Evaluating different physician's prescribing preference based instrumental variables in two primary care databases: a study of inhaled long-acting beta2-agonist use and the risk of myocardial infarction.

PURPOSE: Instrumental variable (IV) analysis with physician's prescribing preference (PPP) as IV is increasingly used in pharmacoepidemiology. However, it is unclear whether this IV performs consistently across databases. We aimed to evaluate the validity of different PPPs in a study of inhaled long-acting beta2-agonist (LABA) use and myocardial infarction (MI). METHODS: Information on adults with asthma and/or COPD and at least one prescription of beta2-agonist, or muscarinic antagonist was extracted from the CPRD (UK) and the Mondriaan (Netherlands) databases. LABA exposure was considered time-fixed or time-varying. We measured PPPs using previous LABA prescriptions of physicians or proportion of LABA prescriptions per practice. Correlation (r) and standardized difference (SDif) were used to assess assumption of IV analysis. RESULTS: For time-fixed LABA, the IV based on 10 previous prescriptions outperformed the other IVs regarding strength of the IV (r ≥ 0.15) and balance of confounders between IV categories (SDif < 0.10). None of the IVs we considered appeared to be valid for time-varying LABA. In CPRD (n = 490,499), which included approximately 18 times more subjects than Mondriaan (n = 27,459), IVs appeared more valid. LABA was not associated with MI; hazard ratios ranged from 0.86 to 1.18 for conventional analysis, and from 0.61 to 1.24 for the IV analyses with apparent valid IVs. CONCLUSIONS: The validity of physician's prescribing preference as IV strongly depends on how this IV is defined and in which database it is applied. Hence, general recommendations cannot be made, other than to generate several plausible IVs, assess their validity, and report the estimate(s) from apparently valid IVs.

Time trends of period prevalence rates of patients with inhaled long-acting beta-2-agonists-containing prescriptions: a European comparative database study.

BACKGROUND: Inhaled, long-acting beta-2-adrenoceptor agonists (LABA) have well-established roles in asthma and/or COPD treatment. Drug utilisation patterns for LABA have been described, but few studies have directly compared LABA use in different countries. We aimed to compare the prevalence of LABA-containing prescriptions in five European countries using a standardised methodology. METHODS: A common study protocol was applied to seven European healthcare record databases (Denmark, Germany, Spain, the Netherlands (2), and the UK (2)) to calculate crude and age- and sex-standardised annual period prevalence rates (PPRs) of LABA-containing prescriptions from 2002-2009. Annual PPRs were stratified by sex, age, and indication (asthma, COPD, asthma and COPD). RESULTS: From 2002-2009, age- and sex-standardised PPRs of patients with LABA-containing medications increased in all databases (58.2%-185.1%). Highest PPRs were found in men ≥ 80 years old and women 70-79 years old. Regarding the three indications, the highest age- and sex-standardised PPRs in all databases were found in patients with "asthma and COPD" but with large inter-country variation. In those with asthma or COPD, lower PPRs and smaller inter-country variations were found. For all three indications, PPRs for LABA-containing prescriptions increased with age. CONCLUSIONS: Using a standardised protocol that allowed direct inter-country comparisons, we found highest rates of LABA-containing prescriptions in elderly patients and distinct differences in the increased utilisation of LABA-containing prescriptions within the study period throughout the five European countries.

Methodological challenges in monitoring new treatments for rare diseases: lessons from the cryopyrin-associated periodic syndrome registry.

BACKGROUND: The Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare hereditary autoinflammatory diseases and encompass Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID). Canakinumab is a monoclonal antibody directed against IL-1 beta and approved for CAPS patients but requires post-approval monitoring due to low and short exposures during the licensing process. Creative approaches to observational methodology are needed, harnessing novel registry strategies to ensure Health Care Provider reporting and patient monitoring. METHODS: A web-based registry was set up to collect information on long-term safety and effectiveness of canakinumab for CAPS. RESULTS: Starting in November 2009, this registry enrolled 241 patients in 43 centers and 13 countries by December 31, 2012. One-third of the enrolled population was aged < 18; the overall population is evenly divided by gender. Enrolment is ongoing for children. CONCLUSIONS: Innovative therapies in orphan diseases require post-approval structures to enable in depth understanding of safety and natural history of disease. The rarity and distribution of such diseases and unpredictability of treatment require innovative methods for enrolment and follow-up. Broad international practice-based recruitment and web-based data collection are practical.

