A computerized test battery for the assessment of cardiovascular reactivity

Recent evidence has suggested a possible relationship between the tendency to exhibit excessive cardiovascular reactions during psychological challenge and the risk of cardiovascular disease. Valid techniques for reliably assessing such reactions are, however, minimally available. A test battery for the assessment of cardiovascular reactivity to experimental challenge is currently being developed at the University of Pittsburgh in conjunction with the University of Miami and Duke University. An IBM-AT compatible microcomputer is being used for the concurrent collection of physiological data and presentation of the laboratory stressors. Digitized cardiovascular data being collected include EKG, Impedance Cardiogram (ICG), phonocardiogram, and a peripheral pulse wave measure. Blood pressure readings are also being collected and stored on disk. The computer presents three challenging video games, each designed to elicit cardiovascular reactions. Processing programs are being used and developed for the standardized scoring of the digitized signals. To assist in epidemiological research a mobile testing unit has been assembled for the easy administration of the test battery in varying geographical locations. The test battery being developed will increase the feasibility of epidemiological and clinical assessment of stress-induced cardiovascular responses which may substantiate a link between reactivity and cardiovascular disease.     

Invasive and noninvasive techniques for analysis of cardiovascular effects of sleep apnea]

There is increasing epidemiological and experimental evidence that Sleep Disordered Breathing (SDB) is associated with cardiovascular disease such as hypertension, ischaemic heart disease, heart failure and stroke. Due to the high prevalence of SDB in the general population (5% to 10%) there is increasing demand for cost-effective and reliable diagnostic tools for the assessment of cardiovascular function during sleep in patients with SDB. The first part of this review focuses on our present knowledge about the association between SDB and cardiovascular disease. In the second part various methods for the assessment of cardiac function, blood pressure, sympathetic activity, as well as vascular and cerebrovascular function in patients with SDB are discussed. Current developments such as ECG analysis for SDB screening or arterial tonometry are introduced. Further improvements in the diagnostic tools for the investigation of cardiovascular function in patients with SDB may to advantage be coupled with epidemiological studies. This approach may demonstrate the predictive value or superiority of a specific diagnostic parameter in the diagnosis of SDB and its cardiovascular consequences.     

Arsenic in the aetiology of cancer

Arsenic, one of the most significant hazards in the environment affecting millions of people around the world, is associated with several diseases including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater contamination by arsenic is the main route of exposure. Inhalation of airborne arsenic or arsenic-contaminated dust is a common health problem in many ore mines. This review deals with the questions raised in the epidemiological studies such as the dose-response relationship, putative confounders and synergistic effects, and methods evaluating arsenic exposure. Furthermore, it describes the metabolic pathways of arsenic, and its biological modes of action. The role of arsenic in the development of cancer is elucidated in the context of combined epidemiological and biological studies. However, further analyses by means of molecular epidemiology are needed to improve the understanding of cancer aetiology induced by arsenic.     

Epidemiology, cancer genetics and microarrays: making correct inferences, using appropriate designs

Different disciplines approach cancer with different study designs, techniques and established bodies of knowledge. This article identifies some established epidemiological data and methods, which are useful for cross-disciplinary molecular and genetic studies of cancer but which are ignored by some researchers. First, the international variation in cancer risk is accounted for extensively by variation in environmental exposures; it is unlikely that even minute characterization of individual genomes will provide the best assessment of cancer risk in the absence of comparably detailed information on the environment. Second, epidemiological study-design methods are sometimes the most appropriate to answer molecular questions, particularly when using techniques such as expression microarrays or proteomics to establish differences among cancer subtypes or biomarkers in the setting of a non-experimental study. In such studies, it is essential to avoid bias, control confounding and undertake accurate replication. Established epidemiological data and methods will contribute to the best use of the new molecular technology.     

Polyphenols and prevention of cardiovascular diseases

PURPOSE OF REVIEW: Polyphenols are the most abundant dietary antioxidants and research on their role in the prevention of degenerative diseases has developed quickly over these last few years. This paper reviews the recent studies on the prevention of cardiovascular diseases by polyphenols, focusing on human studies. RECENT FINDINGS: A large number of recent intervention studies have shown that several biomarkers of cardiovascular risk are influenced by the consumption of polyphenol-rich foods. Effects on biomarkers of oxidative stress, lipemia and inflammation appear so far inconclusive. More consistent effects have been observed on endothelial function and haemostasis and support a reduction of risk by polyphenols in agreement with the few epidemiological studies already published. All clinical studies have used foods or beverages containing a mixture of different polyphenols and the exact nature of the most active compounds remains largely unknown. Absorption, metabolism and elimination vary widely between polyphenols. These data on bioavailability should be taken into account to improve the experimental design and the interpretation of the observed effects. SUMMARY: Future intervention studies should include a detailed assessment of the bioavailability of polyphenols. Beyond clinical trials carried out with polyphenol-rich foods, more studies with pure polyphenols will also be needed to establish their role in the prevention of cardiovascular diseases.     

