Associations between cardiovascular disease and its risk factors with hearing loss-A cross-sectional analysis.

OBJECTIVES: To investigate the relationship between hearing loss and cardiovascular disease risk factors. DESIGN: Cross-sectional study. METHODS: Participants were recruited between May 2010 and December 2015 and answered a health and risk factor questionnaire. Physical and biochemical assessments were performed. SETTING: A community-based population. PARTICIPANTS: A total of 5107 participants born within the years 1946-1964 enrolled in the Busselton Healthy Ageing Study. MAIN OUTCOME MEASURES: Hearing was assessed behaviourally through the best ear pure-tone average (500, 1000, 2000, 4000 Hz), low-frequency average (250, 500, 1000 Hz) and high-frequency average (4000, 8000 Hz). Self-reported hearing loss, tinnitus and hyperacusis were assessed via questionnaire. Cardiovascular risk factors were assessed via a patient-completed questionnaire and objective measurements including blood pressure, body mass index, waist circumference, lipid profile and glycated haemoglobin. RESULTS: Of the participants, 54% were female, with the mean age of 58 years (range 45-69 years). Age, sex and family history of hearing loss were consistently strong determinants of hearing loss outcomes. After adjusting for these, obesity, current smoking, peripheral arterial disease and history of cardiovascular disease were significantly associated with pure-tone, low-frequency and high-frequency hearing loss. In addition, high blood pressure, triglyceride and glycated haemoglobin were significantly associated with low-frequency hearing loss. There was a graded association between hearing loss and Framingham Risk Score for cardiovascular risk (P<0.001). CONCLUSIONS: Established cardiovascular disease and individual and combined cardiovascular disease risk factors were found to be associated with hearing loss. Future research should prospectively investigate whether targeting cardiovascular disease can prevent hearing loss.

Gastro-oesophageal reflux and respiratory symptoms in Busselton adults: the effects of bodyweight and sleep apnoea.

BACKGROUND/AIM: Respiratory symptoms and gastro-oesophageal reflux disease (GORD) are common within the general population. Although a number of epidemiological studies have addressed their relationship, none has investigated the confounding effects of body mass index (BMI) and obstructive sleep apnoea (OSA), both of which are associated with reflux. METHODS: Men and women (2700) from the 2005-2007 cross-sectional Busselton health survey were included. Questionnaire data included demography, information on general health, asthma, cough, wheeze, dyspnoea and reflux symptoms (never, monthly or less often and weekly or more often). BMI, risk of OSA (Berlin questionnaire definition), spirometry and airway hyperresponsiveness (AHR) were recorded. The effects of BMI and OSA on the relationship between respiratory and reflux symptoms were examined using logistic regression models, expressed as adjusted odds ratios for risk of respiratory symptoms by reflux symptom category. RESULTS: Fifty per cent had reflux symptoms (5-10% weekly or more often). Reflux symptoms had strong positive, dose-related associations with cough/phlegm, breathlessness, chest tightness and wheeze in the last 12 months (P < 0.001), but were not related to diagnosed asthma or AHR. Twenty-three per cent were at high risk of OSA and 63% had a BMI of >25 (22% > 30). Increased weight or high risk of OSA did not affect the relationship between respiratory symptoms and reflux symptoms. CONCLUSION: The relationship between reflux and respiratory symptoms was independent of BMI, high risk of OSA or AHR. These findings suggest that reflux contributes directly to respiratory symptoms.

Changes in the prevalence of asthma in adults since 1966: the Busselton health study.