Sizable variations in circulatory disease mortality by region and country of birth in six European countries.

BACKGROUND: Circulatory disease mortality inequalities by country of birth (COB) have been demonstrated for some EU countries but pan-European analyses are lacking. We examine inequalities in circulatory mortality by geographical region/COB for six EU countries. METHODS: We obtained national death and population data from Denmark, England and Wales, France, the Netherlands, Scotland and Sweden. Mortality rate ratios (MRRs) were constructed to examine differences in circulatory, ischaemic heart disease (IHD) and cerebrovascular disease mortality by geographical region/COB in 35-74 years old men and women. RESULTS: South Asians in Denmark, England and Wales and France experienced excess circulatory disease mortality (MRRs 1.37-1.91). Similar results were seen for Eastern Europeans in these countries as well as in Sweden (MRRs 1.05-1.51), for those of Middle Eastern origin in Denmark (MRR = 1.49) and France (MRR = 1.15), and for East and West sub-Saharan Africans in England and Wales (MRRs 1.28 and 1.39) and France (MRRs 1.24 and 1.22). Low ratios were observed for East Asians in France, Scotland and Sweden (MRRs 0.64-0.50). Sex-specific analyses showed results of similar direction but different effect sizes. The pattern for IHD mortality was similar to that for circulatory disease mortality. Two- to three-fold excess cerebrovascular disease mortality was found for several foreign-born groups compared with the local-born populations in some countries. CONCLUSIONS: Circulatory disease mortality varies by geographical region/COB within six EU countries. Excess mortality was observed for some migrant populations, less for others. Reliable pan-European data are needed for monitoring and understanding mortality inequalities in Europe's multiethnic populations.

Relationship between inflammatory cytokines and uric acid levels with adverse cardiovascular outcomes in patients with stable coronary heart disease.

BACKGROUND: So far it is unclear whether the association between serum uric acid (SUA), inflammatory cytokines and risk of atherosclerosis is causal or an epiphenomenon. The aim of the project is to investigate the independent prognostic relationship of inflammatory markers and SUA levels with adverse cardiovascular outcomes in a patient population with stable coronary heart disease (CHD). METHODS: SUA, C-reactive protein (CRP) and interleukin (IL)-6 were measured at baseline in a cohort of 1,056 patients aged 30-70 years with CHD. Cox proportional hazards model was used to determine the prognostic value of these markers on a combined CVD endpoint during eight year follow-up after adjustment for covariates. RESULTS: For 1,056 patients with stable coronary heart disease aged 30-70 years (mean age 58.9 years, SD 8.0) follow-up information and serum measurements were complete and n = 151 patients (incidence 21.1 per 1000 patients years) experienced a fatal or non-fatal CVD event during follow-up (p-value = 0.05 for quartiles of SUA, p = 0.002 for quartiles of CRP, p = 0.13 for quartiles of IL-6 in Kaplan-Meier analysis). After adjustment for age, gender and hospital site the hazard ratio (HR) for SUA increased from 1.37 to 1.65 and 2.27 in the second, third, and top quartile, when compared to the bottom one (p for trend <0.0005). The HR for CRP increased from 0.85 to 0.98 and 1.64 in the respective quartiles (p for trend 0.02). After further adjustment for covariates SUA still showed a clear statistically significant relationship with the outcome (p for trend 0.045), whereas CRP did not (p for trend 0.10). CONCLUSION: The data suggest that compared to inflammatory markers such as CRP and IL-6 serum uric acid levels may predict future CVD risk in patients with stable CHD with a risk increase even at levels considered normal.

Mortality from circulatory diseases by specific country of birth across six European countries: test of concept.

