Disease Risk Factor Study Research Articles

Atrial Fibrillation and Dementia: Epidemiological Insights on an Undervalued Association

Background and objectives: Atrial fibrillation (AF) and dementia are growing causes of morbidity and mortality, representing relevant medical and socioeconomic burdens. In this study, based on data from the Global Burden of Disease Injuries and Risk Factors Study (GBD) 2019, we focused on AF and dementia distribution and investigated the potential correlation between the two epidemiological trends. Materials and Methods: Crude and age-standardized incidence, prevalence, mortality rate, and disability-adjusted life years (DALYs) lost, derived from GBD 2019, were reported for AF and dementia. Global features were also stratified by high and low sociodemographic-index (SDI) countries. Granger test analysis was performed to investigate the correlation between AF and dementia incidence time trends. Results: From 1990 to 2019 crude worldwide incidence and prevalence showed a dramatic increase for both conditions (from 43.24 to 61.01 and from 528.72 to 771.51 per 100,000 individuals for AF, respectively; from 54.60 to 93.52 and from 369.88 to 667.2 per 100,000 individuals for dementia, respectively). In the same timeframe, crude mortality rate doubled for AF and dementia (from 2.19 to 4.08, and from 10.49 to 20.98 per 100,000 individuals, respectively). Age-standardized estimate showed a substantial stability over the years, highlighting the key role of the progressively aging population. Crude estimates of all of the investigated metrics are greater in high SDI countries for both conditions. This association was still valid for age-standardized metrics, albeit by a reduced magnitude, suggesting the presence of higher risk factor burden in these countries. Finally, according to Granger test, we found a significant association between the historical trends of AF and dementia incidence (p = 0.004). Conclusions: AF and dementia burden progressively increased in the last three decades. Given the potential association between these two conditions, further clinical data assessing this relationship is needed.

Effects of data preprocessing on results of the epidemiological analysis of coronary heart disease and behaviour-related risk factors

Background We carried out this study to demonstrate the effects of outcome sensitivity, participant exclusions, and covariate manipulations on results of the epidemiological analysis of coronary heart disease (CHD) and its behaviour-related risk factors. Material and methods Our study population consisted of 1592 54-year-old men, who participated in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. We used the Cox proportional-hazards model to predict the hazard of CHD and applied different sets of outcomes concerning outcome sensitivity and data preprocessing procedures regarding participant exclusions and covariate manipulations. Results The mean follow-up time was 23 years, and 730 men received the CHD diagnosis. Cox regressions based on data with no participant exclusions most often discovered statistically significant associations. Loose inclusion criteria for study participants with any CVD during the follow-up and strict exclusion criteria for participants with no CVD were best in discovering the associations between risk factors and CHD. Outcome sensitivity affected the associations, whereas the covariate type, continuous or categorical, did not. Conclusions This study suggests that excluding study participants who are not disease-free at baseline is probably unnecessary for epidemiological analyses. Epidemiological research reports should present results based on no data exclusions together with results based on reasoned exclusions.

The quantitative analysis of neurodegenerative disease: classification, noda, constellations, and multivariate geometry

A variety of methods are available for the quantitative description and analysis of neurodegenerative disease. If neurodegenerative disease exists as a series of distinct disorders, then classificatory methods such as hierarchical cluster analysis (HCA) and decision tree analysis (DTA) can be used to classify cases into groups more objectively. If neurodegenerative disease consists of overlapping phenotypes, then the Braun-Blanquet 'nodal' system and 'constellation diagrams' implicitly recognise intermediate cases and reveal their relationships to the main groupings. By contrast, if cases are more continuously distributed without easily distinguishable disease entities, then methods based on spatial geometry, such as a triangular system or principal components analysis (PCA), may be more appropriate as they display cases spatially according to their similarities and differences. This review compares the different methods and concludes that as a result of the heterogeneity and overlap commonly present plus the multiplicity of possible descriptive variables, methods such as PCA are likely to be particularly useful in the quantitative analysis of neurodegenerative disease. A more general application of such methods, however, has implications for studies of disease risk factors and pathogenesis and in clinical trials.

Incorporation of Biological Knowledge Into the Study of Gene-Environment Interactions.

