Heterozygous familial hypercholesterolaemia (FH) is a common autosomal dominant inherited metabolic disease with a prevalence of 1 in 500 in most Western countries. People with FH experience an increased risk for coronary artery disease (CAD) and excess mortality especially at a young age. Until recently the diagnosis of FH was based on clinical signs and symptoms alone. These included increased cholesterol concentrations, in particular of LDL-cholesterol, in combination with the presence of tendon xanthoma, corneal arcus, xanthelasmata and a history of early CAD. Frequently FH was diagnosed after a first cardiac event.@en

Aims: To estimate the cost-effectiveness of the current screening programme on Familial Hypercholesterolaemia (FH) in relatives of diagnosed FH-patients in The Netherlands. Methods and Results: Data from 2229 screened FH-relatives, including age, sex, risk factor status and screening outcome, were combined with the Framingham risk function and national disease-specific cost data to arrive at a model-based comparison of survival and costs, with and without the screening programme. Cost-effectiveness ratios were computed for various treatment strategies, with no screening as reference. Costs per life year gained varied between 25·5- and 32-thousand Euros, depending upon the precise treatment strategy after a positive screen. The costs for screening (tracing the FH-positive individuals) were much lower than the follow-up costs (treatment), of which 80% were costs for statins. Consequently, the costs per life year gained of alternative screening programmes are about the same. Conclusion: The cost-effectiveness ratio of FH screening is within the range requiring explicit political consideration in The Netherlands. As the costs of statin treatment are the single most important determinant of costs, policy decisions reduce to decisions on the acceptability of statin treatment for this risk group. Pending major changes in statin price, clear guidelines should be developed on how screen positive individuals should be treated, since not all of them have an elevated cholesterol level.@en

Objectives: To assess the screenees' views on, and the psychological impact of, a family-based genetic screening programme for familial hypercholesterolaemia (FH) and to evaluate non-participation. Methods: Self-administered questionnaires were filled out at the time of screening and after communication of the test result. Non-participants were interviewed by phone. Results: Of the people approached for screening, 2% did not participate. These 2% were not interested, had already been clinically diagnosed, or were afraid of insurance consequences. 677 screenees participated, of whom 215 (32%) tested FH positive. Less than 5% of the screenees were critical of the approach and the information provided. 20% of the screenees expressed feelings of social pressure. Effects on mood were minimal to absent, as were general 'quality of life' effects. Conclusions: Screening for FH is highly acceptable to screenees, although social pressure is prevalent. Only a small percentage of people being approached did not participate.

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Study objective - To explore whether the observed age related decline in the relative risk of death associated with low employment grade can be explained by the profiles of smoking, blood pressure and plasma cholesterol changing differently with age between the employment grades. Design - Prospective cohort study with 25 years of mortality follow up. Setting - Whitehall study. Participants - There were 16 984 men aged 40 to 69 years at baseline with complete information on smoking, blood pressure and plasma cholesterol. Main results - The relative risk of death associated with low employment grade decreased from 2.1 at 55-59 years of age to 1.3 at 85-89 years of age. Adjustment for smoking status and blood pressure, attenuated the age related decline of the relative risk by 18% and 3% respectively; adjustment for plasma cholesterol increased the decline by 3%. Taken together, these risk factors explain 20% of the observed age related decline. Conclusions - A small part of the observed age related decline in the relative risk of death associated with low employment grade can be explained by differential changes in the profiles of smoking, blood pressure and plasma cholesterol with age between the employment grades.@en

The quality of life (QoL) of survivors of a myocardial infarction (MI) remains lower than that of their peers long after the acute event. Previous research on this subject has indicated, however, that this difference might lessen somewhat over time for the dimension 'emotional functioning' (as measured by the sickness impact profile (SIP): A generic instrument for QoL). The present study explores this phenomenon further using two instruments that specifically measure emotional functioning i.e. the hospital anxiety and depression scale (HAD) and the heart patients psychological questionnaire (HPPQ). Ninety-nine participants of a large population-based cohort (the Rotterdam study), who had been admitted to the hospital because of an MI in the previous 6-60 months, and 101 reference subjects, without a history of infarction of heart or brain, from the same age and gender-groups, were interviewed twice (at 1- to 3-year time intervals). The results of the present study confirm earlier findings that the emotional functioning (in terms of 'anxiety', 'depression', 'well-being', 'feeling disabled', and 'displeasure') of MI survivors is impaired when compared to their unaffected peers. Moreover, they did not show any improvement in 'anxiety', 'depression', 'well-being' and 'displeasure' over time in the MI survivors. The results did, however, show that the difference between MI survivors and referents became less in time in the dimension 'feeling disabled'. This decrease was partly because MI survivors improved and partly because referents felt more disabled over time. One explanation for this might be that referents (51% aged 70 years and over) had difficulties in adapting emotionally to decreasing levels of physical functioning with increasing age, while the MI survivors tended to adjust to and accept the impairments they had contracted several years earlier.@en

