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Prevention of coronary heart disease. Part II. Secondary prevention, detection of subclinical disease, and emerging risk factors.

The prevention of CHD should be a major priority among primary care physicians and subspecialists who have any dealing with the cardiovascular system. There is ample evidence from epidemiologic studies for the impact of specific risk factors on CHD events. There is also ample evidence from observational studies and clinical trials that interventions of lifestyle and pharmacologic therapy can decrease morbidity and mortality from CHD before or after the first event. It behooves the physician who wishes to practice good medicine to understand the pathophysiologic roles of the risk factors and the evidence from epidemiologic studies and clinical trials for their association with cardiovascular disease. It is important to determine the efficacy of interventions, both lifestyle and pharmacologic, in modifying CHD risk. To be effective in doing so, the practicing physician has to have the motivation to determine target goals for risk factor modification in each patient, to understand the patient's own motivations in modifying risk factors, and to define clearly with the patient the expectations of such interventions. Although there are guidelines for risk factor modification in modification of cholesterol and in hypertension, the periodic renewal of these guidelines reflects the changing concepts of risk and its modification. A cardiovascular risk factor intervention categorization is presented in Table 12. The physician must be convinced that such intervention is beneficial to the patient, cost-effective, and thus fulfills the expectations of medical practice. The practice of medicine in the evaluation and treatment of coronary heart disease has always been challenging and stimulating. The prevention of CAD disease should ultimately provide the greatest accomplishment.

Age Factors↗

Diet and cancer of the large bowel.

The incidence of large bowel cancer correlates internationally with the consumption of fat, protein or meat. Etiological hypotheses have been proposed, suggesting that a high-fat diet is related to an increased risk of large bowel cancer, while dietary fiber is claimed to have a modifying effect. However, while these hypotheses were derived from the analysis of the geographical distribution of colon cancer in humans, they are not unequivocally supported by the results of further epidemiological studies. This is particularly true for case-control studies which generally have not confirmed an association between diet and the risk of colorectal cancer at the individual level. Lack of uniformity among the findings of epidemiological studies concerned with the role of diet in the etiology of bowel cancer could be explained by 1. lack of sensitive and reproducible methods for assessment of diet in epidemiological studies, 2. lack of knowledge of the mode of action of dietary factors responsible either for the development of the tumor or for protection against it. Future epidemiological research on diet and large bowel cancer should deal with more precisely defined hypotheses in which the possible multifactorial nature of this tumor would be taken into account.

Age Factors↗

Ten years of freedom from smallpox: lessons and experiences. Dedicated to the tenth anniversary of worldwide freedom from smallpox.

Many lessons and experiences were learned during the global programme of smallpox eradication, the most important being those which could be generalized and applied to other health programmes. This does not mean imitating or implementing smallpox eradication techniques to other diseases, since each infection requires its own strategy. It is difficult to dissect out the single key element or to equate the various factors responsible for the success, as these always worked together, in combination, depending one on others. For global eradication, the element of essential importance was international cooperation and close coordination of activities between nations. This would be impossible without proper mechanisms dedicated to international cooperation in the field of health, provided by the World Health Organization, which also assured mobilization of world resources for national programmes and application of appropriate techniques across international borders. The established specific, practical and measurable goals, objectives and targets made every programme worker clearly understand what was to be accomplished and to find his own role in achieving these objectives. Operational techniques had to be flexible, modified appropriately from country to country to make them suitable to present epidemiological situations, local administrative and health structures as well as to demographic and geographic patterns. It was the effective system of surveillance and outbreak-containment that ultimately proved to have been the key to eradication. However, application of skillful management, sound epidemiological principles, advanced technology and adequate logistic support contributed significantly to the achievement of the final goal.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