A growing knowledge base of genetic and environmental information has greatly enabled the study of disease risk factors. However, the computational complexity and statistical burden of testing all variants by all environments has required novel study designs and hypothesis-driven approaches. We discuss how incorporating biological knowledge from model organisms, functional genomics, and integrative approaches can empower the discovery of novel gene-environment interactions and discuss specific methodological considerations with each approach. We consider specific examples where the application of these approaches has uncovered effects of gene-environment interactions relevant to drug response and immunity, and we highlight how such improvements enable a greater understanding of the pathogenesis of disease and the realization of precision medicine.

Abstract P194: Gene-Environment Interactions and Blood Lipid levels: a Twin Study

Genetic variation may affect blood lipid levels by directly determining levels (‘level genes’) and/or by influencing the response to environmental factors (‘variability genes’), i.e. gene-environment interaction. Previous dietary studies assessing variability gene effects have produced inconsistent results, perhaps due to a lack of statistical power, different dietary protocols, and/or differences in the age, sex, habitual diet, baseline lipid values and other genes of the participants. Monozygotic (MZ) twins can enhance our ability to identify variability genes because they are genetically identical and also share the same age, sex and aspects of their early environment. Therefore, all intrapair differences in blood lipid levels are due to environmental factors such as diet and lifestyle, and variation between genotypes in intrapair differences will indicate the existence of variability genes. We investigated the hypothesis that polymorphisms within the genes for apoB, apoE and lipoprotein lipase influence the blood lipid response to environmental factors. The subjects studied were 64 MZ male and female twin pairs aged 18-75 years who had been recruited for a study of coronary heart disease risk factors in twins. Blood samples already taken for analysis of fasting lipid levels were used for DNA extraction. Genotypes were determined for the polymorphisms apoB signal peptide insertion/deletion (I/D), apoB Xba I, apoE, and lipoprotein lipase Pvu II, Hind III and S447X. Mean intrapair differences in lipid levels adjusted for mean twin pair lipid level were calculated for each genotype group. In MZ twins, carriers of the apoB signal peptide D allele had smaller intrapair differences in total cholesterol (p=0.044) but larger intrapair differences in apoAI (p=0.035) than I/I twins, and apoE ε4 carriers had smaller intrapair differences in HDL-cholesterol than E3/3 and E3/2 twins (p=0.024). MZ twins with the Pvu II P-P- genotype had significantly greater intrapair differences in apoB than P-P+ or P+P+ twins. The Xba I, Hind III and S447X polymorphisms did not influence intrapair differences in lipid levels. In conclusion, the apoB signal peptide I/D, apoE and lipoprotein lipase Pvu II polymorphisms may act as variability genes and influence the susceptibility of blood lipid levels to dietary and pharmacological interventions for dyslipidaemia. The approach of using MZ twins to identify variability genes can be applied to other phenotypes, prior to determining the environmental factors that interact with the genes to influence the phenotype.

Serum polyunsaturated fatty acids are not associated with the risk of severe depression in middle-aged Finnish men: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

The aim of this study is to investigate whether serum n-3 polyunsaturated fatty acids (PUFAs) or n-6 to n-3 ratio is associated with risk of severe depression in middle-aged Finnish men. The association between the serum concentrations of fatty acids and depression was investigated in 2077 men aged 42-60 years at baseline in a prospective follow-up setting. The population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study cohort was recruited between 1984 and 1989 and followed until the end of 2007. The baseline levels of serum total n-3 PUFAs, n-6 PUFAs and individual fatty acids were determined. Data on hospital treatments due to major depressive disorder were derived from the national hospital discharge register. During the average follow-up time of 18years, 46 men received a discharge diagnosis of depression. When the Cox proportional hazards model was adjusted for age, examination year, baseline socioeconomic status, alcohol consumption, smoking, maximal oxygen uptake and body mass index, there was no association between serum total n-3 PUFAs and the risk of depression [relative risk (RR) in the highest compared to the lowest tertile 0.71, 95% confidence interval (CI): 0.38; 1.43]. Serum concentrations of n-6 PUFAs, n6/n3 PUFA ratio, or individual fatty acids were not associated with the risk of severe depression, either. We did not find evidence that serum n-3 PUFA concentration or n-6/n-3 ratio would be associated with risk of severe depression in middle-aged Finnish men.