Background. Prescott et al. found that the relative risks associated with smoking for respiratory and vascular deaths were higher for women who inhale than for inhaling men, and found no gender differences in relative risks of smoking-related cancers. The purpose of the present study was to assess whether these findings are reproducible, using data from the Renfrew and Paisley study. Methods. Age-standardized mortality rate differences and age-adjusted mortality rate ratios (using Cox's proportional hazard model) were calculated for male and female smokers by amount smoked compared with never smokers. These analyses were repeated after excluding non-inhalers. Results. The all-cause mortality rate ratio was higher for men than for women in all categories of amount smoked, although this difference was only statistically significant in the light smokers (1.83 [95% CI : 1.61-2.07] for men and 1.41 [95% CI : 1.28-1.56] for women, P = 0.001). The cause-specific mortality rate ratios tended to be higher for men than for women, and this difference was most substantial for neoplasms (2.57 [95% CI : 2.01-3.29] for male light smokers and 1.35 [95% CI : 1.14-1.61] for female light smokers, P < 0.001) and, in particular, for lung cancer (11.10 [95% CI : 5.89-20.92] for male light smokers and 4.73 [95% CI : 2.99-7.50] for female light smokers, P = 0.03). Furthermore, looking at the rate differences the effects of smoking were uniformly greater in men than in women. These results were virtually unchanged after excluding non-inhalers. Conclusion. We found similar results to Prescott et al. when all smokers were considered, but could not reproduce their findings when non-inhalers were excluded. Given the fact that we showed greater rate differences in men than in women, we think that it is too early to conclude that women may be more sensitive than men to some of the deleterious effects of smoking.@en

The present study aimed to compare survival to age 75 between men and women, by social circumstances and smoking behaviour. A 20 year follow up was carried out of a large representative cohort of Scottish men and women in the Renfrew and Paisley study, and was combined with Scottish mortality statistics. 6831 men and 7993 women aged 45-64 y at time of examination (between 1972 and 1976) were considered. Combining the estimates from the Renfrew and Paisley study with those from Scottish mortality statistics for men and women younger than 45 y of age, it was calculated that 28% of the male smokers and 44% of the male never smokers in disadvantaged social circumstances will have survived to age 75 y, compared with 46% and 56% of the female smokers and never smokers respectively. In more privileged social circumstances, 41% of the male smokers and 62% of the male never smokers will have survived to age 75 y, compared with 56% and 70% of the female smokers and never smokers respectively. The difference between male smokers in low social classes and female never smokers in high social classes is 42% in absolute terms (28% vs 70%), which gives an indication of the combined influence of gender, social circumstances and smoking on survival. These results show that gender, social circumstances and smoking are important determinants of mortality which have led to substantial differences in survival. The influence of additional factors related to mortality could usefully be compared to these to put their effects into perspective.@en

Objective. To estimate the proportion of patients with familial hypercholesterolaemia (FH) who were identified with hypercholesterolaemia in general practice prior to screening by means of pedigree research and DNA analysis by the National Foundation for the Identification of Familial Hipercholesterolemia (StOEH). Design. Retrospective. Method. General practice files of FH patients, diagnosed through genetic screening by the StOEH in 1992-1997 whose general practitioner's (GP's) practice in Amsterdam, Haarlem or Alkmaar, were studied for cholesterol and FH related information documented in the period prior to the screening. Results. Out of the 121 persons selected 80 agreed to the study; one GP refused to co-operate. There was no difference between respondents and non respondents with regard to age, sex or domicile of the GP. In 48 of 79 (61%) general practice files studied, cholesterol measurements were reported prior to screening; 39 patients (49%) had hypercholesterolaemia and 29 (37%) were being treated with cholesterol lowering drugs. Mean age of the FH patients who had no record of their cholesterol levels was 25.1 years (SD: 17.0) at the time of screening, 22 years younger than the mean age of FH patients who did have cholesterol levels on record prior to screening (47.1 (SD: 18.4); p < 0.0001). Conclusion. Of the FH patients identified through family based genetic screening especially the younger FH patients are newly brought to the attention of their GP.@en

