<0.001) with an increasing BMI. Among the professional football players studied, a lower BMI was associated with a more favorable lipid‐lipoprotein profile. Among the elite athletes in this study with the highest BMIs, exercise may not confer the same protective benefits on cardiovascular risk as it does in those athletes with normal BMIs.
Response of Blood Lipids to Physical Exercise in Elderly Subjects
Authors: Kostka Tomasz , Lacour Jean‐René , Bonnefoy Marc
Published: June 2007

Regular physical activity plays an important role in nonpharmacologic management of hyperlipidemia, in both the primary and secondary prevention of coronary heart disease. Training intensity and duration, health status (especially the presence of cardiovascular disease), and concomitant changes in body mass and dietary habits are the most important factors that can modify the physical activity‐blood lipid profile relationship in the elderly. The benefit of regular exercise goes beyond direct influence on blood lipids; it aids in reducing weight, decreasing fat mass, increasing lean body mass, reducing elevated blood pressure, and increasing insulin sensitivity. Regular physical activity has become widely recommended as an important element of healthy and successful aging and should be encouraged in individuals without contraindications.
Effect of Controlling Hypercholesterolemia on Myocardial Ischemia
Authors: Favarato Desiderio , De Padua Mansur Antonio
Published: June 2007

Hypercholesterolemia causes myocardial ischemia, even in the absence of obstructive coronary artery lesions. Reductions in cholesterol are associated with improved clinical outcomes that may reflect reversal of endothelial dysfunction, lesion regression, or both. This review explores experimental and clinical evidence that supports these observations. These include: 1) mechanisms by which hypercholesterolemia (and other risk factors for coronary artery disease) causes endothelial dysfunction; 2) the role that hypercholesterolemia and endothelial dysfunction play in atherogenesis, lesion complications, and clinical ischemic syndromes; and 3) compelling data that illustrate the benefits of cholesterol control. The latter include transformation of the plaque lipid composition to a more favorable profile, improved blood pressure control, normalization of exercise test results, improved exercise tolerance, and reversal or prevention of myocardial perfusion abnormalities. Collectively, these data support the notion that control of cholesterol is important to both the prevention and treatment of cardiac disease.
Emergence of Obesity and Cardiovascular Risk for Coronary Artery Disease: The Bogalusa Heart Study
Authors: Berenson Gerald S. , Srinivasan Sathanur R.
Published: June 2007

The underlying determinants of cardiovascular risk are governed by both genetic and lifestyle factors. One of the major adverse outcomes of unhealthy lifestyles is obesity, the genesis of which begins in childhood. Obesity, an important risk factor for atherosclerotic cardiovascular disease, type 2 diabetes, and hypertension, persists (tracks) strongly from adolescent years to adulthood. Secular trends toward increased obesity in the past 25 years have occurred in children and adults alike. Of interest, baseline adiposity precedes hyperinsulinemia in all age groups, independently of race, sex, and baseline insulin levels. Adiposity is an independent predictor of the risk of developing the cluster of risk variables of the metabolic syndrome X, beginning in childhood. Exposure to a multiple risk factor burden over time enhances the development of coronary atherosclerosis and hypertensive cardiovascular disease. In fact, autopsy studies in youths have shown that the extent of fibrotic atherosclerotic plaques in coronary arteries, measured antemortem, increases markedly with the presence of syndrome X risk variables. Further, in overweight children, insulin levels are associated with left ventricular mass. In young people, overnutrition, coupled with physical inactivity, leads to weight gain. Since obesity, unhealthy dietary habits, and a sedentary lifestyle are interrelated and modifiable, prevention and intervention must begin in early life.
Distribution of C‐Reactive Protein and Its Relation to Risk Factors and Coronary Heart Disease Risk Estimation in the National Health and Nutrition Examination Survey (NHANES) III
Authors: Wong Nathan D. , Pio Jose , Valencia Rosemary , Thakal Gaurav
Published: June 2007