BACKGROUND: Important differences in cardiovascular disease (CVD) mortality by country of birth have been shown within European countries. We now focus on CVD mortality by specific country of birth across European countries. METHODS: For Denmark, England and Wales, France, The Netherlands, Scotland and Sweden mortality information on circulatory disease, and the subcategories of ischaemic heart disease, and cerebrovascular disease, was analysed by country of birth. Information on population was obtained from census data or population registers. Directly age-standardized rates per 100 000 were estimated by sex for each country of birth group using the WHO World Standard population 2000-25 structure. For differences in the results, at least one of the two 95% confidence intervals did not overlap. RESULTS: Circulatory mortality was similar across countries for men born in India (355.7 in England and Wales, 372.8 in Scotland and 244.5 in Sweden). For other country of birth groups-China, Pakistan, Poland, Turkey and Yugoslavia-there were substantial between-country differences. For example, men born in Poland had a rate of 630.0 in Denmark and 499.3 in England and Wales and 153.5 in France; and men born in Turkey had a rate of 439.4 in Denmark and 231.4 in The Netherlands. A similar pattern was seen in women, e.g. Poland born women had a rate of 264.9 in Denmark, 126.4 in England and Wales and 54.4 in France. The patterns were similar for ischaemic heart disease mortality and cerebrovascular disease mortality. CONCLUSION: Cross-country comparisons are feasible and the resulting findings are interesting. They merit public health consideration.

Gout treatment and comorbidities: a retrospective cohort study in a large US managed care population.

BACKGROUND: Gout prevalence increased in recent years to become one of the most common causes of inflammatory arthritis in most industrialised countries. Comorbidities may affect the disease severity and treatment patterns. We describe the main characteristics of gout patients, gout-related treatment patterns and prevalent comorbidities in a managed care population. METHODS: From the large US PharMetrics Patient-Centric Database, patients aged 20-89 with at least 2 claims for a diagnosis of gout (ICD9 274.xx) and related prescriptions between January 1, 1996 and December 31, 2008 were included. Gout flares were ascertained during follow-up. Sex-specific multivariable Poisson regression models were used to assess factors associated with number of flares. RESULTS: 177,637 gout patients were included (mean age 55.2 years; men 75.6%). Overall, more than half (58.1%) had any of the considered comorbidities; hypertension (36.1%), dyslipidemia (27.0%) and diabetes (15.1%) being the most common. Nonselective NSAIDs were the most commonly dispensed (in 38.7% of patients). Notably, 39% of patients did not receive any prescription medication for gout. Patients with comorbidities were significantly more likely to receive anti-gout prescriptions. During an acute episode the prescription of NSAIDs and colchicine increased; and 29.9% of patients received allopurinol. The risk of flares was associated with cardiometabolic comorbidities and older age in women (highest at age 60-69), while in men it decreased by age. Women with these conditions were 60% more likely to have flares (incidence rate ratio, IRR 1.60;1.48-1.74), while men were 10% (IRR 1.10; 1.06-1.13) more likely. CONCLUSIONS: Comorbidities affected gout treatment patterns and the occurrence and frequency of acute attacks. Cardiometabolic comorbidities, common in this patients' population, were associated with an increased risk of flares.

Frequency and risk factors of gout flares in a large population-based cohort of incident gout.

OBJECTIVE: So far, few data are available to characterize the flare history of patients with gout. The objective of this study was to describe the frequency and risk factors of gout flares with special consideration of the comorbidity. METHODS: A cohort study was conducted in a U.K. general practice database (The Health Improvement Network) including all patients aged 20-89 years diagnosed with incident gout between the years 2000 and 2007. RESULTS: In this study, 23 857 incident gout patients (mean age 61.9 years) were included, overall incidence rate was 2.68 (95% CI 2.65, 2.72) per 1000 person-years. The proportion of patients with at least one flare during the follow-up period (mean 3.8 years) was 36.9% (n=8806). A history of ischaemic heart disease [hazard ratio (HR) 1.12 (95% CI 1.06, 1.19)], hypertension [HR 1.15 (95% CI 1.10, 1.20)] and renal failure [HR 1.33 (95% CI 1.20, 1.48)] were independently associated with a higher risk of a first gout flare. Use of allopurinol at initial gout diagnosis was associated with a lower risk [HR 0.80 (95% CI 0.75, 0.85)]. CONCLUSIONS: Gout flares are relatively common among patients with gout. Some of the underlying cardiometabolic comorbid conditions are themselves independent risk factors for flares, which further contribute to the complexity of treatment of gout flares.

