Syndrome X and mortality: a population-based study. Risk Factor and Life Expectancy Research Group

The present report analyzes the prevalence of the cluster of metabolic abnormalities defined as syndrome X (high blood glucose, high blood pressure, low high density lipoprotein (HDL) cholesterol, and high triglycerides) and its impact on cardiovascular disease mortality in a large cohort of men and women (22,561 men and 18,495 women). These individuals were participants in a series of epidemiologic investigations of cardiovascular disease conducted in Italy between 1978 and 1987. They were followed for an average of 7 years, during which time a total of 1,218 deaths occurred (1,003 in men and 215 in women). Deaths were coded according to the International Classification of Diseases, 9th Revision (ICD-9). The prevalence of the full cluster of metabolic abnormalities (syndrome X) was low in the population as a whole, with only 3.0 percent of men and 3.4 percent of women exhibiting the full cluster of abnormalities that comprise syndrome X. The risk of death from all causes and cardiovascular disease increased with increased numbers of metabolic abnormalities in both men and women. Mortality from cancer was significantly increased in women (but not in men) with syndrome X, compared with women with no metabolic abnormalities. Population attributable risks for all cause mortality and cardiovascular disease mortality were 0.06 and 0.09 in men and 0.04 and 0.48 in women when assessed by population cutpoints. These data from a large population-based epidemiologic investigation indicate that the presence of a full cluster of metabolic abnormalities from syndrome X is an important risk factor for cardiovascular disease and all-cause mortality in both men and women, but that the low prevalence of such a cluster in the population reduces the public health impact of syndrome X. The majority of individuals who die from cardiovascular disease present elevations in any one, two, or three of the metabolic abnormalities. The notion of the cluster of metabolic abnormalities (syndrome X) should not distract our attention from established individual risk factors that have been proven to be major causes of cardiovascular disease death and disability in our society.     

Stress and genetic testing for disease risk.

Healthy people who believe they are at risk for a life-threatening disease appear to carry a substantial stress burden because of threat of disease and uncertainty of risk. Testing for risk factors may be helpful by reducing this uncertainty, but diseases with multiple causes, like breast cancer, appear to be determined by genetic factors and by age, reproductive behavior, exposure to environmental toxins, or unknown antecedents. For diseases caused by inherited genetic defects, testing brings different benefits and stressors. A model is proposed that predicts long-term distress when risk analysis suggests a very high risk, when uncertainty is not reduced, when results of testing are at odds with preventive actions already taken, and when people who receive a positive, risk-increasing result lack strong social support, coping skills, other psychosocial resources, or all of these. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The growth law of primary breast cancer as inferred from mammography screening trials data

BACKGROUND: A potential source of bias in epidemiological studies comes from studying people at different stages of disease progression. This can result in biased selection of cases or in errors of measurement of exposures. METHODS: We use stage of disease at the time of diagnosis to evaluate how inclusion of people at different stages in the disease process can influence associations between environmental exposures and colon cancer. Data used were generated from a large case-control study of colon cancer. RESULTS: For most environmental exposures evaluated, including physical activity, body size, use of aspirin and of non-steroidal anti-inflammatory drugs, and dietary intake of folate and fibre, we did not observe differences in patterns of association by stage of disease at diagnosis. However, for total energy and red meat intake (men only), alcohol consumption, cigarette smoking, and family history of colorectal cancer among first degree relatives, patterns of associations were stronger when colon cancer was detected at an earlier stage of disease progression than when it was detected at a more advanced stage. CONCLUSIONS: Most exposures did not differ by stage of disease, thus selectively excluding cases at different disease stages should not influence associations between these exposures and colon cancer. Associations for other factors, such as alcohol consumption and cigarette smoking, may be biased from asking cases with advanced disease to recall a non-disease-free time period. Associations with family history may also be biased if those with a family history of colorectal cancer are detected at an earlier stage and therefore more likely to participate in epidemiological studies.     