The authors examined the distribution of, and risk factors associated with, the inflammatory marker C‐reactive protein (CRP) among a large sample of non‐institutionalized American adults aged 30–74 years of age, and its relation to estimated 10‐year coronary heart disease risk. The population studied comprised 4472 men and 5212 women aged 30–74 years, without coronary heart disease, who had CRP measurements in the Third National Health and Nutrition Examination Survey (NHANES III). The 10‐year risk of coronary heart disease was estimated from Framingham risk factor algorithms among those with CRP levels of ≤ 0.21 mg/dL, >0.21–<0.5mg/dL, 0.5–<1.0 mg/dL, and ≥1.0 mg/dL. Mean (SD) levels of CRP were 0.41 (0.64) mg/dL in men and 0.55 (0.91) mg/dL in women. Levels of at least 1 mg/dL were measured in 6.4% of men and 12.9% of women. CRP levels were highest among non‐Hispanic black men and Mexican‐American women. According to multiple logistic regression analysis, cigarette smoking and increased age, body mass index, and systolic blood pressure in men, and body mass index and diabetes in women, were strongly associated with a greater likelihood of CRP levels of ≥1.0 mg/dL (p<0.001). Among persons with CRP levels of ≥0.21 mg/dL, >0.21‐<0.5 mg/dL, 0.5‐<1.0 mg/dL and ≥1.0 mg/dL, the 10‐year estimated risk of coronary heart disease were 13.4%, 17.6%, 19.6%, and 21.1% among men, respectively, and 2.7%, 3.6%, 4.1% and 4.3% among women, respectively (both p<0.001 across CRP categories); higher risks across CRP groups were also found among ethnic/gender subgroups. CRP remained a significant predictor of coronary heart disease risk in unadjusted and age‐adjusted analyses. Conclusion. Elevation of CRP is associated with several major coronary heart disease risk factors and with unadjusted and age‐adjusted projections of 10‐year coronary heart disease risk in both men and women.
Original Metric vs. Standardized Effect Sizes for Meta‐Analysis of Clinical Data
Authors: Kelley George A. , Tran Zung Vu
Published: June 2007

This study compared the use of the original metric effect size with the standardized effect size for clinical data in meta‐analysis. The example data set included 17 controlled clinical trials dealing with the effects of progressive resistance exercise on resting diastolic blood pressure in adults. Original metric effect size showed a decrease in resting diastolic blood pressure of −2.07 mm Hg (95% confidence interval, −3.60 to −0.54). From a clinical standpoint, this is considered a “small” effect. The standardized approach showed an average effect of −0.21, 95% CI= −0.39 to −0.02. This is also considered a “small” effect. When possible, use of the original metric is preferred because it can be more clinically meaningful and will enhance interpretation of blood pressure results for a wider range of readers.
Cardiovascular Disease Risk Stratification and Comparison in a California Population
Authors: Lin Zihui , Meng Ying‐Ying , Leung Kwan‐Moon , Jatulis Darius E. , Welsh Nancy J. , Zaher Carol A. , Legorreta Antonio P.
Published: June 2007

This study was designed to identify the need for primary prevention of cardiovascular disease in an HMO population and to develop appropriate interventions for individuals in different risk groups, based on risk stratification and comparison. The analysis is based on a cross‐sectional survey of the HMO members of a large employer group. Respondents (n=17,878) were stratified based on the Framingham model; 34% of respondents without cardiovascular disease were classified as moderate to high attributable risk for the disease, and 66% were classified as low attributable risk. Results of logistic regression analyses suggest that, compared with respondents with pre‐existing cardiovascular disease, moderate‐ to high‐risk respondents are more likely to smoke, have unhealthy diets, and be overweight, hypertensive, and hypercholesterolemic. More low‐risk respondents had unhealthy diets than did those with preexisting cardiovascular disease. There were no differences between these groups for physical activity and stress. Respondents had fewer modifiable risk factors and healthier lifestyles than did those who were at risk. These findings suggest that primary prevention should be enhanced, especially among those with significantly increased risk for the disease. Moreover, the approaches of this project—population‐based risk assessment, stratification, and comparison—were instrumental in identifying the target population and designing appropriate interventions.
Genetics and Blood Pressure Response to Exercise, and Its Interactions With Adiposity
Authors: Rankinen Tuomo , Bouchard Claude
Published: June 2007

Regular aerobic exercise has the potential to induce several beneficial health effects, including a decrease in blood pressure level, especially in hypertensive patients and in subjects with high‐normal blood pressure. However, it is also well documented that some people show more pronounced blood pressure responses to endurance training than others, despite identical training programs and similar initial blood pressure levels. This kind of variation is an example of normal biologic diversity and most likely originates from interactions with genetic factors. Data from genetic epidemiologic studies indicate that there is a genetic component that affects both resting blood pressure and blood pressure responses to acute exercise. Evidence from molecular genetic studies is scarce, but the first reports suggest that DNA sequence variation in the hypertension candidate genes, such as angiotensinogen, also modify blood pressure responses to endurance training. The current knowledge regarding the role of genetic factors in the modification of blood pressure responses to endurance training will be summarized and discussed.
Peripheral Arterial Disease: Medical Care and Prevention of Complications
Authors: Dawson David L. , Hiatt William R. , Creager Mark A. , Hirsch Alan T.
Published: June 2007

