Role In Cardiovascular Health Research Articles

William E. Connor, MD

Bill Connor, a pioneer in lipid and atherosclerosis research, passed away in Portland, Oregon, on October 25 at the age of 88. This gracious and unassuming man was an innovative biomedical investigator, stimulating teacher, and compassionate physician. His scientific curiosity and courage to challenge existing concepts enabled him to make seminal contributions to lipid metabolism and its role in cardiovascular health and disease. Bill completed undergraduate studies at the University of Iowa in 1942 and served in the United States Army Signal Corps during World War II. After receiving his MD degree from the University in 1950, he began postgraduate training, spent 2 years in private practice, and then completed a medical residency at the Iowa City Veterans Administration Medical Center. He was appointed to the University of Iowa faculty in 1956 as an Instructor in Internal Medicine and rapidly rose to the rank of Professor. Bill was a pioneer in the treatment of hyperlipidemia and achieved national recognition while at Iowa for his studies in lipid nutrition, cholesterol metabolism, and atherosclerosis. In 1975 he moved to the Oregon Health and Science University, where he maintained a vigorous and productive research program in lipids and nutrition until the time of his death. During his tenure at Iowa, Bill was Principal Investigator of a Program Project in Lipids and Thrombosis and the Arteriosclerosis Specialized Center of Research. In addition, he served as Director of the Lipid Research Clinics Program …

The effects of iron deficiency anemia on p wave duration and dispersion

OBJECTIVES:The association between P wave dispersion and iron deficiency anemia has not been documented in the literature. In this study, we evaluated P wave dispersion in patients with iron deficiency anemia and the possible relationships between P wave dispersion and other echocardiographic parameters.INTRODUCTION:The iron status of an individual may play an important role in cardiovascular health. Anemia is an independent risk factor for adverse cardiovascular outcomes. P wave dispersion is a simple electrocardiographic marker that has a predictive value for the development of atrial fibrillation. Apart from cardiovascular diseases, several conditions, such as seasonal variation, alcohol intake and caffeine ingestion, have been demonstrated to affect P wave dispersion.METHODS:The study included 97 patients who had iron deficiency anemia and 50 healthy subjects. The cases were evaluated with a clinical examination and diagnostic tests that included 12‐lead electrocardiography and transthoracic echocardiography.RESULTS:Compared to the control group, patients with iron deficiency anemia showed significantly longer maximum P wave duration (Pmax) (91.1±18.0 vs. 85.8±6.7 msec, p = 0.054), P wave dispersion (PWD) (48.1±7.7 vs. 40.9±5.6 msec, p<0.001), mitral inflow deceleration time (DT) (197.5±27.9 vs. 178.8±8.9 msec, p<0.001) and isovolumetric relaxation time (IVRT) (93.3±9.2 vs. 77.4±8.2 msec, p<0.001); they also showed increased heart rate (85.7±16.1 vs. 69.0±4.4, p<0.001) and frequency of diastolic dysfunction (7 (7.2%) vs. 0). Correlation analysis revealed that PWD was significantly correlated with IVRT, DT, heart rate, the presence of anemia and hemoglobin level.CONCLUSIONS:Iron deficiency anemia may be associated with prolonged P wave duration and dispersion and impaired diastolic left ventricular filling.

What are omega-3 fatty acids and what is their role in cardiovascular health?

What are omega-3 fatty acids and what is their role in cardiovascular health?

Review of Exercise and the Risk of Benign Prostatic Hyperplasia

It has been long appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Since 1995, 14 studies have been identified that investigate the clinical relationship between exercise and BPH/LUTS. No randomized controlled trials have been performed, but useful prospective cohort data originating from recent publications on the medical treatment of BPH and prevention of prostate cancer are available. Most of the literature supports a clinically significant, independent, and strong inverse relationship between exercise and the development of BPH/LUTS. Several mechanisms for this relationship have been proposed, including decreased sympathetic tone, avoidance of metabolic syndrome, and reduced oxidative damage to the prostate.

Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia

It has long been appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH). Prospective cohort data originating from recently published randomized trials on the medical treatment of BPH and prevention of prostate cancer have been invaluable. A growing body of evidence suggests that exercise and the intake of specific macronutrients and micronutrients through regular diet play a beneficial role. Most strikingly, the magnitude of these effects is similar to medical therapies using alpha-blockers and 5-alpha-reductase inhibitors. The use of supplements for prostate disease is a multibillion dollar business in the United States, and supplements are more commonly prescribed than medical therapy in many countries. In contrast to consumption of micronutrients through regular diet, supplemental intake of micronutrients and phytotherapies currently lack evidence to support their efficacy.

Impact of Omega-3 and Trans Fatty Acids on Vascular Remodeling:Opposing Roles in Cardiovascular Health

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have well-recognized cardio-beneficial effects that include reductions in atherosclerotic lesions and mortality from myocardial infarction, stroke, and sudden cardiac death. In contrast, evidence suggests that more than 30,000 premature coronary deaths per year in the US alone are associated with consumption of high levels of trans isomers of unsaturated fatty acids, or trans fatty acids (TFAs). Epidemiological evidence from four large cohort studies overwhelmingly supports the conclusion that TFAs are linked to coronary heart disease (CHD). CHD in patients is associated with pathological vascular remodeling (PVR) and impaired compensatory vascular remodeling (CVR). PVR is characterized by thickening of vessel walls, reduction in elasticity, and occlusion of vessels, resulting in restricted blood flow. CVR represents a physiological process whereby vessels from a pre-existing arteriolar network develop into collateral arteries, effectively bypassing the site of arterial occlusion. The structure and function of vascular endothelial cell membranes are altered by both PVR and CVR. Oxidative stress and the induction of endothelial adhesion molecules promote PVR and inhibit CVR. It is known that n-3 PUFAs inhibit the release of soluble adhesion molecules and proinflammatory cytokines whereas TFA consumption has been linked to an increased release of these proinflammatory mediators. However, it is not known whether the changes in cell membrane composition induced by n-3 PUFAs or TFAs impact development of PVR and CVR directly or whether the changes result indirectly from altered expression and/or release of proinflammatory mediators. This review summarizes studies suggesting that n-3 PUFAs and TFAs have opposing effects on endothelial cells and that their effects on the endothelium might play an important role in vascular remodeling.

Transient receptor potential vanilloid channels in hypertension, inflammation, and end organ damage: an imminent target of therapy for cardiovascular disease?

The possible role of several neurohormonal factors in pathogenesis of hypertension has been studied extensively both in humans and in experimental animal models. However, controversial data from some previous studies are indecisive and call for reassessment and development of new targets. This mini-review presents some of the most recent findings about the role of transient receptor potential vanilloid type 1 channels in the development of hypertension and its pathology. The transient receptor potential vanilloid type 1, channel activated by novel endovanilloids or altered pH, temperature, and/or local hemodynamics, may serve as a distinct molecular sensor detecting sodium and water balance and may play a role in preventing salt-induced hypertension and tissue damage. Impairment of the function of the transient receptor potential vanilloid type 1 channels may contribute to increased salt sensitivity, inflammation, and end organ damage. Emerging evidence indicates that the transient receptor potential vanilloid type 1 channel plays a key role in cardiovascular health and disease by acting as a sensor and regulator of cardiovascular homeostasis and a protector against cardiovascular injury. Given the huge population who suffers from cardiovascular disease, the study of the transient receptor potential vanilloid channels may improve our understanding of pathogenesis of several common cardiovascular disorders and may lead to the development of therapy for hypertension, inflammation, and organ damage.