Asthma prevalence has increased worldwide; although less so in developed countries recently. This study assessed changes in the prevalence of asthma and related symptoms in the Busselton community since 1966. Cross-sectional respiratory health surveys of Busselton adults were conducted in 1966, 1969, 1972, 1975, 1981, 1990 and 2005-2007. Logistic regression models were used to estimate prevalence rates of asthma, respiratory symptoms, smoking, airway hyperresponsiveness (AHR) and atopy and to make comparisons in 2005-2007 and previous survey years. Asthma was defined as ever having doctor-diagnosed asthma (DDA). The prevalence of DDA was around 6% from 1966 to 1975, 8% in 1981 and rose to 19% in 2005-2007. From 1981 to 2005-2007, smoking prevalence declined and obesity and atopy increased but changes in these variables explained only a small part of the increase in DDA. Wheeze and cough/phlegm increased but AHR, breathlessness and doctor-diagnosed bronchitis remained relatively stable over the same period. These observations indicate that the increase in DDA is partly explained by increased symptoms and atopy. The lack of changes in AHR and doctor-diagnosed bronchitis suggests that factors such as diagnostic transfer and increased awareness of asthma have also contributed to the rise in prevalence of DDA.

Serum ferritin and cardiovascular disease: a 17-year follow-up study in Busselton, Western Australia.

The association between serum ferritin level and coronary heart disease (CHD) and stroke events was evaluated in a long-term Western Australia prospective study in 1981-1998. The cohort consisted of the 1612 men and women aged 40-89 years who participated in the 1981 Busselton Health Survey and who were free of cardiovascular disease at that time. Serum ferritin levels were obtained from serum samples stored frozen since 1981. The outcomes of interest were time to first CHD event (hospital admission or death) and time to first stroke event. Case-cohort sampling was used to reduce costs and preserve serum but still allow efficient analysis. Ferritin assays were performed for 217 CHD cases, 118 stroke cases, and a random sample of 450 of the total cohort. Proportional hazards regression models were used to obtain age-adjusted and multivariate-adjusted hazard ratios for ferritin level in relation to CHD and stroke. The hazard ratio for the highest tertile group compared with the lowest group was 0.96 (95% confidence interval: 0.60, 1.53) for CHD and 1.43 (95% confidence interval: 0.78, 2.64) for stroke. Little or no evidence was found that ferritin level was a risk factor for cardiovascular disease.

Familial aggregation and heritability of adult lung function: results from the Busselton Health Study.

Decreased spirometric indices are characteristic of asthma and other respiratory diseases. The aim of this study was to investigate the genetic and environmental components of variance of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured in adulthood in an Australian population-based sample of 468 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits with asthma and atopic rhinitis were also investigated. Serial cross-sectional studies were conducted in the town of Busselton in Western Australia between 1966 and 1981 and follow-up of previous attendees was undertaken in 1995. Data from each subject included in this study were from a single survey in adulthood (25-60 yrs of age) when the subject was as close to age 45 yrs as possible. Multivariate analysis suggested that FEV1 and FVC levels were associated with age, sex, height, tobacco smoke exposure, asthma and atopic rhinitis. After adjustment for relevant covariates, FEV1 levels had a narrow-sense heritability (h2N) of 38.9% (SE 9.1%). FVC levels had an h2N of 40.6% (SE 8.9%). Extended modelling demonstrated little overlap in the genetic determinants of asthma or atopic rhinitis and either FEV1 or FVC levels. The results of this study were consistent with the existence of important genetic determinants of adult lung function that are independent of asthma or other atopic disease, cigarette smoking, height, age or sex.

Associations between white blood cell count, lung function, respiratory illness and mortality: the Busselton Health Study.

An independent association between reduced levels of lung function and increased mortality from nonrespiratory causes has been observed in a number of studies. Since the total white blood cell count (WBC) has been related to both death from coronary heart disease and to levels of lung function, the relationship between these parameters was examined in subjects from the Busselton Health Surveys. Questionnaires regarding respiratory and cardiac illness and smoking habits were administered and total WBC, forced expiratory volume in one second (FEV1) and forced vital capacity measured in 2,105 males and 2,186 females at their initial attendance at a Busselton Health Survey in 1969, 1972 or 1975. Mortality follow-up to 1995 was completed. Multiple linear regression showed that smoking, increasing age, reduced FEV1 (% predicted) and a history of bronchitis were associated with increased WBC. Reduction of FEV1 (% pred) by 20%, a history of dyspnoea and an increase in WBC of 1,300 cells x mL(-1) were predictive of increased mortality from all causes or coronary heart disease by approximately 20, 100 and 10% respectively, independent of smoking. Removing WBC from the regression model did not significantly change the relationship between FEV1 and mortality. The study shows that the white blood cell count, forced expiratory volume in one second and dyspnoea are independently related to mortality in both males and females and that the effect of forced expiratory volume in one second on mortality is not explained by the white blood cell count.