Peripheral arterial disease (PAD) is a common but under‐recognized problem affecting older patients. Intermittent claudication is the most frequent symptom of PAD, although the diagnosis of PAD is often overlooked until the patient presents with limb‐threatening ischemia. Importantly, PAD is a marker for generalized atherosclerosis and is closely associated with coronary and cerebrovascular disease. The severity of PAD has been correlated with an increased risk of myocardial infarction, stroke, and cardiovascular death. The recognition and diagnosis of PAD, combined with its appropriate medical management, may well reduce the overall risk of cardiovascular morbidity. When diagnosed early, both exercise and pharmacotherapy can ameliorate symptoms of claudication, augment functional performance, and improve quality of life.
Intraindividual Variability of Children's Blood Lipid and Lipoprotein Concentrations: A Review
Authors: Tolfrey Keith
Published: June 2007

Of the numerous risk factors that have been associated with atherosclerosis and subsequent coronary heart disease, none have caught the public's attention more than plasma cholesterol. An increasing number of studies are focusing on intervention strategies aimed at “improving” the plasma lipid‐lipoprotein profile of children. However, the efficacy of these strategies cannot be ascertained unless the biologic and analytic variability of these metabolites has been determined. From the limited available literature, it would appear that the biologic variability of total cholesterol, high‐and low‐density lipoprotein cholesterol, and triacylglycerol in children is similar to that reported for adults. Yet studies that have directly focused on this important issue with children are scarce, especially those that have included a representative sample and measurements of lipoprotein subfractions. Further research is warranted with children to better establish the extent of intraindividual variation associated with the lipid‐lipoprotein profile.
The Significance of Measuring Non‐HDL‐Cholesterol
Authors: Hirsch Glenn A. , Vaid Nidhi , Blumenthal Roger S.
Published: June 2007

The third Adult Treatment Panel of the National Cholesterol Education Program has recently issued revised guidelines for the treatment of cholesterol in adults. Increased attention to the metabolic syndrome and diabetes, including the inaccuracy of the low‐density lipoprotein cholesterol (LDL‐C) measurement in these patients because of elevated triglycerides is highlighted. To overcome the inaccuracy of the Friedewald equation in calculating LDL‐C when the triglycerides are elevated, measuring non‐high‐density lipoprotein (non‐HDL‐C) may provide a better means to follow these patients toward their treatment goals. Recently, non‐HDL‐C was shown to be a better predictor of cardiovascular death than LDL‐C, even in patients with triglyceride levels below 200 mg/dL. The authors review the basis for using non‐HDL‐C as a treatment target for cholesterol, in comparison with other lipoproteins.
A Review of Electron Beam Computed Tomography: Implications for Coronary Artery Disease Screening
Authors: Redberg Rita F. , Shaw Leslee J.
Published: June 2007

Coronary artery disease is the leading cause of death in the United States, thus the intense interest in a screening test that would allow early identification of coronary artery disease in its asymptomatic stage, allowing early aggressive targeted risk factor reduction. While office‐based risk factor assessment is currently the reference standard for prediction of cardiac risk, several imaging tests are currently being investigated. Electron beam computed tomography (EBCT) can accurately identify calcium in the coronary tree noninvasively. Coronary calcium is clearly linked with coronary atherosclerosis. In population studies, populations with higher calcium scores have more calcium events. The predictive value of a calcium score for an individual is currently under investigation, as well as the incremental value of a calcium score over office‐based risk assessment in cardiac risk prediction. This review looks at the current role of EBCT in the prevention of cardiovascular disease. It summarizes the current data for calcium as a screening tool, which is strongest in establishing that asymptomatic people undergo increased rates of revascularization after an EBCT test. Widespread clinical use of EBCT is not recommended, pending data to establish its efficacy in the role of risk factor reduction and prevention of cardiovascular disease
Treatment of Atherosclerosis in the New Millennium: Is There a Role for Vitamin E?
Authors: Meagherx Emma A.
Published: June 2007