Genetics of ischaemic heart disease

Coronary heart disease, especially when it affects younger individuals, tends to cluster in families. Known risk factors occur in 50-75% of patients with myocardial infarction. Yet commonly occurring risk factors are not strongly inherited, and the familial aggregation of coronary heart diseas may not be attributable to familial resemblance in serum cholesterol and blood pressure levels. Alternatively, such aggregation may be due to unknown familial risk factors. Nevertheless, screening of relatives of individuals with evident risk factors is of importance, and environmental manipulation is likely to be of value in prevention of coronary heart disease.     

More than 10 years of unrecognized nosocomial transmission of legionnaires' disease among transplant patients

OBJECTIVE: To investigate a cluster of cases of legionnaires' disease among patients at a hospital. SETTING: A university hospital that is a regional transplant center. DESIGN: Retrospective review of microbiology and serology data from the hospital laboratories and prospective surveillance via the radiology department; a case-control study and environmental sampling within the hospital and from nearby cooling towers. RESULTS: Diagnosis of seven cases of legionnaires' disease in the first 9 months of 1996 led to recognition of a nosocomial outbreak that may have begun as early as 1979. Review of charts from 1987 through September 1996 identified 25 culture-confirmed cases of nosocomial or possibly nosocomial legionnaires' disease, including 18 in bone marrow and heart transplant patients. Twelve patients (48%) died. During the first 9 months of 1996, the attack rate was 6% among cardiac and bone marrow transplant patients. For cases that occurred before 1996, intubation was associated with increased risk for disease. High-dose corticosteroid medication was strongly associated with the risk for disease, but other immunosuppressive therapy or cancer chemotherapy was not. Several species and serogroups of Legionella were isolated from numerous sites in the hospital's potable water system. Six of seven available clinical isolates were identical and were indistinguishable from environmental isolates by pulsed-field gel electrophoresis. Initial infection control measures failed to interrupt nosocomial acquisition of infection. After extensive modifications to the water system, closely monitored repeated hyperchlorinations, and reduction of patient exposures to aerosols, transmission was interrupted. No cases have been identified since September 1996. CONCLUSIONS: Legionella can colonize hospital potable water systems for long periods of time, resulting in an ongoing risk for patients, especially those who are immunocompromised. In this hospital, nosocomial transmission possibly occurred for more than 17 years and was interrupted in 1996, after a sudden increase in incidence led to its recognition. Hospitals specializing in the care of immunocompromised patients (eg, transplant centers) should prioritize surveillance for cases of legionnaires' disease. Aggressive control measures can interrupt transmission of this disease successfully.     

The contribution of epidemiology to knowledge of cancer

Epidemiology has contributed to knowledge of cancer in five ways. First, it has demonstrated that all cancers that are at all common anywhere vary in incidence from place to place and from time to time. The amount of variation is large, sometimes several hundred fold, and no cancers are so uniformly common that they would affect as many as 1 per cent of people by 75 years of age, in the absence of other causes of death, in all countries. Studies of migrant groups and the changes that have occurred with time show that this variation is, in large part, due to environmental factors and that most cancers are, in principle, preventible. Secondly it has shown that the incidence of specific cancers can be correlated with the prevalence of factors in the environment that might be suspected of causing the disease. Recent correlations include those between oesophageal cancer in Iran and the consumption of certain locally produced foods, between colon cancer and the presence of certain groups of anaerobic bacteria in the faeces, and between liver cancer and the amount of aflatoxin in the diet. These correlations do not provide direct evidence of causation, but they do suggest ideas for investigation by other methods. Thirdly, epidemiology has provided means for testing hypotheses by relating the occurrence of particular types of cancer to the personal characteristics of individuals, either by studying the past experience of people with and without cancer, or by following up people whose exposure to suspected agents has been previously defined. In this way it has been possible to detect dozens of occupational hazards in industry, which is many more than have been detected by laboratory experiment. Fourthly, epidemiology has confirmed that an agent is a cause of cancer by monitoring the effects of intervention to reduce or prevent exposure. An example is provided by observation in British doctors, who have reduced their consumption of cigarettes to half the national average and have experienced a corresponding reduction in the risk of death from cancers of the lung.     