The effect of culture conditions on the in-vitro adherence of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant isolates of Staphylococcus aureus (MRSA) were divided on the basis of their epidemiologic behaviour into two subgroups, epidemic MRSA (EMRSA) and sporadic MRSA (SMRSA) strains. An existing adherence assay was modified to determine differences in adherence properties between these two groups of MRSA, and the influence of culture conditions on the adherence of SMRSA and EMRSA strains to plastic, human collagen I (HuCol I) and pharyngeal carcinoma Detroit 562 cells (D562) was determined. In-vitro parameters, such as culture medium, growth temperature and growth phase of the bacterium, influenced the adherence of MRSA strains to plastic significantly. Even more pronounced differences in adherence due to changes in growth conditions and growth phase of the bacteria were found for the adherence of MRSA strains to HuCol I. Growth phase had a significant effect on the adherence of MRSA strains to the pharyngeal carcinoma cells D562. However, the study did not find conditions which made it possible to distinguish EMRSA from SMRSA strains. These data show that extrapolation of in-vitro data concerning adherence of MRSA strains to in-vivo conditions should be treated with caution.

Bacterial Adhesion↗

Pulmonary inflammatory response to inhaled ultrafine particles is modified by age, ozone exposure, and bacterial toxin.

Epidemiological studies demonstrate associations between increasing levels of ambient particles and morbidity in the elderly with cardiopulmonary disease. Such findings have been challenged partly because particles may not act alone to cause these effects. We hypothesized that carbonaceous ambient ultrafine particles and ozone can act together to induce greater oxidative stress and inflammation in the lung than when administered alone and that these effects would be amplified in the compromised, aging lung. Two models of a compromised lung were used: endotoxin priming and old-age emphysema (TSK mice). Young (10 wk) and old (22 mo) male F344 rats and male TSK mice (14-17 mo) were exposed to ultrafine carbon particles (count median diameter 25 nm, 110 micrograms/m3) and to ozone (1 ppm) alone and in combination for 6 h. Inhalation of low-dose endotoxin (70 and 7.5 units estimated alveolar deposited dose in rats and mice, respectively) was used to model respiratory-tract infection. Cellular and biochemical lavage parameters and oxidant release from lung lavage cells were assessed 24 h after exposure. Inflammatory cell influx into the alveolar space was observed for both species and age groups: The combination of inhaled ultrafine carbon and ozone after endotoxin priming resulted in the greatest increase in lavage-fluid neutrophils. In general, the unstimulated and stimulated release of reactive oxygen species (ROS) from lavage inflammatory cells correlated well with the neutrophil response. There were significant effects of carbon particles as well as a consistent interaction between carbon and ozone as determined by analysis of variance (ANOVA). However, this interaction was in the opposite direction in young rats versus old rats and old TSK mice: Carbon and ozone interacted such that ROS activity was depressed in young rats, whereas it was enhanced in old rats and old TSK mice, indicating age-dependent functional differences in elicited pulmonary inflammatory cells. These results demonstrate that ultrafine carbonaceous particles inhaled for short periods of time can induce significant pulmonary inflammation and oxidative stress that are modified by age, copollutants, and a compromised respiratory tract.

Administration, Inhalation↗

Combined effects of dietary fat and birth weight on serum cholesterol concentrations: the Hertfordshire Cohort Study.

BACKGROUND: Blood cholesterol responses to the manipulation of dietary fat vary widely between persons. Although epidemiologic evidence suggests that prenatal growth and nutrition influence adult cholesterol homeostasis, whether prenatal growth modifies the association between dietary fat intake and serum cholesterol concentration in adults is unknown. OBJECTIVE: The aim was to examine the relation between fat intake and serum cholesterol concentrations in men and women whose birth weights were known. DESIGN: We studied a cohort of men and women aged 59-71 y. Diet was assessed with a food-frequency questionnaire. Total, HDL-, and LDL-cholesterol concentrations and the ratio of HDL to LDL cholesterol were measured in fasting blood samples from 574 men and 562 women who did not have coronary heart disease. RESULTS: Total and saturated fat intakes were not associated with serum cholesterol concentrations in men or women. However, subdivision by birth weight showed associations in men but not in women. High intakes of total and saturated fat were associated with reduced HDL-cholesterol concentrations in men with birth weights < or =3.2 kg (7 lb) but not in men with higher birth weights. Similar effects on the HDL-to-LDL cholesterol ratio were observed (P for interaction = 0.02 for total fat and 0.01 for saturated fat). When 32 men taking cholesterol-lowering medication were excluded, the interactions were strengthened (P = 0.008 and 0.006, respectively). CONCLUSION: The adverse effects of high intakes of total and saturated fat on serum cholesterol concentrations in men may be confined to those with lower birth weights.