Oxidative stress appears to be of fundamental relevance to diseases as diverse as atherosclerosis, cancer, and Alzheimer's disease. Observational data in humans have suggested that antioxidant vitamin intake is associated with reduced cardiovascular disease. Animal studies are largely consistent with the concept that dietary supplementation with antioxidant vitamins reduces the progression of atherosclerosis. However, recent prospective, controlled clinical trials of vitamin E, including the Cardiovascular Disease, Hypertension and Hyperlipidemia, Adult‐Onset Diabetes, Obesity, and Stroke (CHAOS) study, the Heart Outcomes Prevention Evaluation (HOPE) trial, Gruppo Italiano per lo Studio della Sopravvivvenza nell'Infarto Miocardico (GISSI)‐Prevenzione trial, the Secondary Prevention with Antioxidants of Cardiovascular Disease in End Stage Renal Disease (SPACE) trial, and the Heart Protection Study (HPS) present a confused picture. The various possibilities that have been advanced to explain this discrepancy are discussed in this review. A striking feature of these and other trials of antioxidants is the absence of a biochemical basis for patient inclusion or, indeed, dose selection. Patients with high levels of oxidant stress or depletion of natural antioxidant defense systems may be the most likely to benefit from antioxidant therapy. If this is the case, then reliable, quantitative indices of in vivo oxidant stress such as urinary isoprostane levels should be considered as an inclusion criterion for patient selection. Future trials of antioxidant therapy in cardiovascular disease should then be targeted toward such patients with high levels of oxidant stress or patients with depletion of natural antioxidant defense systems. Furthermore, the dose of antioxidant should be chosen based on a surrogate readout that is a reliable, reproducible, and easily obtainable in vivo measure of oxidant stress. In the interim, although the safety of vitamin E up to doses of 800 IU/day has been determined, the conflicting nature of the results published to date encourages us to avoid making premature recommendations with respect to vitamin E supplementation in the prevention and treatment of cardiovascular disease.
A Prospective Study in Primary Care in Patients Without Vascular Disease Comparing Levels of Coronary Risk Factors in Those Recommended for Lipid‐Lowering Drugs Based on Either Absolute Risk or Absolute Risk Reduction
Authors: Ramachandran Sud , Croft Peter , Neary Richard H.
Published: June 2007

In the United Kingdom, the current recommendation is that lipid‐lowering drugs should be prescribed for primary prevention only to subjects with an absolute coronary risk (AR) greater than 15% in 5 years (i.e., myocardial infarction or angina). However, to achieve greater benefit it may be preferable to direct treatment to those patients showing the greatest absolute risk reduction (ARR). The aim of this study was to compare the characteristics of subjects eligible for lipid‐lowering drugs based on the AR criteria or on an ARR of >4.45%. A prospective study was carried out over 29 months in primary care in a part of the United Kingdom with a prevalence of coronary disease nearly 20% above the national average. Risk factors were recorded in men and women aged 30–75 years who were being considered by their primary care physician for lipid‐lowering drug therapy. Of the 2351 patients included in the study, 2139 (91%) and 101 (4.3%) were, respectively, below and above the criteria for treatment by both AR and ARR criteria. In 111 (4.7%) subjects, treatment was recommended based on only one of the criteria—82 on AR and 29 on ARR. Comparing these two groups, those treated on AR only were older (mean age 68.1 years [SD, 4.1] vs. 49.1 years [SD, 4.6]; p<0.0001) and had a lower total cholesterol (260 vs. 288 mg/dL; p=0.015); higher high‐density lipoprotein cholesterol (50 vs. 43 mg/dL; p=0.003), lower low‐density lipoprotein cholesterol (160 vs. 184 mg/dL; p=0.03), a lower total to highdensity lipoprotein cholesterol ratio (5.4 vs. 7.1; p<0.0001), and lower triglycerides (258 vs. 435 mg/dL; p=0.007). The AR group also had a higher mean systolic blood pressure (170.9 vs. 158.9 mm Hg; p=0.013), presumably an attribute of their greater age. Although the AR and ARR groups did not show a difference in the proportion of males or diabetics, there was a significantly greater proportion of smokers in the latter group (72% vs. 35%; p=0.001). In conclusion, treatment recommendations based on AR alone would result in nontreatment of young subjects with significant hyperlipidemia and at high relative risk of coronary disease, whereas lipid‐lowering drugs would be given preferentially to patients whose main coronary heart disease risk factors are age and hypertension but not hyperlipidemia. By contrast, treatment recommendations based on ARR ensure that lipid‐lowering drugs are directed to patients who will derive the most benefit. Furthermore, delaying treatment in younger subjects at high relative risk but not high AR results in their accumulating significant coronary risk in the years before their AR exceeds an arbitrary threshold before lipid‐lowering drugs are prescribed.
Consumption of Fish and Fish Oils and Decreased Risk of Stroke
Authors: Skerrett P.J. , Hennekens Charles H.
Published: June 2007