Self-reported never-drinkers in England 1994-2003: characteristics and trends in adults aged 18-54 years.

AIMS: This paper describes prevalences, time-trends and characteristics of self-reported never-drinkers, during the period 1994-2003, focussing particularly on white adults aged 18-54. METHODS: Data on 122,809 adults (18 + ) were obtained from the Health Survey for England (HSfE). Logistic regressions were used to estimate time trends in self-reported never-drinking, and associations between never-drinking and living alone, and educational qualification. Analyses were stratified by gender, age group and period. RESULTS: The overall proportion of white, female never-drinkers was 5.5%, rising monotonically with age. Proportions among men were much lower, with the lowest proportion (1.1%) in the 30-54 age group. Odds of never-drinking increased by 3% per year in those aged 30-54, a trend not explained by any covariates. Smaller increases were seen among those aged 18-29. Never-drinking was strongly associated with living with another adult and with lower qualification. The association with qualification increased over time among young women, and the association with living with another adult increased among men aged 30-54. CONCLUSIONS: Never-drinkers are a significant minority in England, whose prevalence rose, between 1994 and 2003, among adults aged under 55 years. The prevalence varies considerably by age, sex, and social characteristics, and the social discrepancies in never-drinking appear to be widening.

Generalised and abdominal obesity and risk of diabetes, hypertension and hypertension-diabetes co-morbidity in England.

OBJECTIVES: To look at trends in generalised (body mass index (BMI) >or=30 kg m(-2)) and abdominal (waist circumference (WC) >102 cm in men, >88 cm in women) obesity among adults between 1993 and 2003, and to evaluate their association with diabetes, hypertension and hypertension-diabetes co-morbidity (HDC) in England. DESIGN: Analyses of nationally representative cross-sectional population surveys, the Health Survey for England (HSE). SUBJECTS: Non-institutionalised men and women aged >or=35 years. MEASUREMENTS: Interviewer-administered questionnaire (sociodemographic information, risk factors, doctor-diagnosed diabetes), measurements of height and weight to calculate BMI. WC and blood pressure measurements were taken by trained nurses. RESULTS: Generalised obesity increased among men from 15.8% in 1993 to 26.3% in 2003, and among women from 19.3% to 25.8%. Abdominal obesity also increased in both sexes (men: 26.2% in 1993 to 39.0% in 2003; women: 32.4% to 47.0%). In 1994, 1998 and 2003, generalised and abdominal obesity were independently associated with risk of hypertension, diabetes and HDC. The odds of diabetes associated with generalised obesity in 1994, 1998 and 2003 were 1.62, 2.26 and 2.62, respectively, in women and 1.24, 1.82 and 2.10, respectively, in men. Similar differences were observed for hypertension and HDC. Men and women with abdominal obesity also showed a higher risk for diabetes, hypertension and HDC than those with a normal WC. CONCLUSIONS: If current trends in obesity continue then the risk of related morbidities may also increase. This will impact on cardiovascular disease morbidity and mortality, with cost implications for the health service. Therefore there is an urgent need to control the epidemic of obesity.

Domestic physical activity in relationship to multiple CVD risk factors.

BACKGROUND: Public health recommendations emphasize regular participation in moderate intensity physical activity (at least 5 days per week, 30 minutes or more per day), including domestic activities (e.g., heavy housework). The contribution of domestic activities in improving cardiovascular disease risk remains unclear. This cross-sectional study aimed at determining the independent associations of domestic activity and other activity types with multiple cardiovascular disease (CVD) risk factors (resting pulse rate, obesity, total cholesterol, high-density lipoprotein cholesterol, blood pressure, C-reactive protein). METHODS: The sample comprised of 14,836 adults (ages 16 years and over) living in households in England in 2003. Interviews assessed participation in at least moderate intensity physical activity (domestic activity, walking, and sports), and nurses measured blood pressure and took blood samples. Analyses were done in 2006. RESULTS: A total of 24.2% of men and 19.8% of women met the activity recommendations, dropping to a total of 17.6% and 13.0% when domestic activity was excluded. With the exception of systolic blood pressure in women, domestic activity was not related to a favorable profile of any other CVD risk factors. There was a trend for lower body mass index and waist circumference and higher high-density lipoprotein cholesterol with increased participation in walking. Sports participation was related to a favorable profile for all risk factors excluding systolic blood pressure in men and cholesterol and C-reactive protein in women. The odds of being obese (body mass index more than 30 kg/m(2)) were lower with increased participation in walking and sports. CONCLUSIONS: Despite its high prevalence, domestic physical activity was not associated with improvements in CVD risk factors. These results suggest that physical activity recommendations may need to focus on physical activities other than those performed in and around the household.