Aged↗

Variation and modifying factors of the exposure to lead and cadmium based on an epidemiological study.

Exposure to cadmium and lead was studied using a dietary survey. Data for 1348 individuals aged 25-64 years were collected using 3-day food records. In addition to the dietary intake of heavy metals, the effect of the following were also analyzed: smoking frequency, place of residence, occupation and age. Total cadmium and lead exposure was estimated by calculating intake from food plus that from inhalation, i.e. from urban air and smoking. Heavy smoking increased the cadmium exposure three-fold. The distribution curve of total cadmium exposure was bimodal due to the additional exposure caused by smoking. The distribution curve of the lead and cadmium exposure from food was also skewed, being mostly influenced by food intake. Contaminated urban air slightly increased the total exposure to lead. Occupation had a minor effect on the exposure to both metals. Housewives and retired persons were the least exposed groups. The distribution pattern and wide range of heavy metal exposure should be taken into account in risk assessment for contaminants in food. The additional exposure to cadmium and lead from smoking and from air and water should be considered.

Adult↗

[Evolution of populations of ticks (Ixodidae and Argasidae) in relation to artificialization of the environment in the French Alps. Epidemiologic effects].

The results presented in this study are based on observations made during some 10 years in the French Alps and their surroundings. Forest clusters, as they still cover comparatively large areas, are considered the most favorable foci for several Ixodid species. Recent studies, however, have shown that environment modified by man also harbours large populations of ticks. The spreading of certain species around and even into cities is actually taking place. The following categories of tick species may be distinguished with reference to the artificialization process of the environment: 1. species occurring mainly in forest areas (Ixodes ricinus, I. trianguliceps); 2. species occurring in agricultural, suburban and preurban areas (Dermacentor reticulatus, Rhipicephalus turanicus); 3. species found in either natural wholes, burrows etc. or in constructions amidst rural areas (I. hexagonus, I. canisurga, R. pusillus); 4. species present exclusively in buildings, in either rural or urban areas (R. sanguineus, Argas reflexus). The vectorial role of the various tick species is discussed with regard to the artificialisation process. Particular attention is drawn to the appearance of new, and the extension of previously known foci of disease transmission in the vicinity of large cities.

Adaptation, Physiological↗

Associations between criteria air pollutants and asthma.