Sclerosing cholangitis, race and sex

BACKGROUND: Primary sclerosing cholangitis develops in 3-10% of patients with ulcerative colitis, and may be associated with an increased cancer risk. Ulcerative colitis is probably less common in people of African origin than in populations of European descent. AIMS AND METHODS: To review the records of all patients under regular follow up for ulcerative colitis at St Bartholomew's Hospital (London, UK), a tertiary referral centre, prompted by discovering a cluster of cases with common features. RESULTS AND CONCLUSIONS: Among 166 patients with ulcerative colitis under regular follow up, only four (all women) are of African or Caribbean genetic origin, and three of these have developed sclerosing cholangitis within three years of presentation with colitis, compared with four of 162 patients of European or Asian descent (odds ratio 119, 95% confidence interval 8-3837; p = 0.0002). This cluster, which is not explained by common HLA DR or DQ type, suggests that Africans and Afro-Caribbeans, especially women, may be at increased risk of sclerosing cholangitis. This may reflect genetic influences on the development of enteric and hepatobiliary inflammatory disease.     

Statistical power and design of focused clustering studies

Focused clustering studies investigate raised incidence of disease in the vicinity of prespecified putative sources of increased risk. The analytic power functions of three focused tests of disease clustering are defined and used to address two design issues related to focused cluster studies. The power functions provide sample sizes required to detect a given increase in relative risk and allow measurement of the effects of aggregating data when a fixed underlying cluster model is assumed. Results are illustrated on hypothetical data as well as leukaemia data from upstate New York.     

Impact of genetic risk information and type of disease on perceived risk, anticipated affect, and expected consequences of genetic tests.

Objective: Genetic tests vary in their prediction of disease occurrence, with some mutations conferring relatively low risk and others indicating near certainty. The authors assessed how increments in absolute risk of disease influence risk perceptions, interest, and expected consequences of genetic tests for diseases of varying severity. Design: Adults (N = 752), recruited from New Zealand, Australia, and the United Kingdom for an online analogue study, were randomly assigned to receive information about a test of genetic risk for diabetes, heart disease, colon cancer, or lung cancer. The lifetime risk varied across conditions by 10% increments, from 20% to 100%. Main Outcome Measures: Participants completed measures of perceived likelihood of disease for individuals with mutations, risk-related affect, interest, and testing consequences. Results: Analyses revealed two increment clusters yielding differences in likelihood perceptions: A “moderate-risk” cluster (20%–70%), and a “high-risk” cluster (80%–100%). Risk increment influenced anticipated worry, feelings of risk, testing-induced distress, and family obligations, with nonlinear patterns including disproportionately high responses for the 50% increment. Risk increment did not alter testing interest or perceived benefits. These patterns of effects held across the four diseases. Conclusion: Magnitude of risk from genetic testing has a nonlinear influence on risk-related appraisals and affect but is unrelated to test interest. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective dopamine neurotoxicity by an industrial chemical: an environmental cause of Parkinson's disease?

While unproved, environmental toxins of industrial and or agricultural origin represent an attractive theory to explain the increasing incidence of degenerative diseases of the nervous system such as Parkinson's disease (PD). We have examined several chemicals utilized in an area of Israel previously demonstrated to contain a statistically greater than average number of people with Parkinson's disease. One of these agents, a light stabilizer employed universally in the production of polyolifins used in plastics, depleted primary mesencephalic cultures of dopamine neurons, and produced a dopamine-specific lesion of the substantia nigra pars compacta when injected stereotactically into the ventral midbrain of adult rats. The observed effects were dose-dependent. These findings represent a potentially significant development in the search for industrial/environmental causes of neurodegenerative disease.     