Blood pressure in adult rural INDEPTH population in Asia

Introduction: High blood pressure (BP) is a well-known major risk factor for cardiovascular diseases and is a leading contributor to cardiovascular mortality and morbidity worldwide. Reliable population-based BP data from low–middle income countries are sparse.Objective: This paper reports BP distributions among adults in nine rural populations in five Asian countries and examines the association between high BP and associated risk factors, including gender, age, education, and body mass index.Methods: A multi-site cross-sectional study of the major non-communicable disease risk factors (tobacco and alcohol use, fruit and vegetable intake, physical activity patterns) was conducted in 2005 in nine Health and Demographic Surveillance System (HDSS) sites in five Asian countries, all part of the INDEPTH Network. In addition to the self-report questions on risk factors, height and weight, and BP were measured during household visits using standard protocols of the WHO STEPwise approach to Surveillance.Results: In all the study sites (except among men and women in WATCH and among women in Chililab), the mean levels of systolic BP were greater than the optimal threshold (115 mmHg). A considerable proportion of the study populations – especially those in the HDSS in India, Indonesia, and Thailand – had high BP (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or on treatment with BP medications). A more conservative definition of high BP (systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg) substantially reduced the prevalence rate. The marked differences in the proportion of the populations on high BP medication (range between 0.6 and 10.8%) raised problems in comparing the prevalence of high BP across sites when using the commonly used definition of high BP as in this study. In the four HDSS in Bangladesh, women had a higher prevalence of high BP than men; the reverse was true in the other sites (Chililab, Filabavi in Vietnam; Kanchanaburi, Thailand; and Vadu, India) where men experienced higher prevalence than women. Overweight and obesity were significantly associated with high BP, with odds ratio ranging from two in Chililab to five in Filabavi (both in Vietnam HDSS).Conclusion: The patterns of BP in these nine cross-sectional surveys were complex, reflecting the fact that the Asian countries are at different stages of the epidemiological transition. Actions to prevent the rise of BP levels are urgently required. An emphasis should be placed on cost-effective interventions to reduce salt consumption in the population as an immediate priority.

Alcohol consumption and risk of colorectal cancer: the Findrink study

We investigated the association between alcohol consumption and colorectal cancer because previous studies have yielded conflicting results. As part of the Findrink study, data from the Kuopio Ischaemic Heart Disease (KIHD) Risk Factor Study were analysed. The KIHD study is a cohort of 2,682 men from Eastern Finland with no history of cancer at baseline. The men were grouped into five groups according to their weekly alcohol intake in grams. Association between alcohol and colorectal cancer was examined using Cox proportional hazard models. There were 59 cases of colorectal cancer during an average follow up of 16.7 years. Men within the highest quintile of alcohol consumption had a median weekly alcohol intake of 198.8 g. Age and examination year adjusted risk ratio of colorectal cancer among men within the highest quintile of alcohol consumption was 4.4 (95% CI: 1.6-11.9, P-value = 0.004). After adjusting for potential confounders, such as vegetable consumption, fibre intake, smoking, family history of cancer, socio-economic status, leisure time physical activity, men with the highest amount of alcohol consumption still had a 3.5-fold (95% CI: 1.2-9.9, P-value = 0.021) increased risk of colorectal cancer. Exclusion of men diagnosed with colorectal cancer during the first 2 years of follow up from the analyses did not alter the risk increase. In conclusion, this study gives further evidence of a positive association between alcohol consumption and the risk of colorectal cancer.

Beyond randomized controlled trials: A critical comparison of trials with nonrandomized studies

Observational analogs of randomized clinical trials (RCTs) are well accepted in the study of disease risk factors, diagnosis, and prognosis. There is controversy about observational studies when the focus is on the intended benefit due to lack of blinding and poor control for unmeasured confounding. Well-designed randomized clinical trials are costly both in time and money. Therefore, existing databases are used increasingly and are often the only feasible source with which to examine delayed health effects. We reviewed the reasons for possible discrepancies between RCTs and observational studies. There can be different patient populations, differences in therapeutic regimen, control of confounding, follow-up, measuring outcome, and differences arising from the intention-to-treat analysis. Observational studies cannot replace trials, nor do trials make observational studies unnecessary. Both designs are susceptible to particular bias, so neither provides perfect information.

