Search

Objectives: Hypertension phenotypes differ between Africans and Europeans, with a greater prevalence of low renin salt-sensitive hypertension and greater predisposition to adverse cardiac remodelling in Africans. To elucidate the roles of inheritance and environment in determining hypertension phenotypes in sub-Saharan Africans and white-Europeans, we compared phenotypes in white individuals in the UK (n = 132) and in African individuals in the UK (n = 158) and Nigeria (n = 179)., Methods: Biochemistry, blood pressure, left ventricular structure (echocardiography) and 24-h urinary collections of sodium and potassium were measured., Results: Twenty-four-hour urinary sodium/potassium ratio was lower in individuals living in Europe (both African and white: 2.32 ± 0.15 and 2.28 ± 0.17) than in individuals in Nigeria (4.09 ± 0.26, both P < 0.001) reflecting proportionately higher potassium intake in Europeans (African or white) than African residents. Plasma renin was lower in Africans irrespective of residency than white Europeans, but aldosterone was higher in Africans in Europe than those in Africa (466.15 ± 32.95 vs. 258.60 ± 17.42 pmol/l, P < 0.001). Left ventricular mass index adjusted for blood pressure and other confounders was greatest in Africans in Europe (103.27 ± 2.32 g/m) compared with those in Africa (89.28 ± 1.98 g/m) or white Europeans (86.77 ± 2.63 g/m, both P < 0.001)., Conclusion: Despite a similar low renin state in African origin individuals living in Europe and Africa, a higher aldosterone level, possibly related to higher potassium intake or other environmental factors, may contribute to greater cardiac remodelling in Africans in Europe.

Objectives: Raised vascular function measures are associated with adverse maternal and perinatal outcomes in low-risk pregnancy. This study aimed to evaluate the association between longitudinal vascular function parameters and adverse outcome in pregnant women with chronic hypertension, and to assess whether these measures vary according to baseline parameters such as black ethnicity., Methods: This was a nested cohort study of women with chronic hypertension and a singleton pregnancy recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs lAbetalol as antihypertensive treatment) study at one of three UK maternity units. Women had serial pulse-wave analyses performed using the Arteriograph®, while in a sitting position, from 12 weeks' gestation onwards. Statistical analysis was performed using random-effects logistic regression models. Longitudinal vascular parameters were compared between women who developed superimposed pre-eclampsia (SPE) and those who did not, between women who delivered a small-for-gestational-age (SGA) infant (birth weight < 10 th centile) and those who delivered an infant with birth weight ≥ 10 th centile and between women of black ethnicity and those of non-black ethnicity., Results: The cohort included 97 women with chronic hypertension and a singleton pregnancy, of whom 90% (n = 87) were randomized to antihypertensive treatment and 57% (n = 55) were of black ethnicity, with up to six (mean, three) longitudinal vascular function assessments. SPE was diagnosed in 18% (n = 17) of women and 30% (n = 29) of infants were SGA. In women who developed subsequent SPE, compared with those who did not, mean brachial systolic blood pressure (SBP) (148 mmHg vs 139 mmHg; P = 0.002), mean diastolic blood pressure (DBP) (87 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (139 mmHg vs 128 mmHg; P = 0.001) and mean augmentation index (AIx-75) (29% vs 22%; P = 0.01) were significantly higher across gestation. In women who delivered a SGA infant compared to those who delivered an infant with birth weight ≥ 10 th centile, mean brachial SBP (146 mmHg vs 138 mmHg; P = 0.001), mean DBP (86 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (137 mmHg vs 127 mmHg; P < 0.0001) and mean pulse-wave velocity (9.1 m/s vs 8.5 m/s; P = 0.02) were higher across gestation. No longitudinal differences were found in vascular function parameters in women of black ethnicity compared with those of non-black ethnicity., Conclusion: There were persistent differences in vascular function parameters and brachial blood pressure throughout pregnancy in women with chronic hypertension who later developed adverse maternal or perinatal outcome. Further investigation into the possible clinical use of these findings is warranted. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Background Malaria exposure in childhood may contribute to high blood pressure ( BP ) in adults. We used sickle cell trait ( SCT ) and α + thalassemia, genetic variants conferring partial protection against malaria, as tools to test this hypothesis. Methods and Results Study sites were Kilifi, Kenya, which has malaria transmission, and Nairobi, Kenya, and Jackson, Mississippi, where there is no malaria transmission. The primary outcome was 24-hour systolic BP. Prevalent hypertension, diagnosed using European Society of Hypertension thresholds was a secondary outcome. We performed regression analyses adjusting for age, sex, and estimated glomerular filtration rate. We studied 1127 participants in Kilifi, 516 in Nairobi, and 651 in Jackson. SCT frequency was 21% in Kilifi, 16% in Nairobi, and 9% in Jackson. SCT was associated with -2.4 (95% CI , -4.7 to -0.2) mm Hg lower 24-hour systolic BP in Kilifi but had no effect in Nairobi/Jackson. The effect of SCT in Kilifi was limited to 30- to 59-year-old participants, among whom it was associated with -6.1 mm Hg ( CI , -10.5 to -1.8) lower 24-hour systolic BP. In pooled analysis allowing interaction by site, the effect of SCT on 24-hour systolic BP in Kilifi was -3.5 mm Hg ( CI , -6.9 to -0.1), increasing to -5.2 mm Hg ( CI , -9.5 to -0.9) when replacing estimated glomerular filtration rate with urine albumin to creatinine ratio as a covariate. In Kilifi, the prevalence ratio for hypertension was 0.86 ( CI , 0.76-0.98) for SCT and 0.89 ( CI , 0.80-0.99) for α + thalassemia. Conclusions Lifelong malaria protection is associated with lower BP in Kilifi. Confirmation of this finding at other sites and elucidating the mechanisms involved may yield new preventive and therapeutic targets.