Cardiovascular surveys: manual of operations.

Cardiovascular disease (CVD) is the leading cause of death and hospitalization in both men and women in nearly all countries of Europe. The most frequent forms of CVD are those of an atherosclerotic origin, mainly ischaemic heart disease, stroke and heart failure. The magnitude of the problem contrasts with the usual paucity and poor quality of data available on incidence and prevalence of CVD, except for few rigorous but limited studies. The objectives of the health interview and health examination surveys (HIS/HES) are to evaluate the frequency and the distribution of the disease, to evaluate trends and treatment effectiveness, to estimate risk factors distribution and prevalence of high risk conditions and to monitor prevention programmes. According to the EUROCISS project (EUROpean Cardiovascular Surveillance Set) recommendations, surveys are aimed at describing the prevalence of the following CVD conditions: myocardial infarction, heart failure, angina pectoris, peripheral arterial disease, stroke, and ischaemic heart disease.HIS and HES were developed to supplement information collected from routine databases and population-based registers to implement consistent public health policies. HIS can be repeated periodically in a new sample of the population, or can follow up over time the population recruited at baseline. Procedures and methods to collect information from participants include self-administered questionnaires, direct interviewer-administered questions and telephone interviews. A minimum set of questions to be administered every year, along with a longer, more detailed module to be administered periodically are recommended to evaluate CVD prevalence. The addition of HES provides more detailed and objective information that can be used to improve estimates regarding prevalence of both risk factors and disease status. The selection of more specialized CVD-specific tests will depend on the objective the survey is designed to achieve, the assumed response rate and the cost and time considerations. For HES on CVD the minimum required is to perform the following measurements: height, weight, blood pressure, waist circumference, total and high density lipoprotein-cholesterol and glucose assay in a nonfasting blood sample. The next appropriate step would be to perform an electrocardiogram. High costs usually make HES difficult to carry out. Standardization of measurements, training of personnel and quality control are essential to assure reliable data. A high response rate is extremely important, as nonrespondents tend to have different health characteristics from the rest of the sample and their omission therefore results in bias. This manual of operations is intended for health professionals and policy makers and provides a standardized and simple model for the implementation of a CVD survey.

Improvement in hypertension management in England: results from the Health Survey for England 2003.

OBJECTIVE: To evaluate the mean levels of blood pressure and hypertension (> or = 140 mmHg systolic or > or = 90 mmHg diastolic pressure or on treatment for hypertension) in the adult English population, and to evaluate any changes in the efficacy of hypertension management between 1994 and 2003. DESIGN/METHODS: Cross-sectional surveys. England, 2003. A nationally representative sample of 8834 non-institutionalized adults (aged > or = 16 years). Rates of awareness, treatment and control of hypertension. RESULTS: Since 1994, mean systolic blood pressure has fallen by 1.6 and 4.3 mmHg in male and female adults, respectively. The rates of awareness and treatment have increased, and control rates (< 140 mmHg systolic and < 90 mmHg diastolic) among hypertensive men and women have approximately doubled to 21.5 and 22.8%, respectively. Of those on treatment for hypertension, the majority (56%) are on two or more agents compared with 40% in 1994 and 1998. CONCLUSION: Hypertension management has improved greatly since 1994, with more awareness, treatment and control. Nevertheless, in 2003 the majority of hypertensive adults in England had blood pressure levels above the currently recommended targets.

Levels of dyslipidaemia and improvement in its management in England: results from the Health Survey for England 2003.