Evaluation of Lipid-Lowering Therapy and Cholesterol Goal Attainment in Finland

European and US study findings show that patients in primary care and specialty care are not adequately treated for cholesterol reduction. To evaluate lipid-lowering treatment in Finland, estimate the proportions of subjects who are achieving cholesterol goals, and assess the influence of determinants on goal attainment. Subgroup analysis of the FINRISK study, a national study of cardiovascular disease risk factors in Finland. Study participants, the subgroup of patients on lipid-lowering therapy from FINRISK, completed a postal self-administered questionnaire on health/health behavioral factors. Serum total cholesterol (TC) and other clinical variables were measured using a standardized protocol. Ten-year coronary risk was computed using Framingham risk equations. The influence of certain factors on goal attainment was determined by logistic regression analysis. The main outcome measure was the proportion of subjects who were receiving lipid-lowering therapy and achieved a TC goal of <5 mmol/L (<194 mg/dL). Among 9581 respondents, 622 subjects were on lipid-lowering therapy. Of these, 68 subjects were excluded because of missing data on TC and/or the type/dose of therapy. Among the 554 subjects included, 210 (38%) were secondary-prevention patients and 51% had 10-year coronary risk >/=20%. Approximately two-thirds of subjects were prescribed simvastatin (42%) or atorvastatin (26%), and about half (51%) were prescribed low-equipotency HMG-CoA reductase inhibitors (statins). There was no difference in equipotent doses of statins prescribed for primary and secondary prevention. About half (54%) of subjects did not attain their cholesterol goal (TC <5.0 mmol/L [194 mg/dL]). Subjects with coronary heart disease (odds ratio [OR] 3.00; 95% CI 2.07, 4.35) and patients prescribed medium-to-high equipotent statins (OR 1.93; 95% CI 1.35, 2.76) were more likely to achieve cholesterol goals, whereas postmenopausal women (OR 0.61; 95% CI 0.42, 0.88) were less likely than men to achieve cholesterol goals. Most (92%) patients receiving lipid-lowering therapy in a Finnish population were managed on statin monotherapy and approximately half of the patients did not achieve their recommended cholesterol goals. More effective and safe therapies are needed to enhance cholesterol goal attainment. These treatments might include regimens that act on two or more pharmacologic pathways.

Insulin Resistance, Obesity, and Incident Heart Failure

Obesity and heart failure (HF) are both growing epidemics. To explore the relation between them — specifically, the potential role of insulin resistance — researchers followed 1187 Swedish men (age ≥70) enrolled in a prospective, community-based, observational study of metabolic risk factors for cardiovascular disease. …

A descriptive study of physical activity and cardiovascular disease risk factors in a defined population of older adolescent girls

A descriptive study of physical activity and cardiovascular disease risk factors in a defined population of older adolescent girls

Aggregate data studies of disease risk factors

Statistical methods are proposed for estimating relative rate parameters, based on estimated disease rates and covariate data from random samples of individuals from each of several cohorts. A random effects model is used to derive mean and variance models for estimated disease rates. Estimating equations for relative rate parameters are then developed by replacing cohort covariate averages by corresponding sample averages. The asymptotic distribution of regression parameter estimates is derived, and the asymptotic bias is shown to be small, even if covariates are contaminated by classical random measurement errors, provided the covariate sample size in each cohort is not small. Simulation studies, motivated by international data on diet and breast cancer, provide insights into the properties of the proposed estimators.

Aggregate Data Studies of Disease Risk Factors

Statistical methods are proposed for estimating relative rate parameters, based on estimated disease rates and covariate data from random samples of individuals from each of several cohorts. A random effects model is used to derive mean and variance models for estimated disease rates. Estimating equations for relative rate parameters are then developed by replacing cohort covariate averages by corresponding sample averages. The asymptotic distribution of regression parameter estimates is derived, and the asymptotic bias is shown to be small, even if covariates are contaminated by classical random measurement errors, provided the covariate sample size in each cohort is not small. Simulation studies, motivated by international data on diet and breast cancer, provide insights into the properties of the proposed estimators.