Fluorescent microsatellite analysis reveals duplication of specific chromosomal regions in papillary renal cell tumors

The traditional approach in epidemiology of relating exposure to an environmental agent such as a drug or infective agent has been to measure an overall risk (i.e., average and then "adjust risk for demographic variables and other confounders"). An attempt is sometimes made to define a "susceptible" subgroup. The analyses are usually based on good statistical methodology rather than an understanding of the interaction of body of host and agent. A twofold risk for 1000 exposed versus nonexposed people could be an average twofold risk for all 1000 exposed or a 20-fold risk for 100 exposed individuals (i.e., a drug-host interaction). Clearly, finding the 100 individuals with a 20-fold risk has much greater clinical importance than a twofold risk for 1000 people. The world of epidemiology may be changing-we may soon be able to define risk based on genetic susceptibility, at least sometimes.     

Epidemiological course of cardiovascular diseases in developing countries

Though the environmental and medical conditions are very different, similar population characteristics can be observed in the developing countries. The mean age of the population is young. Most people have a rural way of life, but migrations towards towns result in a disorganized urbanization and in habits more predisposing to cardiovascular diseases. Care access is often difficult for the patients. With respect to risk factors, smoking is increasing, hypertension is highly prevalent and severe, a trend towards obesity is frequent in medium or high economical level people. S or C hemoglobin diseases seem to be associated with coronary heart disease. In spite of very insufficient statistical data, it appears that: cardiovascular disease mortality is increasing when total mortality is decreasing: ischemic and hypertensive heart diseases are increasing when streptococcal or nutritional heart diseases are stabilizing or decreasing. The authors seem to be the different developing countries in respect to the crossing of these curves. Some countries have not reached the crossing. Subsaharan Africa for instance. Others have gone beyond the crossing, some Asian countries for instance. Other countries seem to be at the intersection (Mediterranean or Latin American countries). But many countries suffer the double burden of increasing and decreasing diseases. There is a general lack of prevention owing to other competing priorities and also to economical, social and educational difficulties. However in some developing countries feasibility and efficacy of preventive measures have been proved.     

Hepatic transport of the magnetic resonance imaging contrast agent gadobenate dimeglumine in the rat

In response to public concern about an increase in the incidence of leukemia among children in southwestern Sardinia (Italy), incident cases of childhood cancer (ages 0-14) were ascertained among residents in the province of Cagliari, which comprises all of southern Sardinia, in 1974-89. Completeness of the ascertainment of leukemia cases was validated by comparison with estimates derived from official statistics of mortality and survival curves. A significant excess risk of childhood acute lymphoblastic leukemia (cALL) was found for children residing in the town of Carbonia. The risk was highest in 1983-85, when seven cases occurred versus 0.8 expected. No birth-cohort effect was observed. The cALL incidence rate was significantly higher among children born and residing in Carbonia than among children born in Carbonia but residing elsewhere. However, the cALL cases did not cluster within the town of Carbonia. The proximity of the largest industrial settlement in the region of Sardinia raised the suspicion that environmental pollution was responsible for the observed excess. Information about industrial emissions from this settlement prior to the appearance of the cALL cluster was not sufficient to reject or confirm the hypothesis.     

The impact of Alzheimer disease genetics on expert and advanced gerontological nursing practice

Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the United States, affecting as many as 4 million people. Extensive research is under way to identify environmental and genetic risk factors for this complex disease. Currently, four genes are associated with an increased risk for AD: the amyloid precursor protein gene on chromosome 21, the Presenilin I gene on chromosome 14, the Presenilin II gene on chromosome 1, and the apolipoprotein E gene on chromosome 19. Expert and advanced practice gerontological nurses are faced with new challenges as a result of these gene discoveries. Gerontological nurses should assess for relevant environmental and genetic risk factors; obtain comprehensive family health histories recorded as pedigrees; integrate genetic information into diagnosis, intervention, and evaluation strategies; initiate and coordinate referrals to genetic specialists; and provide ongoing emotional and decision-making support for patients and families experiencing AD.     