Decline in lung function and mortality: the Busselton Health Study.

BACKGROUND: There is a direct association between level of lung function, measured by forced expiratory volume in 1 second (FEV1) and mortality rates. A low FEV may result from an increased decline in FEV1 with age, which may be an independent predictor of mortality. OBJECTIVE: To examine the association between decline in FEV1 and mortality in a cohort from a community health study. SETTING AND METHODS: From five cross sectional studies in Busselton between 1969 and 1981 a cohort of 751 men and 940 women was identified who had three assessments of lung function over a six year period and had other health related data collected. Each subject's average FEV1 and decline in FEV1 (litre/year) were calculated from these three measurements. Mortality follow up to December 1995 was obtained. Cause of death was taken as the certified cause of death from the death certificate using ICD9 categories. RESULTS: The average decline in FEV1 was 0.04 litre per year (SD = 0.07) for men and 0.03 litre per year (SD = 0.06) for women. Average FEV1 was significantly associated with all cause and cardiovascular disease mortality in both sexes. In women there was a significant association between decline in FEV1 and death from all causes, after adjusting for average FEV1, age, smoking, coronary heart disease, and cardiovascular disease risk factors; a 0.05 litre per year increase in the rate of decline of FEV1 increased the risk of death for all causes by 1.23 (95% confidence interval 1.06, 1.44). In men the effect of decline in FEV1 on death rate was less; for all men the hazard ratio for a 0.05 litre/year greater decline in FEV1 was 1.19 (0.99, 1.21). CONCLUSION: Decline in lung function, measured by FEV1 is a predictor of death, independent of average FEV1 and risk factors for cardiovascular disease.

Lung function, respiratory symptoms, and mortality: results from the Busselton Health Study.

PURPOSE: This study examines the association between lung function [percentage predicted FEV, (forced expiratory volume in 1 s)] and respiratory symptoms (asthma, bronchitis, wheeze, dyspnea) and mortality from all causes; coronary heart disease, stroke, cancer, and respiratory disease in a cohort of 2,100 men and 2,177 women in the Busselton Health Study followed for 20-26 years for mortality. METHODS: A total of 840 men and 637 women died during the follow-up period, and Cox proportional hazards regression was used to assess the relationships between risk factors and mortality. RESULTS: Lung function was significantly and independently predictive of mortality from all causes, coronary heart disease, cancer, and respiratory disease in both men and women, and of mortality from stroke in women. There was evidence that, among men, the association was stronger in current and former smokers as compared to those who never smoked. After adjustment for age, smoking, lung function, coronary heart disease, blood pressure, treatment for hypertension, total cholesterol, body mass index, and alcohol consumption, dyspnea was significantly related to total mortality in men and women and to respiratory disease mortality in men, and asthma was significantly related to respiratory disease mortality in women. CONCLUSIONS: Lung function is associated with mortality from many diseases independent of smoking and respiratory symptoms. Although most respiratory symptoms are associated with smoking and lung function, after controlling for smoking and lung function, only dyspnea is associated with mortality from nonrespiratory causes.

Effect of dichotomising a continuous variable on the assessment of familial aggregation: an empirical study using body mass index data from the Busselton Health Study.