The evidence that asthma is increasing in prevalence is becoming increasingly compelling. This trend has been demonstrated not only in the United States, but also in the United Kingdom, New Zealand, Australia, and several other Western countries. In the United States, the increase is largest in the group under 18 years of age. There is mounting evidence that certain environmental air pollutants are involved in exacerbating asthma. This is based primarily on epidemiologic studies and more recent clinical studies. The U.S. Clean Air Act of 1970 provides special consideration to the class of outdoor air pollutants referred to as criteria pollutants, including O3, sulfur dioxide (SO2), particulate matter (PM), NOx, CO, and Pb. Standards for these pollutants are set by the U.S. Environmental Protection Agency with particular concern for populations at risk. Current evidence suggests that asthmatics are more sensitive to the effects of O3, SO2, PM, and NO2, and are therefore at risk. High SO2 and particulate concentrations have been associated with short-term increases in morbidity and mortality in the general population during dramatic air pollution episodes in the past. Controlled exposure studies have clearly shown that asthmatics are sensitive to low levels of SO2. Exercising asthmatics exposed to SO2 develop bronchoconstriction within minutes, even at levels of 0.25 ppm. Responses are modified by air temperature, humidity, and exercise level. Recent epidemiologic studies have suggested that exposure to PM is strongly associated with morbidity and mortality in the general population and that hospital admissions for bronchitis and asthma were associated with PM10 levels. In controlled clinical studies, asthmatics appear to be no more reactive to aerosols than healthy subjects. Consequently, it is difficult to attribute the increased mortality observed in epidemiologic studies to specific effects demonstrated in controlled human studies. Epidemiologic studies of hospital admissions for asthma have implicated O3 as contributing to the exacerbation of asthma; however, most study designs could not separate the O3 effects from the concomitant effects of acid aerosols and SO2. Controlled human clinical studies have suggested that asthmatics have similar changes in spirometry and airway reactivity in response to O3 exposure compared to healthy adults. However, a possible role of O3 in worsening atopic asthma has recently been suggested in studies combining allergen challenge following exposure to O3. Attempts at identification of factors that predispose asthmatics to responsiveness to NO2 has produced inconsistent results and requires further investigation. In summary, asthmatics have been shown to be a sensitive subpopulation relative to several of the criteria pollutants. Further research linking epidemiologic, clinical, and toxicologic approaches is required to better understand and characterize the risk of exposing asthmatics to these pollutants.

Adolescent↗

Effect of treatment of chronic periodontitis on levels of serum markers of acute-phase inflammatory and vascular responses.

AIMS: Recent epidemiological work suggests an association between periodontal disease severity and cardiovascular disease risk. This study aimed to ascertain if circulating levels of cardiovascular and systemic inflammatory markers could be modified following treatment of periodontal disease. METHOD: Adult subjects were recruited from those awaiting periodontal treatment and randomised to either immediate (test, n=24) or delayed treatment (control, n=15). Demographic and clinical data were collected and venous blood was taken before and either 6 weeks after completion of treatment or after an equivalent 3-month control period. Periodontal examination included probing depth, loss of attachment, plaque scores and bleeding scores. Blood was analysed to determine serum and plasma fibrinogen, C-reactive protein, sialic acid, tumour necrosis factor-alpha and interleukin -6 and -1beta. Effects of treatment were assessed by paired tests and analysis of variance by treatment group with baseline covariates. RESULTS: Treatment improved plaque and bleeding scores and reduced probing depths (p<0.002). However, there were no statistically significant changes in levels of any of the systemic markers. CONCLUSION: Improvement in periodontal health did not influence the levels of vascular markers.

Acute-Phase Proteins↗

The potential for oxytocin (OT) to prevent breast cancer: a hypothesis.

This hypothesis proposes that carcinogens in the breast are generated by the action of superoxide free radicals released when acinal gland distension, under the influence of unopposed prolactin, causes microvessel ischaemia. Inadequate nipple care in the at-risk years leads to ductal obstruction preventing the elimination of carcinogens from the breast. The regular production of oxytocin (OT) from nipple stimulation would cause contraction of the myoepithelial cells, relieving acinal gland distension and aiding the active elimination of carcinogenic fluid from the breast. Mechanical breast pump stimulation causes an increase in plasma OT levels in the luteal but not in the follicular phase of the menstrual cycle. OT production upon nipple stimulation in the luteal phase of premenopausal, non-lactating women may be protective against the high rates of mitotic breast cell division noted at this time via the potential to block the effect of oestrogen. The epidemiology of breast cancer suggests that lengthy lactation time is beneficial. Sexual activity in nulliparous women also protects and OT levels have been shown to rise with orgasm in women and in men. OT systems in the brain are intricately linked to oestrogen and progesterone levels, and it is possible that these hormones may modify the OT secretory response both centrally and through an effect on the sensitivity of the breast. OT production with nipple care and in sex and lactation, and the reduction in cycling ovarian hormones that occurs with pregnancy, may all be important preventative factors in the development of breast cancer both pre- and post-menopausally.