Water sources and other determinants of dracunculiasis in the northern region of Ghana

This paper describes a study carried out in a rural area of Ghana on the drinking water sources and other determinants of dracunculiasis (guinea worm disease). The results confirm the association between water source choice and the prevalence of the disease. A logistic regression model was used to show the combined effect of several behavioural, biological, and environmental risk factors. The important behavioural factors were related to the head of household, fetching of water, travelling, and farming. Age was found to be an important biological risk factor for dracunculiasis, but the greatest relative risk applied to those who had suffered from guinea worm disease in the previous year. Although males were significantly more infected than females when analysing the raw data, sex did not prove to be a significant risk factor in this model. Village of residence was an important environmental risk factor for dracunculiasis. Factors related to socio-economic status were not associated with the risk of infection. The paper concludes by presenting the policy implications of the study findings.     

Lipoproteins and atherogenesis

Like many complex disease processes, atherogenesis represents the interaction of an array of genetic and environmental factors. From nonhuman animal models to the investigation of epidemiologic factors in man, no single, overriding cause for the development of this indolent vascular disease has been identified. However, the cholesterol-enriched lipoprotein particles are closely tied to the development of the disease. The genetic and environmental influences on the concentrations of specific lipoprotein subspecies provide a context for identifying patients at risk as well as for developing effective therapeutic strategies to influence and prevent the sequelae of atherogenesis.     

The problem of atopic eczema: aetiological clues from the environment and lifestyles

Atopic eczema is the most common inflammatory skin disease in children, affecting around 10% of children in the developed world. It can be a distressing condition, influencing children's well-being, personal and educational development, and family life, and it has huge economic implications for health services and individual budgets. Like other atopic diseases such as asthma and hay fever, the prevalence of atopic eczema has increased substantially over the last 30 years, for reasons largely unknown. Although a genetic predisposition to the disease has been implicated, evidence from a range of sources suggests that environmental factors play a crucial role in the disease expression. This paper reviews the epidemiology of atopic eczema, with particular attention to potential environmental aetiological factors and draws evidence from studies in the UK and internationally. First, atopic eczema has been found to vary socially and to be more prevalent in the UK among social class I and II families than among other socio-economic groups. Second, it has been suggested that cross infection from other siblings in large families may have a protective role in atopic disease expression. Third, it has been proposed that an increased risk of atopic eczema may result from decreases in helminthic infestation. Fourth, studies of migrant groups have shown large increases in disease prevalence compared with migrants' country of origin, suggesting clues as to the importance of socio-economic and environmental changes such as those associated with industrialization. Finally, a distinct and consistent geographical pattern of eczema has been observed in the UK which cannot be explained by social class distribution. The various types of study have attempted to identify reasons for differences in prevalence but, to date, no definitive causation has been identified. In some cases, specific risk factors have been suggested and include house dust mites, dietary allergens and irritants. It is argued here that the aetiology is unlikely to be simple or uni-causal and that an understanding of the relationships between the disease and behaviour, lifestyle, home and external environmental factors is crucial. This paper reports the preliminary stages of an interdisciplinary research project involving dermatologists, epidemiologists and health geographers, and calls for investigation into associations between atopic eczema and possible environmental and lifestyle factors. These include behavioural factors, microenvironment factors and macroenvironments.     