Consumption of fish and fish oils was first associated with decreased risk of cardiovascular disease almost 50 years ago. Since then, a number of epidemiologic studies have evaluated whether their consumption is specifically associated with stroke. Ecologic/cross‐sectional and case‐control studies have generally shown an inverse association between consumption of fish and fish oils and stroke risk. Results from five prospective studies have been less consistent, with one showing no association, one showing a possible inverse association, and three demonstrating a significant inverse association. In the latest and largest of these, the Nurses' Health Study, the relative risk of total stroke was lower, although not significantly so, among women who regularly ate fish than among those who did not. A significant decrease in the risk of thrombotic stroke (relative risk, 0.49; 95% confidence interval, 0.26–0.93) was observed among women who ate fish at least two times per week compared with women who ate fish less than once per month, after adjustment for age, smoking, and other cardiovascular risk factors; a nonsignificant decrease was observed among women in the highest quintile of long‐chain omega‐3 polyunsaturated fatty acid intake. No association was observed between consumption of fish or fish oil and hemorrhagic stroke. These data support the hypothesis that consumption of fish several times per week reduces the risk of thrombotic stroke but does not increase the risk of hemorrhagic stroke.
Impact of Age on Definition of Standards for Ideal Weight
Authors: Heiat Asefeh
Published: June 2007

There has been an ongoing debate regarding the impact of age while establishing standards for ideal weight. Based on current federal guidelines released by the National Heart, Lung, and Blood Institute, ideal weight is defined as a body mass index between 18.7–24.9 for all adults regardless of age. However, studies failed to show a positive association between overweight—as defined by the current guidelines—and all‐cause and cardiovascular mortality in individuals 65 years and older. Data suggest that optimum body mass index tended to be higher for older adults compared with the young and middle‐aged population, and interestingly, being heavier than recommended by the current guidelines resulted in the lowest mortality rates. Therefore, allocation of time and resources for weight reduction interventions among the mild‐ to moderately‐overweight elderly is not advisable. To establish standards for ideal weight, future guidelines should consider age‐specific recommendations that reflect the results of recent studies.
Obesity and the Risk for Cardiovascular Disease
Authors: Rashid Mitchell N. , Fuentes Francisco , Touchon Robert C. , Wehner Paulette S.
Published: June 2007

Coronary heart disease (CHD) is the leading cause of mortality in the United States. Hypertension, diabetes mellitus, hypercholesterolemia, and smoking have all been directly related to CHD. Obesity is on the rise in the United States and has also been associated with CHD. This review clearly establishes obesity as an independent risk factor for CHD as demonstrated by the Framingham Heart Study, Nurses' Health Study, Buffalo Health Study, and the Cancer Prevention Study II. Morbid obesity was found to correlate with a significant risk of mortality from CHD, especially in young men. Prevention of obesity, and therefore reduction in risk from cardiovascular disease, is paramount in the management of obesity. New approaches to behavioral, medical, and surgical management of obesity are reviewed, including thalidomide, an antiangiogenic agent. A primary and secondary prevention model details a multidisciplinary approach to reducing risk in obesity.
Screening for Diabetes in General Practice
Authors: Lawrence James , Robinson Anthony
Published: June 2007

The prevalence of type 2 diabetes is rising rapidly worldwide. Evidence suggests that between one third and one half of cases are undiagnosed and patients may have preclinical disease for as long as 12 years. At diagnosis, 50% of patients have microvascular complications (retinopathy, neuropathy, or nephropathy) and patients have twice the risk of macrovascular disease compared to the background population. Screening for type 2 diabetes would allow earlier recognition of cases, with the potential to intervene earlier in the disease course, but whether this would result in improved long‐term outcomes is unknown. The debate continues about who should be considered for screening, how we should screen, and whether we should screen for diabetes at all. The authors review the evidence, particularly in light of the recent position statement on diabetes screening published by the American Diabetes Association. If we do start screening for diabetes, one of the major challenges ahead is to ensure resources are in place to allow optimization of treatment for the increasing number of patients. This is important both in those found to have diabetes and in those with lesser degrees of glucose intolerance who are at high risk of developing diabetes and are at increased risk of macrovascular disease.