Objective - To examine whether eliminating smoking will lead to a reduction in the number of years lived with disability (that is, absolute compression of morbidity). Design - Multistate life table calculations based on the longitudinal GLOBE study (the Netherlands) combined with the Longitudinal Study of Aging (LSOA, United States of America). Setting - The Netherlands. Subjects - Dutch nationals aged 30-74 years living in the city of Eindhoven and surrounding municipalities (GLOBE) and United States citizens age 70 and over (LSOA). Main outcome measures - Life expectancy with and without disability and total life expectancy at ages 30 and 70. Results - A non-smoking population on balance spends fewer years with disability than a mixed smoking-non-smoking population. Although non-smokers have lower mortality risks and thus are exposed to disability over a longer period of time, their lower incidence of disability and higher recovery from disability yield a net reduction of the length of time spent with disability (at age 30: -0.9 years in men and -1.1 years in women) and increases the length of time lived without disability (2.5 and 1.9 years, for men and women, respectively). These outcomes indicate that elimination of smoking will extend life and the period of disability free life, and will compress disability into a shorter period. Conclusions - Eliminating smoking will not only extend life and result in an increase in the number of years lived without disability, but will also compress disability into a shorter period. This implies that the commonly found trade off between longer life and a longer period with disability does not apply. Interventions to discourage smoking should receive high priority.@en

Blaxter has hypothesized that harmful behavioral habits like smoking have a greater impact on health in the non-manual than in the manual social classes, possibly because other adverse exposures have a more important role in the manual social classes. However, the outcome measure used was a composite measure of physiological indices of morbidity and the relevance of this to other health problems is uncertain. We have therefore investigated the effect of smoking on mortality, to test whether the risk of death associated with smoking differs between manual and non-manual social classes. Data on 6831 men and 7993 women, aged 45-64 when screened in the Renfrew and Paisley study, a large prospective observational study in the West of Scotland, have been analyzed. All cause mortality rate ratios for smokers compared with never smokers have been calculated within manual and non- manual social classes. Although the age adjusted rate ratios are slightly higher among the non-manual men and women (2.19 [1:83.-2.61] versus 1.92 [1.71-2.17] for non-manual and manual men respectively, and 1.75 [1.54-1.99] versus 1.65 [1.50-1.82] for non-manual and manual women), this difference between social classes is not statistically significant (p-values for test of difference 0,26 and 0.47 for men and women respectively). When additionally adjusted for other risk factors cardiorespiratory symptoms and deprivation, this picture remained the same (p-values for test of difference are 0.41 and 0.50 for men and women respectively). Similar results were found when the cohort was divided by deprivation categories rather than social classes or when smoking related mortality rather than mortality from all causes was used as the outcome measure. We therefore conclude that the health impact of smoking is similar in each socioeconomic group. The relative health improvement consequent on smoking cessation is thus similar in different socio-economic groups.@en

Study objective - To assess the size of mortality differentials in men by social class in Scotland as compared with England and Wales, and to analyse the time trends in these differentials. Subjects - Men from England and Wales and Scotland around each census from 1951 to 1981. Methods - Poisson regression analysis was used to calculate relative indices of inequality for disease specific and all cause mortality as a measure of mortality differentials between social classes. This measure is not dependent on the size of the social class groups, so it can be used to compare the magnitude of differentials over time periods during which the relative sizes of social class groups change. Main results - While overall death rates were higher in Scotland than in England and Wales around the 1951, 1961, and 1971 censuses the relative indices of inequality indicated smaller mortality differences between social classes in Scotland. Inequality, as indexed by the relative index of inequality, increased over time in both Scotland and England and Wales, but to a greater degree in Scotland, resulting in greater social class mortality differentials for Scotland in 1981 (the relative index of inequality increased from 1.40 to 2.43 for England and Wales, and from 1.22 to 2.57 for Scotland between 1951 and 1981). This greater increase in the magnitude of inequalities in all cause mortality in Scotland seemed to result from increasing social class differentials in cardiovascular disease, accidents and external causes, and 'all other causes of death'. Examining the trends in overall death rates, it seems that the greater increase in social class differences in Scotland occurred because of the greater decrease in death rates among the privileged social groups, in combination with a smaller decrease (or a greater increase) in the death rates in the lower social class groups. Conclusions - This study has shown that trends in mortality and in inequalities in mortality differ within Great Britain. Although death rates were higher in Scotland than in England and Wales, smaller mortality differentials by social class were found in Scotland over the period 1951 to 1971. By 1981, however, social class mortality differentials were greater in Scotland than in England and Wales. The greater increase in the social class differentials over time in Scotland, may have contributed to the worsening overall mortality profile in Scotland as compared with England and Wales that occurred between 1971 and 1981.