Cohort study of effect of being overweight and change in weight on risk of coronary heart disease in old age

OBJECTIVE: To evaluate risk of late life coronary heart disease associated with being overweight in late middle or old age and to assess whether weight change modifies this risk. DESIGN: Longitudinal study of subjects in the epidemiological follow up study of the national health and nutrition examination survey I. SETTING: United States. SUBJECTS: 621 men and 960 women free of coronary heart disease in 1982-84 (mean age 77 years). MAIN OUTCOME MEASURE: Incidence of coronary heart disease. RESULTS: Body mass index of 27 or more in late middle age was associated with increased risk of coronary heart disease in late life (relative risk = 1.7 (95% confidence interval 1.3 to 2.1)) while body mass index of 27 or more in old age was not (1.1 (0.8 to 1.5)). This difference in risk was due largely to weight loss between middle and old age. Exclusion of those with weight loss of 10% or more increased risk associated with heavier weight in old age (1.4 (1.0 to 1.9)). Thinner older people who lost weight and heavier people who had gained weight showed increased risk of coronary heart disease compared with thinner people with stable weight. CONCLUSIONS: Heavier weight in late middle age was a risk factor for coronary heart disease in late life. Heavier weight in old age was associated with an increased risk once those with substantial weight loss were excluded. The contribution of weight to risk of coronary heart disease in older people may be underestimated if weight history is neglected.     

Acute opioid dependence in the cardiovascular system of the spinal rat

A cluster of infections caused by Enterobacter cloacae was observed among preterm neonates in a neonatal intensive care unit (NICU) of a pediatric hospital in Osnabrück, Germany. The presence of similar antimicrobial susceptibility patterns among the bacterial isolates prompted an investigation to determine whether a limited spread of a single strain existed. All 12 E. cloacae isolates from the NICU and 50 nonrelated strains were fingerprinted by small-fragment restriction endonuclease analysis (SF-REA) of EcoRI DNA digests. Selected isolates were further characterized by pulsed-field gel electrophoresis (PFGE) of NotI- or XbaI-generated genomic restriction fragments. Epidemiologically unrelated strains were clearly discriminated by both methods. Results achieved by SF-REA and PFGE revealed that of the 12 isolates from the NICU, 11 belonged to the same genotypic cluster. Since all reagents and equipment for both techniques are commercially available, DNA fingerprinting by SF-REA or PFGE is proposed as a useful tool in the microbiology laboratory for investigating the epidemiological relatedness of E. cloacae strains of clinical and environmental origin.     

Functional evidence of inhibitory reno-renal reflexes in spontaneously hypertensive rats

OBJECTIVES: Radium induces bone sarcomas at high doses, but there is controversy about risk at low doses. A previous study in Ontario found an association between the presence of radium in birthplace water supplies and an increased risk of death from bone cancer in young people. An investigation was performed to test the findings of the previous study with an independent group of subjects for whom complete information on radium exposure would be obtained. METHODS: A population based case-control study (238 cases; 432 controls) was conducted with incident cases of bone sarcoma identified from the Ontario cancer registry. Residential histories were collected by questionnaire and water samples were obtained and analysed for radium content. RESULTS: There was an association between risk of osteosarcoma and birthplace exposures (odds ratios (ORs) and 90% confidence intervals (90% CIs) 1.77 (1.03-3.00) but not with lifetime measures of exposure. When lifetime exposure was dichotomised, the OR was 1.31 (0.76-2.24) for osteosarcoma. There was no trend with increasing exposure. Bootstrap resampling was used to simulate lifetime doses in a pooled analysis of 1293 subjects from the two Ontario studies. The ORs were 1.38 (1.08-1.73) for all sarcomas, and 1.44 (1.01-1.87) for osteosarcoma. Geometric mean doses in bone were about 26 mRad. CONCLUSIONS: An association was found between the presence of radium in birthplace water supplies and increased risk of bone sarcoma in two studies. Increased risk was present for lifetime measures of exposure, but the association was not significant, and there was no dose-response trend. Our findings are compatible with the absence of risk at low doses, but they might also reflect inadequate statistical power to measure a true risk at environmental exposure levels. If the increased risk at environmental doses is causal, risk of bone sarcoma is effectively linearly related to dose over five orders of magnitude.