OBJECTIVE: To evaluate blood lipid levels in the adult English population and to report changes in the use and efficacy of lipid-lowering treatment between 1998 and 2003. DESIGN: Cross-sectional surveys. Participants Nationally representative sample of 8,269 non-institutionalized adults (>or= 16 years) living in England, taking part in the Health Survey for England 2003. MEASUREMENTS: Mean levels of total, HDL, non-HDL and total : HDL cholesterol ratio; prevalence of hypercholesterolaemia; use of lipid-lowering agents and lipid levels among those on treatment; blood pressure. Information on smoking and history of cardiovascular events and diabetes were recorded by the interviewer. RESULTS: In 2003 69.9% of adults had a total cholesterol >or= 5 mmol/l and 6.2% reported lipid-lowering treatment. Treatment rates among those with a total cholesterol >or= 5 mmol/l and a history of coronary heart disease or stroke, hypertension or diabetes were 71.1%, 32.7% and 50.9%, respectively in men; and 55.8%, 22.4% and 50.0% in women. In all these groups, more than half of those treated were controlled (< 5 mmol/l). Only small changes in levels of dyslipidaemia were seen since 1998 (when 67.5% of adults had a total cholesterol >or= 5 mmol/l), but use of lipid-lowering treatment has more than doubled and control rates have increased by approximately fourfold. CONCLUSIONS: Treatment and control rates of lipids have improved importantly between 1998 and 2003 but remain suboptimal. Reductions in major cardiovascular events are likely to result from these changes and may be further enhanced by adherence to the new general practitioner contract.

Vitamin D concentrations among people aged 65 years and over living in private households and institutions in England: population survey.

BACKGROUND: vitamin D deficiency among older people results in poor bone and muscle health and an increased risk of fractures. In the UK, government initiatives and the launch of the Osteoporosis Strategy have been in place since 1998, highlighting the importance of adequate levels of vitamin D for its prevention. The aim of this analysis is to assess vitamin D status and examine associations of deficiency with risk factors among older people in England. METHODS: a valid vitamin D sample was obtained from 1,766 informants as part of the Health Survey for England (HSE) 2000, a nationally representative survey of people aged 65 and over living in institutions and private households in England. RESULTS: among both men and women in institutions, the prevalence of vitamin D deficiency was higher and mean serum vitamin D levels were significantly lower than among those in private households. Regression analyses showed that women were more likely to be vitamin D deficient than men (odds ratio (OR) 2.1) and deficiency was associated with limiting longstanding illness (OR 3.57), manual social classes (OR 2.4), poor general health (OR 1.92) and body mass index<25 kg/m2 (OR 2.02), and was 67% more likely among informants in the winter/autumn. Overall, the results show no significant improvements in vitamin D status in comparison to earlier National Diet and Nutrition Survey (NDNS) results. CONCLUSION: vitamin D deficiency exists at worrying levels among those aged 65 years and over. Further action is needed to alert health professionals about the risks related to vitamin D deficiency and extend the provision of prevention and treatment programmes targeted to those in need.

An international comparative study of blood pressure in populations of European vs. African descent.

BACKGROUND: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. METHODS: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). RESULTS: The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. CONCLUSIONS: These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.

Birth weight and blood pressure in childhood: results from the Health Survey for England.

Findings of previous reports relating low birth weight with raised blood pressure in childhood and adolescence have been inconsistent. The present study uses cross-sectional data from a series of nationally representative annual surveys--the Health Survey for England--between 1995 and 2002, totaling a sample of 15 629 children aged 5 to 15. A significant negative relationship between birth weight, in quartiles or dichotomized as low (<2.5 kg) and normal (> or =2.5 kg) and systolic blood pressure was apparent. Linear regression analyses confirmed these findings. When current weight was included in the model, the strength of the relationship increased. An interaction term between birth weight and current weight was not significant. A life-course plot for those aged 13 to 15 (n=3900), converting the weight measurements at birth and as a teenager to standard deviation scores to make the regression coefficients comparable, showed the importance of weight gain on blood pressure (1 standard deviation increase in weight from birth to age 13 to 15 was associated with an increase in systolic blood pressure of 0.8 mm Hg). Separating those with low and normal birth weight demonstrated that the increase in weight from birth to adolescence had an effect on blood pressure in both those with low and normal birth weight. Postnatal changes in size have a more important effect on blood pressure in childhood and adolescence than birth weight. Reducing the prevalence of overweight among children may reduce their systolic blood pressure importantly and, particularly among children with lower birth weight, the prevalence of hypertension later in life.