The role of urotensin II in cardiovascular and renal physiology and diseases

Urotensin II (U-II) is a cyclic neuropeptide that was first isolated from teleost fish some 35 years ago. Mammalian U-II is a powerful vasoconstrictor with a potency greater than that of endothelin-1.Nevertheless, unlike endothelin-1, which constricts all or nearly all vascular beds, the vasoactive effects of U-II are reported to be dependent both on the species and on the regional vascular bed examined. Typical regional variability occurs in the rat in which vasoconstriction to U-II is most robust in thoracic aorta proximal to the aortic arch and decreases gradually towards the distal peripheral arteries. As small peripheral arteries but not larger arteries such as the aorta play a major role in regulating peripheral resistance and consequent blood pressure as well as workload on the heart, doubts have been raised concerning the importance of this peptide in cardiovascular physiology. Moreover, an interaction between U-II and other endogenous vasoactive molecules may add a level of complexity to the vascular actions of U-II.On the other hand, recent experimental and clinical studies have revealed increased expression of U-II and urotensin receptor (UT receptor) in animals with experimentally induced myocardial infarction, heart failure, and in patients with hypertension, atherosclerosis, and diabetic nephropathy, which suggests a potential role for U-II in both cardiovascular and renal diseases. A series of peptidic and nonpeptidic UT receptor ligands have been shown to be effective in antagonizing the effects of U-II in the cardiorenal system. This article aims to review recent advances in our understanding of the physiology and pathophysiology of U-II with particular references to its role in cardiovascular health and disease.

Cellular mechanisms underlying the cardiovascular actions of oestrogens

Although pre-menopausal women enjoy relative cardiovascular protection, hormone (oestrogen+/-progestin)-replacement therapy has not shown cardiovascular benefits in post-menopausal women, suggesting that the effects of oestrogens on the cardiovascular system are much more complex than previously expected. Endothelial cells, smooth muscle cells, cardiac myocytes and fibroblasts, the cellular components of blood vessels and the heart, play important roles in cardiovascular health and disease. During the development and progression of cardiovascular disease, changes occur both in the structure and function of these cells, resulting in a wide range of abnormalities, which affect growth, death and physiological function. These cells contain functional oestrogen receptors and are targets for oestrogen action. This review focuses on recent studies on the effects of oestrogen on cardiovascular cell function. Oestrogens, particularly 17beta-oestradiol, exert multiple effects on cardiovascular cells, and these effects may contribute to the gender-associated protection against cardiovascular diseases.

Renal osteodystrophy in children: A systemic disease associated with cardiovascular manifestations

The increasing prevalence of chronic kidney disease (CKD) in the United States demands a closer evaluation of and attention to associated morbidities, and, particularly, the rising mortality related to cardiovascular disease in all age groups. Patients with CKD demonstrate an increased risk of coronary artery disease due to calcium deposition and subsequent arterial stiffening, in addition to left ventricular dysfunction with associated heart failure and arrhythmias. While clearly impacted by the traditional risk factors for development of cardiovascular disease (CVD), patients with CKD are also affected by non-traditional risk factors, including calcium overloading related to aggressive management of secondary hyperparathyroidism. Recent data have shown that a substantial number of patients with CKD are deficient in vitamin D on a nutritional basis, in addition to the known decrease in the kidney-produced active metabolite during progressive CKD. Historically, vitamin D has been described as an endocrine hormone that regulates blood calcium and parathyroid hormone levels. It has become increasingly clear, through the recognition of a vitamin D receptor in most tissues, that vitamin D possesses functions well beyond calcium homeostasis, such that a deficiency may contribute to the development of CVD. In this brief review, the role of vitamin D activation through its vitamin D receptor will serve as an introduction to the magnitude of the nutritional deficits in children, adults, and those with CKD. As therapeutic entities in the management of renal osteodystrophy, vitamin D analogues play an important role in cardiovascular health that continues to evolve. Preliminary studies indicate that vitamin D therapy for control of secondary hyperparathyroidism may confer cardioprotection and reduce mortality. Attention to care of osteodystrophy in CKD must take into account heart health as well.

Omega-3 Fatty Acids

Dietary omega-3 polyunsaturated fatty acids, eicosapentaenoic and docosahexaenoic acids, play an important role in cardiovascular health and disease. Clinical trials provide substantial evidence to support current dietary recommendations for omega-3 fatty acids in cardiovascular disease management. The cardioprotective benefits of omega-3 fatty acids may be attributed to multiple physiological effects on lipids, blood pressure, vascular function, cardiac rhythms, platelet function, and inflammatory responses. The metabolism of omega-3 fatty acids, physiological effects, and clinical considerations with current dietary recommendations and sources of omega-3 fatty acids are presented.

