Kennedy Cruickshank

Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes Principal Results of the Conduit Artery Function Evaluation (CAFE) Study

Background— Different blood pressure (BP)–lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation (CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol±thiazide-based versus amlodipine±perindopril-based therapy) on derived central aortic pressures and hemodynamics. Methods and Results— The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (&Dgr;0.7 mm Hg; 95% CI, −0.4 to 1.7; P=0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen (central aortic systolic BP, &Dgr;4.3 mm Hg; 95% CI, 3.3 to 5.4; P<0.0001; central aortic pulse pressure, &Dgr;3.0 mm Hg; 95% CI, 2.1 to 3.9; P<0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc–defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort (unadjusted, P<0.0001; adjusted for baseline variables, P<0.05). Conclusions— BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.

Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance. An Integrated Index of Vascular Function?

Background—Arterial distensibility measures, generally from pulse-wave velocity (PWV), are widely used with little knowledge of relationships to patient outcome. We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance–tested (GTT) multiethnic population samples. Methods and Results—Participants were randomly sampled from (1) a type 2 diabetes outpatient clinic and (2) primary care population registers, from which nondiabetic control subjects were given a GTT. Brachial blood pressures and Doppler-derived aortic PWV were measured. Mortality data over 10 years’ follow-up were obtained. At any level of systolic blood pressure (SBP), aortic PWV was greater in subjects with diabetes than in controls. Mortality risk doubled in subjects with diabetes (hazard ratio 2.34, 95% CI 1.5 to 3.74) and in those with glucose intolerance (2.12, 95% CI 1.11 to 4.0) compared with controls. For all groups combined, age, sex, and SBP predicted mortality; the addition of PWV independently predicted all-cause and cardiovascular mortality (hazard ratio 1.08, 95% CI 1.03 to 1.14 for each 1 m/s increase) but displaced SBP. Glucose tolerance status and smoking were other independent contributors, with African-Caribbeans experiencing reduced mortality risk (hazard ratio 0.41, 95% CI 0.25 to 0.69). Conclusions—Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population samples. In displacing SBP as a prognostic factor, aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk.

Diabetes and ethnic minorities

The global prevalence of diabetes for all age groups is estimated to be 2.8%. Type 2 diabetes accounts for at least 90% of diabetes worldwide. Diabetes incidence, prevalence, and disease progression varies by ethnic group. This review highlights unique aspects of the risk of developing diabetes, its overwhelming vascular complications, and their management mainly using data among South Asians and African-Caribbeans in the UK but also using non-UK data. It is concluded that although the origin of the ethnic differences in incidence need further clarification, many factors should be amenable to prevention and treatment in all ethnic groups worldwide.

Case-control study of stroke and the quality of hypertension control in north west England.

Abstract Objective: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. Design: Population based matched case-control study. Setting: East Lancashire Health District with a participating population of 388 821 aged (80. Subjects: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure !160 mm Hg or diastolic blood pressure !95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. Main outcome measures: Prevalence of hypertension and quality of control of hypertension (assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). Results: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to <140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (!160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100 000 population aged 40-79. Conclusions: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention. Key messages A case-control study based on the community stroke register and practice records showed a prevalence of hypertension of 61% for stroke patients and 42% in controls Quality of control of blood pressure was clearly related to the risk of stroke, independent of baseline blood pressure Detection and treatment rates of hypertension were high but control of blood pressure to below 150/90 mm Hg in treated hypertensive patients was only 33% in cases and 42% in controls When achieving optimal control of hypertension (to <150/90 mm Hg) in the most at risk and treatable age range (40-79 years) 86 hypertensive patients currently not well controlled need to be treated over five years to prevent one stroke

Nutrient intake trends among African-Caribbeans in Britain: a migrant population and its second generation.