BACKGROUND: Continuous measures are often dichotomised according to some meaningful threshold. When measures of association are the study focus, such as in familial aggregation studies, we may use an odds-ratio (OR), instead of a Pearson correlation coefficient, to measure correlation between outcomes. In this paper, we examine the effect of using different threshold values on the resulting OR estimates and their statistical efficiency. METHODS: We use an example based on obesity data, in the form of BMI measurements on family members, to guide a study of the OR based on four-fold probabilities which result when a pair of normally distributed outcomes is dichotomised at a certain value. This leads to a study of outcomes from simulated nuclear family data. As a possible alternative, we also assess the performance use of a simple tetrachoric correlation coefficient, the dichotomous analogue of Pearson's correlation coefficient. RESULTS: The studies indicate that dichotomisation at values close to the mean leads to results more comparable to the continuous equivalent. The results show that, in our setting, there is a positive relationship between threshold value and resulting OR, and between threshold value and resulting standard errors. The value of the tetrachoric correlation coefficient decreases, relative to Pearson's correlation coefficient, as threshold values deviate from the mean. DISCUSSION: Familial OR that result from dichotomisation are influenced by the choice of threshold value. We discuss implications of this and related issues on the interpretation of results.

Adjustment for regression dilution in epidemiological regression analyses.

PURPOSE: The term "regression dilution" describes the dilution/attenuation in a regression coefficient that occurs when a single measured value of a covariate is used instead of the usual or average value over a period of time. This paper reviews the current knowledge concerning a simple method of adjusting for regression dilution in single and multiple covariate situations and illustrates the adjustment procedure. METHODS: Formulation of the regression dilution problem as a measurement error problem allows existing measurement error theory to be applied to developing methods of adjustment for regression dilution. This theory leads to a precise method of adjustment for linear regression and approximate methods for logistic and Cox proportional hazards regression. The method involves obtaining the naive estimates of coefficients by assuming that covariates are not measured with error, and then adjusting these coefficients using reliability estimates for the covariates. Methods for estimating the reliability of covariates from the reliability and main study data and a method for the calculation of standard errors and confidence intervals for adjusted coefficients are described. RESULTS: An illustration involving logistic regression analysis of risk factors for death from cardiovascular disease based on cohort and reliability data from the Busselton Health Study shows that the different methods for estimating the adjustment factors give very similar adjusted estimates of coefficients, that univariate adjustment procedures may lead to inappropriate adjustments in multiple covariate situations, whether or not other covariates have intra-individual variation, and when the reliability study is moderate to large, the precision of the estimates of reliability coefficients has little impact on the standard errors of adjusted regression coefficients. CONCLUSIONS: The simple method of adjusting regression coefficients for "regression dilution" that arises out of measurement error theory is applicable to many epidemiological settings and is easily implemented. The choice of method to estimate the reliability coefficient has little impact on the results. The practice of applying univariate adjustments in multiple covariate situations is not recommended.

Microalbuminuria in type 2 diabetes: an independent predictor of cardiovascular mortality.

BACKGROUND: Microalbuminuria has been shown to be associated with cardiovascular mortality in type 2 diabetic subjects. It is unclear to what extent this is due to the increased prevalence of other cardiac risk factors. AIMS: To examine the relationship of urine albumin excretion to cardiovascular mortality and to determine its status as an independent risk factor. METHODS: In a prospective longitudinal study from 1986-1993 we followed 666 type 2 diabetic subjects from a diabetes outpatient service. Cardiovascular risk factors including urine albumin concentration were measured at study entry. Cox proportional hazards regression was used to determine risk factors for mortality. The hazard ratios of microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary heart disease mortality were determined after accounting for other cardiac risk factors including blood pressure, glycated haemoglobin, total cholesterol, HDL cholesterol, triglycerides, urea, smoking, body mass index, patient age and disease duration. RESULTS: The prevalence of urine albumin of 30-300 mg/L at study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular disease). Mortality hazard ratios in subjects with urine albumin of 30-300 mg/L as compared to < 30 mg/L, adjusted for age, sex and other cardiovascular risk factors were 1.77 (95% CI 1.22-2.57, p = 0.002) for all causes, 2.34 (95% CI 1.38-3.99, p = 0.002) for cardiovascular and 1.78 (95% CI 0.97-3.26, p = 0.061) for coronary heart disease (CHD) mortality. Other factors significantly associated with cardiovascular mortality included diastolic blood pressure, HDL cholesterol and glycated haemoglobin. Total cholesterol and log triglyceride were significantly associated with CHD mortality. Disease duration, age at diagnosis, smoking and body mass index were not related to cardiovascular or CHD mortality. CONCLUSIONS: We confirm microalbuminuria as an independent predictor of mortality in type 2 diabetes despite its association with a number of conventional cardiovascular risk factors.