The nutraceutical Pycnogenol: its role in cardiovascular health and blood glucose control

Pycnogenol® (a registered trademark of Horphag Research Ltd.) is French maritime pine bark extract of the outer bark of Pinus pinaster Ait. Subsp. atlantica. Its specificationsaredescr ibedinthe USP 28-Dietary supplements. Pycnogenol has strong antioxidant profile proven by in vitro and in vivo studies and further confirmed in clinica ltrials. Its strong antioxidant profile, vasodilator activity, antithrombotic effect and collagen stabilizing property make it a unique health product. In humans, Pycnogenol has been shown to lower blood pressure in mild to moderate hypertensive individuals and blood glucose levels in diabetics. In this review the diverse biological effects of Pycnogenol are presented and discussed using a target-oriented approach, in health and disease conditions like edema, inflammation, chronic venous insufficiency, deep vein thrombosis, diabetes, diabetic retinopathy, and hypertension. The future trends are the continuous efforts proving its efficacy inconditions which involves oxidative stress and inflammation. Recent preliminary study utilizing high throughput methodology and nutrigenomics approach are able to provide a new insight into the molecular mechanism of the biological activity of this botanical sourced nutraceutical. Biomedical Reviews 2005; 16: 49-57.

Estrogen-related genes and blood pressure: an example of the complexity of advanced association studies

Estrogen-related genes and blood pressure: an example of the complexity of advanced association studies

Endothelin and endothelin antagonism: Roles in cardiovascular health and disease

Endothelin is the most potent mammalian vasoconstrictor yet discovered. Its three isoforms play leading roles in regulating vascular tone and causing mitogenesis. The isoforms bind to two major receptor subtypes (ETA and ETB), which mediate a wide variety of physiologic actions in several organ systems. Endothelin may also be a disease marker or an etiologic factor in ischemic heart disease, atherosclerosis, congestive heart failure, renal failure, myocardial and vascular wall hypertrophy, systemic hypertension, pulmonary hypertension, and subarachnoid hemorrhage. Specific and nonspecific receptor antagonists and ECE inhibitors that have been developed interfere with endothelin's function. Many available cardiovascular therapeutic agents, such as angiotensin-converting—enzyme inhibitors, calcium-entry blocking drugs, and nitroglycerin, also may interfere with endothelin release or may modify its activity. The endothelin antagonists have great potential as agents for use in the treatment of a wide spectrum of disease entities and as biologic probes for understanding the actions of endothelin in human beings.

The questionable wisdom of a low-fat diet and cholesterol reduction

The prevalent wisdom that a low-fat diet and cholesterol reduction are essential to good cardiovascular health is coming under increased scrutiny. An examination of the foundations of this view suggests that in many respects it was ill-conceived from the outset and, with the accumulation of new evidence, it is becoming progressively less tenable. Cross-sectional, longitudinal and cross-cultural investigations have variously suggested that the relationship between dietary fat intake and death from heart disease is positive, negative and random. These data are incompatible with the view that dietary fat intake has any causal role in cardiovascular health. Although hypercholesterolemia is associated with increased liability to death from heart disease, it is as frequently associated with increased overall life expectancy as with decreased life expectancy. These findings are incompatible with labelling hypercholesterolemia an overall health hazard. Moreover, it is questionable if the cardiovascular liability associated with hypercholesterolemia is either causal or reversible. The complex relationships between diet, serum cholesterol, atherosclerosis and mortality and their interactions with genetic and environmental factors suggest that the effects of simple dietary prescriptions are unlikely to be predictable, let alone beneficial. These cautions are borne out by numerous studies which have shown that multifactorial primary intervention to lower cholesterol levels is as likely to increase death from cardiovascular causes as to decrease it. Importantly, the only significant overall effect of cholesterol-lowering intervention that has ever been shown is increased mortality. The stress and helplessness associated with misapprehensions as to the dangers of dietary fat and the asceticism inherent in the war on cholesterol have considerable implications for health practices. Recent research in behavioral immunology suggests that stress and helplessness are likely to compromise immunity and promote ill-health.