Breast Neoplasms↗

The hepatitis B virus.

Of all the hepatotropic viruses, HBV is associated with the greatest worldwide morbidity and mortality. This is because of the ease of transmission and the potential for progression to a chronic infective carrier state, with the complications of cirrhosis and hepatocellular carcinoma. The use of PCR has shown that some of the earlier concepts concerning the interpretation of serological data were inaccurate. Many patients with anti-HBe and anti-HBs have viral DNA detectable by PCR, and some hepatocellular carcinoma patients have detectable HBV DNA in their livers in the absence of all serological markers of HBV disease. The clearance of HBV infected cells from the liver is dependent on the interplay between the interferon system and the cellular limb of the host immune response. The importance of the nucleocapsid proteins as targets for sensitized cytotoxic T cells has been established for chronic HBV infection. The importance of pre-S sequences as inducers and targets of the virus-neutralizing humoral immune response is becoming established, but their precise role must await the development of in vitro models of hepadnavirus infection and a greater understanding of the mechanisms of viral uptake. The epidemiology and clinical course of the disease can be modified by immunization, immune stimulation and antiviral chemotherapy. For the developing world, a programme of immunization at birth would be the most effective way of eliminating this disease, but at present the cost is prohibitive. For the developed world, immunization is realistic for the at-risk population, and anti-viral and immunostimulatory therapy available for those already infected. In adult acquired chronic HBV infection alpha-interferon produces HBe antigen clearance in 40-60% of cases and is followed by resolution of the hepatic inflammation. Results in neonatally acquired infection are less impressive and prednisolone priming followed by interferon may be needed. The presence of a mutation in the pre-core region of some virus isolates has recently been described. Hepatocytes infected with this virus cannot produce HBe antigen and the course of the liver disease is fairly rapid. Whether this mutant causes liver damage in the same way as the wild virus or is directly cytopathic remains unclear, and its relationship to fulminant hepatitis is under investigation.

Adolescent↗

Genetic dissection of familial autoimmune thyroid diseases using whole genome screening.

The autoimmune thyroid diseases (AITDs) are multifactorial disease which are caused by genetic susceptibility and environmental triggers. Various epidemiological and genetic techniques can be employed to study the genetic contribution to disease development. Most epidemiologic data support an important genetic contribution to the development of AITD. The genetic susceptibility to AITD involves several genes with varying effects. Some AITD susceptibility genes are most likely immune modifying genes which increase the susceptibility to autoimmunity in general (e.g. HLA, CTLA-4) while others may be thyroid-specific (e.g. thyroglobulin). These genes probably act in concert to increase the autoimmune reactions in susceptible individuals and direct them towards the thyroid.

Abatacept↗

Depressive symptoms, cognitive decline, and risk of AD in older persons.

BACKGROUND: Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD, but there have been few prospective studies and their results have been inconsistent. METHODS: Participants are Catholic clergy members who were aged > or =65 years and who did not have clinical evidence of AD. During a 7-year period, they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived. Number of depressive symptoms was assessed at baseline with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The association of CES-D score with incident AD, using proportional hazards models, and cognitive decline, using random effects models, was examined. RESULTS: At baseline, participants reported an average of about one depressive symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108 persons developed AD. In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function, CES-D score was associated with both risk of AD and rate of cognitive decline. For each depressive symptom, risk of developing AD increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. CONCLUSIONS: The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD.

Aged↗

Airborne particles are a risk factor for hospital admissions for heart and lung disease.