OBJECTIVE To explore British African-Caribbean (AfC) nutrient intake by migration status (place of birth), diet (traditional Caribbean or more European) and age and relate this ecologically to coronary heart disease (CHD) mortality rates. DESIGN Cross-sectional. SETTING Inner-city Manchester, UK. SUBJECTS Two hundred and fifty-five adults of AfC origin aged 25-79 years, randomly sampled from population registers. RESULTS Caribbean-born people (mean age 56, and mean time in Britain 30 years) had significantly lower per cent energy from total and saturated fat than younger British-born AfC people (mean age 29 years) (31.3% vs. 35%, difference in total fat 3.7%, 95%CI 2-5%; in saturated fat 10.9% vs. 12.6%, difference 1.7%, 95%CI 1-2.5%). The Caribbean-born group also ate more fruit (+84g/day-1, 95%CI 36-132g/day-1) and green vegetables (+26 g/day-1, 95%CI 3-49 g/day-1). Men following a traditional diet (> or = 5 days week-1) similarly had a lower per cent energy from fat, at 30.4%, than less traditional eaters, at 33.1% (difference 2.7%, 95%CI 0.7-4.8%). African-Caribbean women, at relatively greater CHD risk than AfC men, had higher body mass indices (BMIs) than AfC men. Compared with national data, AfC subjects consumed some 7% and 5% less energy from total fat and saturated fat, respectively, with over 9% more from carbohydrate. However, there was marked convergence towards the national average in the youngest AfC groups aged 25-34 years, whatever their place of birth. CONCLUSIONS Caribbean birthplace has an independent effect on total fat intake and percentage of energy from fat. Together with higher fruit and vegetable intake, these results are consistent with the dietary fat/antioxidant/CHD hypothesis.

C-reactive protein and the insulin-like growth factor (IGF)-system in relation to risk of cardiovascular disease in different ethnic groups

Inflammatory processes, marked in part by the acute phase reactant C-reactive protein (CRP) and insulin resistance are implicated in atherogenesis. Low insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) concentrations are closely associated with insulin resistance. We examined CRP in ethnic groups with differing risk for cardiovascular disease and type 2 diabetes and its relationship with insulin sensitivity (Homeostasis model assessment (HOMA)-S) and the IGF system. European (n=155), Pakistani (n=108) and African-Caribbean (African Caribbean) (n=177) origin participants were randomly sampled from population registers. All underwent basic anthropometry, glucose tolerance testing and measurement of insulin sensitivity, CRP and other metabolic variables. CRP was significantly lower in African Caribbean men and women than in other ethnic groups. Across all groups CRP correlated negatively with (HOMA-S) (rho=-0.29, P<0.001). Regression analysis which included ethnicity and body mass index (BMI) showed that low HOMA-S (beta=-0.17, P<0.001) and low IGFBP-1 (beta=-0.14, P<0.001) were independently and inversely associated with CRP, but the effect was modified by obesity. In obese subjects insulin sensitivity was not associated with CRP. However, for the whole population, a 2.7 mg/l increase in CRP was associated with a 50% (95% confidence interval (CI) 10-210%) greater risk of WHO defined metabolic syndrome, independent of IGF-I (odds ratio (OR) 0.46 (95% CI 0.22-0.96)), IGFBP-1 (OR 0.58 (0.44-0.76)), female sex (OR 0.43 (0.22-0.84)), NEFA (OR 1.06 (1.03-1.09)) and Pakistani ethnicity. High CRP (as a measure of chronic subclinical inflammation), low IGF-I and low IGFBP-1 are independently associated with the presence of the metabolic syndrome and with insulin resistance. In obese subjects insulin sensitivity is not associated with changes in CRP whilst in non-obese subjects CRP independently contributes to variation in HOMA-S.

Significant ethnic variation in total and free testosterone concentration

objective Measurement of serum testosterone is an integral part of the assessment of men presenting to endocrine clinics. Little is known about the variation of total bound or bioavailable testosterone by ethnic group. The principal determinant of testosterone bioavailability is SHBG, which itself is a marker for insulin sensitivity. Our aim was to examine variations in testosterone and SHBG levels across three ethnic groups in relation to ethnic differences in insulin sensitivity.

Overweight, obesity and high blood pressure in an ethnically diverse sample of adolescents in Britain: the Medical Research Council DASH study