Cholesteryl ester transfer protein: the controversial relation to atherosclerosis and emerging new biological roles

Cholesteryl ester transfer protein (CETP) exerts a profound impact on high-density lipoprotein (HDL) metabolism and, consequently, on the risk of atherosclerosis development and cardiovascular mortality. Here, we review the complex relationship between CETP and atherosclerosis based upon the experimental, clinical, and epidemiological studies. In addition, we discuss the recent findings that expand the functions of CETP to new areas of interest such as Alzheimer's disease, inflammation, and obesity.     

Mercury as a risk factor for cardiovascular diseases

Mercury is a heavy metal that exists naturally in the environment. Major sources include the burning of fossil fuels (especially coal) and municipal waste incineration. Mercury can exist in several forms, with the most hazardous being organic methylmercury. In waterways (lakes, rivers, reservoirs, etc.), mercury is converted to methylmercury, which then accumulates in fish, especially in large predatory fish. Fish and fish products are the major--if not the only--source of methylmercury in humans. Mercury has long been recognized as a neurotoxin for humans, but in the last 10 years, its potentially harmful effects on cardiovascular diseases (CVD) have raised a cause for concern, mostly due to the proposed role of mercury in oxidative stress propagation. Some epidemiological studies have indeed found an association between increased levels of mercury in the body and risk of CVD. There are several plausible mechanisms to explain the association; these are discussed in this review. We also review the epidemiological studies that have investigated the association between mercury and CVD.     

Special feature for the Olympics: effects of exercise on the immune system: overview of the epidemiology of exercise immunology

The application of epidemiological methods to exercise immunology is reviewed briefly, with particular reference to the possible influences of physical activity, exercise and training on susceptibility to upper respiratory infections. Available reports are arbitrarily rated in terms of limiting factors: the quality of the assessment of physical activity, the precision of diagnosis of upper respiratory infection and overall methodology. The pattern of physical activity has often been clearly established but, in part because of the problems associated with the competitive environment, assessments of infection and overall methodology have often been less than optimal. Although there is some evidence that susceptibility to infection is increased by either a single bout of very heavy activity or a period of heavy training, reports are far from unanimous, and in certain respects fail to meet the classical epidemiological criteria of a causal relationship. The issue is important to both the health and the success of the international competitor, and merits definitive investigation, using optimal methods to assess both activity patterns and infection.     

Nutrients: the environmental regulation of cardiovascular gene expression

The complexity of nutrient-gene interactions has led to the development of a new branch in the nutrition sciences, the nutrigenomics. The individual susceptibility to nutrients based on environment --> genotype --> phenotype interplay makes this new research field extremely promising although complex. In this review, we highlight and examine recent findings and the most relevant hypotheses on the role of the diet in the onset and progression of cardiovascular diseases. The effect of unbalanced diets on the cardiovascular system is considered one of the most important risk factors both for ischemic and degenerative myocardial pathologies. The concept that nutrigenomics could help in improving public and personal health is becoming tangible indicating future directions for basic and applied research in the pathophysiology of cardiovascular disease.     

Review and meta-analysis of epidemiological associations between low/moderate doses of ionizing radiation and circulatory disease risks, and their possible mechanisms

Although the link between high doses of ionizing radiation and damage to the heart and coronary arteries has been well established for some time, the association between lower-dose exposures and late occurring cardiovascular disease has only recently begun to emerge, and is still controversial. In this paper, we extend an earlier systematic review by Little et al. on the epidemiological evidence for associations between low and moderate doses of ionizing radiation exposure and late occurring blood circulatory system disease. Excess relative risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well-known (but unobserved) risk factors, and there is statistically significant (p < 0.00001) heterogeneity between the risks. This heterogeneity is reduced, but remains significant, if adjustments are made for the effects of fractionated delivery or if there is stratification by endpoint (cardiovascular disease vs. stroke, morbidity vs. mortality). One possible biological mechanism is damage to endothelial cells and subsequent induction of an inflammatory response, although it seems unlikely that this would extend to low-dose and low-dose-rate exposure. A recent paper of Little et al. proposed an arguably more plausible mechanism for fractionated low-dose effects, based on monocyte cell killing in the intima. Although the predictions of the model are consistent with the epidemiological data, the experimental predictions made have yet to be tested. Further epidemiological and biological evidence will allow a firmer conclusion to be drawn.     