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Objectives. This study examined the variation in reported relative risks of coronary heart disease and stroke associated with hypertension and determined reasons for the interstudy variation. Methods. Studies published since 1972 were examined that reported the absolute number of events and person-years for men by age and hypertensive status. The data were pooled in Poisson regression models with the coronary heart disease or stroke rate as the dependent variable. Independent variables were hypertensive status, age at entry, age of study, duration of follow-up, diastolic blood pressure cut- off point, and interactions of all these variables with hypertensive status. Results. The reported relative risks associated with hypertension ranged from 1.45 to 2.77 for coronary heart disease and from 1.86 to 5.78 for stroke. Smaller relative risks were found in more recent studies, in studies using a lower cut-off point to define hypertension. Conclusions: Part of the interstudy variation in relative risks associated with hypertension can be attributed to differences in duration of follow-up, blood pressure cutoff point, and time at which blood pressure was measured, suggesting declining relative risks over time.@en

Little is known about the clustering of risk factors at a nation-wide level. As a result the prevalence of combinations of risk factors in models like PREVENT, designed to calculate the health benefits of a change in risk factor prevalences, is computed assuming an independent distribution. This assumption may not be valid. The aim of the present study was to quantify the maximum extent to which outcome measures of PREVENT may be biased, it the assumed independent distribution of risk factors is incorrect. We therefore calculated to what extent the life expectancy and the potential years of life gained were biased when independent risk factor prevalences were assumed, while they were in fact completely dependent. We used population data, mortality figures and risk factor prevalences from The Netherlands to obtain a realistic estimate of how serious the bias might be. Furthermore, sensitivity analyses were carried out to explore the extent of bias in the case of different risk factor prevalences. The results show that the assumed independence has little impact on the estimated life expectancy and the potential years of life gained, both in the case of the current risk factor prevalences and in the case of higher or lower prevalences. Given that the dependency between risk factors will probably be smaller in reality, we conclude that the assumption of independence may be used since it is not likely to cause substantial bias. This greatly reduces the data requirements necessary as input for simulation models such as PREVENT.@en

REPORTED RELATIVE RISKS associated with smoking differ between studies; these differences may reflect true biological differences between populations or may be research artifacts introduced by differences in factors such as amount smoked or smoking duration. The authors reviewed the literature published before June 1992 on relative risks associated with smoking for heart disease, stroke, lung cancer, and chronic obstructive lung disease. They quantified the effect of variables such as age, amount smoked, and smoking duration on reported relative risks. The main reasons for the variation in reported relative risks were: misclassification of former smokers as never smokers, the use of mortality rate ratios rather than incidence rate ratios, a possible period effect suggesting increasing relative risks over time, and differences in the amount smoked. It is far more likely that these factors are responsible for the observed variation between studies than that the variations reflect true biological differences between populations. Using relative risks from other studies is therefore justified in calculating a population attributable risk if the studies are carefully selected and address factors such as amount smoked and period effects.@en

Study objective - To estimate the prevalence of hypertension in The Netherlands and to quantify the influence of methodological variables on the reported prevalences. Design - A pooled analysis was performed based on reported age specific prevalences of hypertension. A logistic model was used to estimate the probability of hypertension. Main results - The age standardised prevalence of hypertension varies more than fivefold between studies carried out in The Netherlands. The probability of having hypertension was lower if blood pressure was measured at more than one point in time (Odds ratio 0.44 (OR) (95% confidence interval (95% CI) 0.38, 0.51) for men and 0.47 (0.41, 0.54) for women, and if the study was carried out more recently (OR 0.92 (0.91, 0.93) per year). The probability was higher if the study was carried out in a general practice (OR 1.14 (1.03, 1.27) for men and 1.52 (1.36, 1.69) for women). The inclusion of treated people as hypertensive yields contradictory results for men and women. Conclusions - The strong variation in prevalence is explained by methodology and by a period effect indicating a decrease of the prevalence of hypertension over time. Whether this decrease is true or caused by confounding due to unknown or unreported methodological variation over time is unknown. For future studies, a standardised method could reduce the influence of methodological variables and thereby the variation in reported prevalences.@en

The purpose of this study was to determine whether the reported increase in the percentage of never smokers in the group of men born between 1924 and 1938, as observed in survey data in the Netherlands, can be attributed to differential mortality or to misclassification. In a spreadsheet program, the mortality experiences of the men born in 1924 and 1938 were simulated with the use of lifetable techniques. Due to differential mortality, the percentage of true never smokers would be expected to increase from 9% to 9.3% for men born in 1938 and from 9% to 10.3% for men born in 1924. In the survey, the percentage of people who reported that they had never smoked increased from 9% to 36% for the men born between 1924 and 1938. Differential mortality can only explain a very small part of the reported increase in the percentage of "never" smokers. Misclassification of former smokers as never smokers is the most likely cause for the reported increase. This is reason for concern, because even a small percentage of mis classified former smokers may bias the estimated relative risk of mortality associated with current smoking to a considerable extent. Because former smoking status cannot be measured correctly, the percentage of former smokers may be calculated by modeling the percentage of ever smokers. Am J Epidemiol 1994;140:52-7.@en