Hypertension management and control among English adults aged 65 years and older in 2000 and 2001.

OBJECTIVE: To describe blood pressures, and hypertension and its management among older people. DESIGN: Two combined annual cross-sectional surveys. SETTING: England 2000 and 2001. PARTICIPANTS: Nationally-representative sample of 3513 non-institutionalized people aged more than 64 years (elderly). MAIN OUTCOME MEASURES: (1). Use of antihypertensive agents, and hypertension according to two definitions: receiving blood pressure decreasing treatment, or either: systolic blood pressure > or= 160 mmHg or diastolic blood pressure > or= 90 mmHg (old); or systolic blood pressure > or= 140 mmHg or diastolic blood pressure > or=90 mmHg (new). (2). Rates of treatment and control (old: < 160/90 mmHg; new: < 140/85 mmHg). (3). Isolated systolic hypertension stage 1 (systolic blood pressure > or= 140-159 mmHg and diastolic blood pressure < 90 mmHg), or stage 2 (systolic blood pressure > or= 160 mmHg and diastolic blood pressure < 90 mmHg). RESULTS: In 2000/2001, 62 and 81% of elderly adults were hypertensive according to the old and new definitions, respectively. Among those with hypertension (new definition) treatment and control rates were 56 and 19% (control rates among those treated were 36% in men and 30% in women). Of those treated, 54% were receiving one drug, 35% were receiving two, and 10% were receiving three or more drugs. Among untreated hypertensive individuals, 23% had increased systolic and diastolic pressures, 76% had isolated systolic hypertension and 1% had isolated diastolic hypertension. CONCLUSIONS: These data suggest that, according to current guidelines more than 67% of older English adults should receive antihypertensive medication. To pre-empt this situation, population-based strategies to reduce the current rate of increase in blood pressure throughout adult life should be urgently implemented. Only then will the current epidemic of hypertension among the elderly, with the huge cost associated with its management and adverse cardiovascular sequelae, be averted.

Hypertension treatment and control in five European countries, Canada, and the United States.

Levels of hypertension treatment and control have been noted to vary between Europe and North America, although direct comparisons with similar methods have not been undertaken. In this study, we sought to estimate the relative impact of hypertension treatment strategies in Germany, Sweden, England, Spain, Italy, Canada, and the United States by using sample surveys conducted in the 1990s. Hypertension was defined as a blood pressure of 160/95 mm Hg or 140/90 mm Hg, plus persons taking antihypertensive medication. "Controlled hypertension" was defined as a blood pressure less than threshold among persons taking antihypertensive medications. Among persons 35 to 64 years, 66% of hypertensives in the United States had their blood pressure controlled at 160/95 mm Hg, compared with 49% in Canada and 23% to 38% in Europe. Similar discrepancies were apparent at the 140/90 mm Hg threshold, at which 29% of hypertensives in the United States, 17% in Canada, and

Measuring nicotine intake in population surveys: comparability of saliva cotinine and plasma cotinine estimates.

Both plasma and saliva cotinine levels have been reported in surveys of smoking behavior, and it is of interest to know how closely these two measures correspond. Plasma and saliva specimens were gathered from a sample of 605 respondents in the 1998 Health Survey for England and assayed for cotinine by a well-proven gas chromatographic method. Plasma and saliva cotinine concentrations were highly correlated (r=.99). On average, concentrations in saliva were 25% higher than in plasma, and this ratio applied both at the low levels attributable to passive smoking and across the range of active smoking values. The ratio was somewhat lower in younger people than in older people and also varied significantly by body mass index but did not differ by gender. Calculation of the limits of agreement revealed substantial uncertainty in the predicted plasma value corresponding to a given saliva cotinine, and vice versa. For comparisons across subjects, the mean plasma cotinine level corresponding to a mean saliva cotinine level can be estimated with confidence, but at the level of the individual, considerable predictive uncertainty remains.