Coronary heart disease risk factors in women

Coronary heart disease is the leading cause of death among women. Reported risk factors for women are smoking, use of oral contraceptives, diabetes, elevated blood pressure, elevated blood lipids, low socio-economic status, low educational attainment, Type A behaviour and chronic troubling emotions. Via an on-line literature search (Medline and Psychlit) all case-control and prospective studies of coronary heart disease risk factors in women have been collected from 1978 to 1993. Smoking remains the most prominent risk factor for myocardial infarction in young women, the risk increasing significantly with the amount of cigarettes smoked. Use of modern low-dose oral contraceptives in healthy, non-smoking women does not increase the risk. Oestrogen replacement therapy seems to protect against coronary heart disease, although the reduction in risk may have been over-estimated. Elevated cholesterol and elevated blood pressure are major risk factors, and diabetes seems to have a stronger impact on risk in women than in men. Low socio-economic class is a stronger risk factor for women than for men and the double loads of career and family seem to increase risk for women.

Characteristics of participants and nonparticipants in the NHLBI Twin Study.

The NHLBI Twin Study is a longitudinal study of cardiovascular disease risk factors in 514 pairs of white, middle aged, male, veteran twins. The initial examination took place between 1969-1973. Ten years later, 81% of the living cohort returned for a second examination. Data collected up to 30 years prior to recruitment for the initial examination were used to characterize participants and nonparticipants; data from the initial examination were used to characterize returnees and nonreturnees to the second examination. Participants had significantly lower diastolic blood pressure and higher socioeconomic status than nonparticipants as measured thirty years earlier. Between the first and second examinations, the mortality of participants was less than 50% of the mortality of nonparticipants. Returnees to the second examination had a better health profile at the initial examination than nonreturnees, with significantly lower levels of cigarette smoking, glucose intolerance, hypertension, and diabetes and higher levels of pulmonary function. However, returnees were more obese than nonreturnees. Thus, this study of cardiovascular disease risk factors in twins appears to be affected by response bias in a way similar to studies of individuals. Additional analyses of biases that may affect the genetic component of the study indicated that factors related to classical twin analyses were relatively unaffected by selection.

Relative risk regression analysis of epidemiologic data.

Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation procedures with moderate numbers of disease events.

Risk Factors for Coronary Heart Disease in Hispanic Populations: A Review

Epidemiological studies of coronary heart disease (CHD) risk factors among Hispanics were examined. Hispanics as compared with Anglo Americans and blacks appear to have somewhat lower mortality rates of CHD. This suggests that Hispanics may have lifestyle patterns which reduce CHD risk in the areas of stress, diet, exercise, hypertension, and smoking. However, independent studies report that their samples of Mexican American subjects, but not Puerto Rican subjects, had higher blood lipid levels, greater rates of being overweight, and participate in less aerobic exercises as compared with same sex and aged Anglo American cohorts. By contrast, adult Mexican Americans and Puerto Ricans tend to smoke less than do Anglo American cohorts, although some evidence suggests that Hispanic adolescents may smoke more than do their Anglo American peers. The CHD risk status of Hispanics is summarized and recommendations for future research and health promotion programs are made.

The National Heart Institute Twin Study.

During the past two decades prospective epidemiologic studies have established the association between several risk factors and coronary heart disease. Elevations of serum cholesterol and blood pressure, obesity, lack of physical activity and cigarette smoking are among the factors which have been related to an increased risk of heart disease. We are now entering a period in which vigorous efforts will be made to modify these factors in order to prevent the occurrence of heart disease. An important part of this effort will be to determine to what extent these factors are genetically controlled and to what extent they can be modified by manipulation of the individual environment. Recognizing this need, the Field Epidemiological Research Section, National Heart Institute, NIH, has recently embarked on a study of cardiovascular disease risk factors in a large sample of adult male twins. The purpose of the present report is to describe the protocol and methods to be used and the importance of this study to current research in cardiovascular disease.