'Alzheimer-like' pathology in a murine model of arterial hypertension

Genetic AD (Alzheimer's disease) accounts for only few AD cases and is almost exclusively associated with increased amyloid production in the brain. Instead, most patients are affected with the sporadic form of AD and typically have altered clearance mechanisms. The identification of factors that influence the onset and progression of sporadic AD is a key step towards understanding its mechanism(s) and developing successful therapies. An increasing number of epidemiological studies describe a strong association between AD and cardiovascular risk factors, particularly hypertension, that exerts detrimental effects on the cerebral circulation, favouring chronic brain hypoperfusion. However, a clear demonstration of a pathophysiological link between cardiovascular risk factors and AD aetiology is still missing. To increase our knowledge of the mechanisms involved in the brain's response to hypertension and their possible role in promoting amyloid deposition in the brain, we have performed and investigated in depth different murine models of hypertension, induced either pharmacologically or mechanically, leading in the long term to plaque formation in the brain parenchyma and around blood vessels. In the present paper, we review the major findings in this particular experimental setting that allow us to study the pathogenetic mechanisms of sporadic AD triggered by vascular risk factors.     

Progestins in the menopause

While the benefits of progestin use in hormone replacement therapy (HRT) are well recognised as far as endometrial protection is concerned, their risks and drawbacks have generated controversial articles. The data related to the progestin effect on breast tissue has been interpreted differently from country to country. However it has been admitted that, according to the type of progestin used, the dose and duration of its application, a predominant antiproliferative effect is observed in the human breast cells. As far as breast cancer risk is concerned, most epidemiological studies do not suggest any difference between the estrogens given alone or combined to progestins in HRT. When the cardiovascular risk factors are considered, some molecules with a higher androgenic potency than others, attenuate the beneficial effects of estrogens on the lipid profile and the vasomotion as well. On the other hand, other progestins devoid of androgenic properties do not exert these deleterious effects. The epidemiological data does not suggest any negative effect of the progestins administered together with estrogens on cardiovascular morbidity or mortality.

However, recent results suggest that in women with established coronary heart disease (CHD), HRT may not protect against further heart attacks, when the progestin selected possesses androgenic properties.

Complying with the classic contra indications of HRT and selecting molecules devoid of estrogenic, androgenic, or glucocorticoid effect should allow a larger use of the progestins without any major drawback.     

Understanding cardiovascular physiology in zebrafish and Xenopus larvae: the use of microtechniques

Zebrafish and Xenopus, genetically accessible vertebrates with an externally developing, optically clear embryo, are ideally suited for in vivo functional dissection of the embryonic development of the circulatory system. Physiological characterizations of the cardiovascular system are still imperative for a more complete understanding of the connections between genetic/epigenetic factors and cardiovascular development. Here, we review experimental tools and methods that have been developed to measure numerous cardiovascular parameters in these millimetre-sized animals.     

Electromagnetic field in and around the campus of Jawaharlal Nehru University, New Delhi

We have surveyed the levels of magnetic field in the open environment around the high-tension lines as well as in the domestic and laboratory environment in the JNU campus. Measurements were made in the direction of most likely access, and from the surface of the appliances. The data so obtained are analyzed and compared with some quoted in the literature. It is hoped that the results will be useful for epidemiological studies in determining the criteria for safe human exposure.     

Carotenoids and cardiovascular disease: what research gaps remain?

PURPOSE OF REVIEW: Dietary and blood carotenoids, including alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin, have been examined in a number of epidemiological studies in recent years for the risk of cardiovascular disease. This review assimilated the existing and recent literature on carotenoids and cardiovascular disease and considered what research gaps may remain. RECENT FINDINGS: Numerous large cohort studies have been published in largely American men and women that have examined dietary intake or blood levels of total or individual carotenoids with the risk of various cardiovascular endpoints. Overall, early, promising results have grown increasingly inconsistent over time. More recently, studies examining lycopene and lutein/zeaxanthin have offered more promising data on a possible, but not yet established, inverse association with the risk of cardiovascular disease. Recent epidemiological data on beta-cryptoxanthin and cardiovascular disease are lacking. Primary and secondary prevention trials have extensively examined beta-carotene, but not other carotenoids, for the risk of cardiovascular disease as either the primary or secondary endpoint with largely null results. More recent studies have focused on individual carotenoids in relation to cardiovascular disease and require a more careful evaluation of potential mechanisms of effect. SUMMARY: The promise of early epidemiological studies on carotenoids and cardiovascular disease paved the way to largely disappointing results from several large prevention trials of beta-carotene. Emerging recent evidence of potential cardioprotective effects for lycopene and other carotenoids besides beta-carotene in the diet and blood suggest that there is more to be learned in the story of carotenoids and both atherosclerotic progression and clinically manifested cardiovascular disease.     