Objectives:To examine the impact of overweight on mean, high normal and high blood pressure in early adolescence, and how this relates to ethnicity and socio-economic status.Design:Cross-sectional study with anthropometric and blood pressure measurements.Setting:A total of 51 secondary schools in London.Sample:A total of 6407 subjects, 11–13 years of age, including 1204 White UK, 698 Other Whites, 911 Black Caribbeans, 1065 black Africans, 477 Indians and 611 Pakistanis/Bangladeshis.Main outcome measures:Mean, high normal (gender, age and height-percentile-specific 90–94th percentile) and high (⩾95th percentile) blood pressure.Results:Based on the International Obesity Task Force age-specific thresholds, 19% of boys and 23% of girls were overweight, and 8% of each were obese. Overweight and obesity were associated with large increases in the prevalence of high normal and high blood pressures compared with those not overweight. The increases in the prevalence of high systolic pressure associated with overweight were as follows: boys, odds ratio 2.50 (95% confidence intervals 1.73–3.60) and girls 3.39 (2.36–4.85). Corresponding figures for obesity were: boys 4.31 (2.82–6.61) and girls 5.68 (3.61–8.95). Compared with their White British peers, obesity was associated with larger effects on blood pressure measures only among Indians, despite more overweight and obesity among black Caribbean girls and overweight among Black African girls. The effect of socio-economic status was inconsistent.Conclusions:The tendency to high blood pressure among adult Black African origin populations was not evident at these ages. These results suggest that the rise in obesity in adolescence portends a rise in early onset of cardiovascular disease across ethnic groups, with Indians appearing to be more vulnerable.

Social stress and depression during pregnancy and in the postnatal period in British Pakistani mothers: A cohort study

Background Depressive disorders are common and disabling among perinatal women. The rates are high in ethnic minority groups. The causes are not known in British Pakistani women. The aim of this study was to estimate the rates, correlates and maintaining factors of perinatal depression in a Pakistani sample in UK. The design used was a cross-sectional two phase population based survey with a prospective cohort study. Methods All women in 3rd trimester attending antenatal clinic were screened with the Edinburgh postnatal depression scale (EPDS). Women scoring 12 or more on EPDS and a random sample of low scorers were interviewed using the Schedules for Assessment in Neuropsychiatry (SCAN) and the Life Events and Difficulties schedule (LEDS). Social support was assessed with the Multidimensional Scale for Perceived Social Support (MSPSS). They were reassessed 6 months after the delivery using the same measures. Results The weighted prevalence of depression was 16.8%. Depressed mothers had more marked non health difficulties (housing, financial and marital). They had less social support and were socially isolated. Marked social isolation and marked non-health related difficulties were independent predictors of depression. Analyses of all the possible risk factors, comparing 26 persistent depressed with 27 depression resolved group showed significant differences in the MSPSS subscales between the two groups. Limitations The study lacked inter-rater reliability testing between the individuals carrying out diagnostic interviews. The study sample did not accurately represent the general population and information about the origins of depression in this group of mothers was limited. Conclusion Depression in British Pakistani mothers is associated with social isolation, poor social support and severe and persistent social difficulties. The findings will have implications in planning suitable services for this group.

A community based stroke register in a high risk area for stroke in north west England.

STUDY OBJECTIVE: To develop a community based stroke register to assess the magnitude of the problem of stroke in an entire health district in a high risk area for stroke. DESIGN: Community based stroke register from general practice data. SETTING: East Lancashire Health Authority with a 1995 population of 534,287. PATIENTS: The stroke register was developed and maintained for one calendar year in East Lancashire between 1 July 1994 and 30 June 1995. Efforts were made to include all patients who had a stroke during this period from participating general practices, using several sources of referral. MAIN RESULTS: Of the districts 118 general practices, 93 (79%) participated fully, covering a population of 405,272. A total of 932 strokes, including 642 first ever cases, were cross checked and confirmed, with only 50% from any single source, mainly the practices. The total stroke incidence rate was 1.60 per 1000 per year, adjusted for the England and Wales 1991 census population. The rate increased considerably with age from 0.88/1000 for ages 50-54 to 20.56/1000 for ages 85-89 years. From 50-74 years, the age specific incidence was higher in men, but overall it was higher in women (1.87; 95% confidence interval 1.67, 2.04 per 1000) than in men (1.31; 1.15, 1.47 per 1000), and slightly lower than in Oxford a decade earlier. The rate also varied in different localities, with higher rates in the central towns of Hyndburn (2.05/ 1000), Blackburn (1.63/1000), and Burnley (1.80/1000) and lowest values in rural areas (1.18/1000 in Pendle). Case fatality from stroke at 28 days was 34% and the hospital admission rate was high at 70%. CONCLUSIONS: The multiple source registration method is required for a stroke register. Stroke incidence in this area was still high and there was considerable variation across the district. Case fatality rates were similar to those in previous studies.