Familial correlations, cohabitation effects, and heritability for cardiovascular risk factors.

Familial correlations in cardiovascular risk factors were investigated with use of data from a community-based sample of 1319 nuclear families involving 4178 adult persons collected in the Busselton Population Health Surveys over the period 1966 to 1981. The risk factors considered were systolic blood pressure, diastolic blood pressure, body mass index, triceps fatfold, and cholesterol. All risk factors showed positive familial correlations, with correlations generally being lower for spouses than for parent-offspring pairs or for siblings. Spouse correlations showed little variation with age, suggesting that observed correlations are primarily due to assortative mating and not to cohabitation. The parent-offspring correlations tended to decline with age of (adult) offspring; this observation suggests that the effect of a shared household environment during childhood and adolescence diminishes over time when living apart during adulthood. The sibling correlations decreased with age for blood pressure and serum cholesterol and increased with age for body mass index and triceps fatfold. The estimated heritabilities were 27% for systolic and diastolic blood pressure, 37% for serum cholesterol, 52% for body mass index, and 23% for triceps fatfold. These results confirm that substantial familial aggregation of cardiovascular risk factors occurs and that much of this aggregation has a genetic basis, although assortative mating (in spouses) and environmental influences (in offspring and siblings) are also present. The nuclear family should be considered as a point of intervention in cardiovascular disease prevention programs.

Spouse correlations in cardiovascular risk factors and the effect of marriage duration.

Spouse correlations in cardiovascular risk factors were investigated using data on 2,836 spouse pairs collected in the Busselton Population Health Surveys over the period 1966-1981. The risk factors considered were systolic blood pressure, diastolic blood pressure, body mass index, triceps fatfold, cholesterol, and forced expiratory volume (1 second). Statistically significant positive correlations (p < 0.01) were found for all (age-adjusted) variables. There was a statistically significant decreasing trend in the correlations for systolic blood pressure with marriage duration (trend p < 0.01). Although no other variables showed statistically significant trends, the correlations for diastolic blood pressure (p = 0.29), body mass index (p = 0.14), and forced expiratory volume (p = 0.16) also decreased with marriage duration, and correlations for cholesterol (p = 0.61) and triceps fatfold (p = 0.99) increased with marriage duration. These results suggest that there is spousal concordance in cardiovascular risk factors. The lack of consistent increasing trends in the correlations with marriage duration suggests that assortative mating may be a more likely explanation than the sharing of a common environment.

Age and secular trends in risk factors for cardiovascular disease in Busselton.

Mortality rates from heart disease and stroke in Australia have been falling for more than 20 years. No completely satisfactory explanations for this trend exist. However, it is believed to be due, at least in part, to changes in the incidence of cardiovascular disease arising from changes in the prevalence and severity of risk factors for cardiovascular disease. The adult community of Busselton in Western Australia participated in cross-sectional health surveys every three years from 1966 to 1981. This paper describes secular trends from 1966 to 1981 and age trends from 25 to 80 years for cardiovascular risk factors in Busselton men and women. Downwards secular trends were observed for mean blood pressure and smoking for men and women, upwards trends were observed for body mass index in men, and mean cholesterol was approximately constant over this period. The age and secular trends were consistent with other Australian studies conducted in the 1980s and with overseas studies. An estimated 67 per cent of the decline in cardiovascular mortality rates among Busselton men and 22 per cent of the decline among Busselton women may be attributed to changes in the prevalence of risk factors for cardiovascular disease.