C-reactive protein as a risk factor versus risk marker

PURPOSE OF REVIEW: C-reactive protein (CRP) is consistently associated with cardiovascular disease in prospective and cross-sectional clinical and epidemiological studies. Inflammation is an important mechanism in cardiovascular disease, and the plasma level of CRP is considered to reflect the inflammatory condition of the patient and/or the vessel wall. In addition, there are also a number of indications for a causal role of CRP in cardiovascular disease. RECENT FINDINGS: A number of new publications show potential causal effects of CRP on cardiovascular disease, and evidence from human-CRP transgenic animals also indicates a causal contribution of CRP to cardiovascular disease. On the other hand, a new large prospective study and an updated meta-analysis indicate that the contribution of CRP to cardiovascular disease is less impressive than reported earlier (odds ratio, 1.58; 95% confidence interval, 1.48-1.68). SUMMARY: We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.     

Decreased overall virulence in coinfected hosts leads to the persistence of virulent parasites

Multiple infections are known to affect virulence evolution. Some studies even show that coinfections may decrease the overall virulence (the disease-induced mortality of a coinfected host). Yet, epidemiological studies tend to overlook the overall virulence, and within-host models tend to ignore epidemiological processes. Here, I develop an epidemiological model where overall virulence is an explicit function of the virulence of the coinfecting strains. I show that in most cases, a unique strain is evolutionarily stable (in accordance with the model I use here). However, when the overall virulence is lower than the virulence of each of the coinfecting strains (i.e., when coinfections decrease virulence), the evolutionary equilibrium may be invaded by highly virulent strains, leading to the coexistence of two strains on an evolutionary timescale. This model has theoretical and experimental implications: it underlines the importance of overall virulence and of epidemiological feedbacks on virulence evolution.     

Effect of maternal undernutrition in early gestation on ovine fetal blood pressure and cardiovascular reflexes

Human epidemiological and animal experimental studies suggest that maternal undernutrition during pregnancy may alter cardiovascular development of the offspring. The extent to which these effects involve changes in fetal cardiovascular function and whether they are necessarily linked to reduced fetal growth is unknown. In sheep, we investigated the effect of a 15% reduction in maternal global nutrition for the first 70 days of gestation (term = 147 days) on fetal blood pressure development, baroreflex control of fetal heart rate (FHR), and cardiovascular responses to acute hypoxemia in late gestation. Basal mean arterial pressure (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and rate-pressure product (P < 0.001) were significantly lower in fetuses of nutritionally restricted ewes (R) compared with controls (C). FHR was not altered. The operating point for the fetal baroreflex was significantly lower in R fetuses compared with C (P < 0.01), but there was no difference between the groups in the cardiovascular response to hypoxemia. We conclude that mild maternal undernutrition alters fetal cardiovascular development, producing low blood pressure and resetting of baroreflex control mechanisms. This effect occurs without any changes in fetal growth or blood gas status.     

Avances en el tratamiento de la hipercolesterolemia

Numerous epidemiological and prospective studies have shown a direct relationship between total cholesterol and low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (cardiovascular morbidity and mortality). In many intervention studies with more than 100,000 subjects, statins have shown a powerful and significant reduction of cardiovascular events and a decrease in cardiovascular and overall mortality, far superior to those produced by any other lipid-lowering group.Consequently statins are considered to be safe and well tolerated and are the first choice in the treatment of hypercholesterolemia and in cardiovascular disease prevention. If targets are not reached, other pharmacological groups must be associated (resins, nicotinic acid, ezetimibe, fibrates, etc.). Moreover, when hypercholesterolemia is associated with low concentrations of high-density lipoprotein (HDL)-cholesterol and high triglyceride levels, the association of statins with nicotinic acid, fibrates or omega-3 should be considered.Some questions remain to be answered: what LDL-C levels are desirable in secondary prevention? Which individuals might benefit from treatment in primary prevention? Which lipid-lowering drug is the most suitable to combine with statins and diminish cardiovascular risk in each situation? The present article reviews these important points.     

Contractility assessment in enzymatically isolated cardiomyocytes

The use of enzymatically isolated cardiac myocytes is ubiquitous in modern cardiovascular research. Parallels established between cardiomyocyte shortening responses and those of intact tissue make the cardiomyocyte an invaluable experimental model of cardiac function. Much of our understanding regarding the fundamental processes underlying heart function is owed to our increasing capabilities in single-cell stimulation and direct or indirect observation, as well as quantitative analysis of such cells. Of the many important mechanisms and functions that can be readily assessed in cardiomyocytes at all stages of development, contractility is the most representative and one of the most revealing. The purpose of this review is to provide a survey of various methodological approaches in the literature used to assess adult and neonatal cardiomyocyte contractility. The various methods employed to evaluate the contractile behavior of enzymatically isolated mammalian cardiac myocytes can be conveniently divided into two general categories??those employing optical (image)-based systems and those that use transducer-based technologies. This survey is by no means complete, but we have made an effort to include the most popular methods in terms of reliability and accessibility. These techniques are in constant evolution and hold great promise for the next generation of breakthrough studies in cell biology for the prevention, treatment, and cure of cardiovascular diseases.