We examined the association between particulate matter [less than/equal to] 10 microm; (PM(10)) and hospital admission for heart and lung disease in ten U.S. cities. Our three goals were to determine whether there was an association, to estimate how the association was distributed across various lags between exposure and response, and to examine socioeconomic factors and copollutants as effect modifiers and confounders. We fit a Poisson regression model in each city to allow for city-specific differences and then combined the city-specific results. We examined potential confounding by a meta-regression of the city-specific results. Using a model that considered simultaneously the effects of PM(10) up to lags of 5 days, we found a 2.5% [95% confidence interval (CI), 1.8-3. 3] increase in chronic obstructive pulmonary disease, a 1.95% (CI, 1. 5-2.4) increase in pneumonia, and a 1.27% increase (CI, 1-1.5) in CVD for a 10 microg/m(3) increase in PM(10). We found similar effect estimates using the mean of PM(10) on the same and previous day, but lower estimates using only PM(10) for a single day. When using only days with PM(10) < 50 mg/m(3), the effect size increased by [greater/equal to] 20% for all three outcomes. These effects are not modified by poverty rates or minority status. The results were stable when controlling for confounding by sulfur dioxide, ozone, and carbon monoxide. These results are consistent with previous epidemiology and recent mechanistic studies in animals and humans.

Aged↗

A retrospective study of the effect of long-term topical application of retinaldehyde (0.05%) on the development of actinic keratosis.

BACKGROUND: The role of topical retinoids on photocarcinogenesis is still unclear. Retinaldehyde is a natural metabolite of vitamin A used as a cosmetic product. Its effect on actinic keratoses has not been studied to date. OBJECTIVE: To study the incidence of actinic keratoses during long-term application of retinaldehyde in order to evaluate a possible chemoprophylactic effect. METHODS: We conducted a retrospective study on 61 patients who had applied retinaldehyde on photoexposed body areas for a period ranging from 6 to 142 months. We counted the total number of actinic keratoses and cutaneous tumors that appeared over the time of exposure to retinaldehyde. RESULTS: The epidemiological characteristics of actinic keratoses were not modified by the application of retinaldehyde. Irregular application as compared to regular application of retinaldehyde was not associated with a change in the risk of actinic keratoses, suggesting that continuous use is not associated per se with a higher risk of actinic keratoses. CONCLUSION: With the statistical power limitation of this study, retinaldehyde applied alone does not appear to have prophylactic effects on the development of actinic keratoses. The design adopted is feasible to study the safety of cosmetic products applied for a long period of time.

Administration, Topical↗

Evolving methods in genetic epidemiology. IV. Approaches to non-Mendelian inheritance.

From this overview it can be concluded that the understanding of the biologic properties and the development of analytic tools to identify repeat sequence mutations, genomic imprinting effects, and mitochondrial mutations are only beginning. Development of approaches to identify such phenomena as modifying effects or genetic components of complex traits is a new area of research. Not mentioned here are the ways in which locating a gene with such properties (i.e., linkage analysis) would be affected if such properties were not accounted for, or how to alter such analyses to obtain full information. Again, this is an exciting new area of research that will continue to motivate epidemiologists and geneticists. Hopefully, we have learned a lesson from the earlier conclusions of the studies on myotonic dystrophy: keep an open mind and never assume that the "geneticist should know best about behavior of genes".

Epidemiologic Methods↗

Molecular epidemiology of lung cancer.

Lung cancer occurs through a complex multistage process that results from the combination of carcinogen exposure and genetic susceptibilities. The primary etiology of lung cancer is tobacco smoking, but an understanding of why some smokers develop lung cancer, and others do not, remains unclear. Current studies focus on genetic susceptibilities to lung cancer, and how they modify the effects of tobacco smoke carcinogens. New assays are being developed to study other contributors to cancer risk, such as interindividual differences in DNA repair. There is current evidence to suggest that the risk of lung cancer for women, compared to men, is higher for the same level of smoking. Several biological differences for the types of lung cancer have been observed in women and men. Also, there appear to be differences in lung cancer between Caucasians and African-Americans. Molecular epidemiology tools are uniquely suited to study these biological differences. These studies will improve cancer risk assessments and focus cancer prevention strategies. Other studies also are focusing on tobacco addiction, in order to lead to improved smoking cessation strategies.

Black People↗