Background: In the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs. We did three substudies to assess the mechanisms underlying this superiority and the pathogenesis of resistant hypertension., Methods: PATHWAY-2 was a randomised, double-blind crossover trial done at 14 UK primary and secondary care sites in 314 patients with resistant hypertension. Patients were given 12 weeks of once daily treatment with each of placebo, spironolactone 25-50 mg, bisoprolol 5-10 mg, and doxazosin 4-8 mg and the change in home systolic blood pressure was assessed as the primary outcome. In our three substudies, we assessed plasma aldosterone, renin, and aldosterone-to-renin ratio (ARR) as predictors of home systolic blood pressure, and estimated prevalence of primary aldosteronism (substudy 1); assessed the effects of each drug in terms of thoracic fluid index, cardiac index, stroke index, and systemic vascular resistance at seven sites with haemodynamic monitoring facilities (substudy 2); and assessed the effect of amiloride 10-20 mg once daily on clinic systolic blood pressure during an optional 6-12 week open-label runout phase (substudy 3). The PATHWAY-2 trial is registered with EudraCT, number 2008-007149-30, and ClinicalTrials.gov, number NCT02369081., Findings: Of the 314 patients in PATHWAY-2, 269 participated in one or more of the three substudies: 126 in substudy 1, 226 in substudy 2, and 146 in substudy 3. Home systolic blood pressure reduction by spironolactone was predicted by ARR (r 2 =0·13, p<0·0001) and plasma renin (r 2 =0·11, p=0·00024). 42 patients had low renin concentrations (predefined as the lowest tertile of plasma renin), of which 31 had a plasma aldosterone concentration greater than the mean value for all 126 patients (250 pmol/L). Thus, 31 (25% [95% CI 17-33]) of 126 patients were deemed to have inappropriately high aldosterone concentrations. Thoracic fluid content was reduced by 6·8% from baseline (95% CI 4·0 to 8·8; p<0·0001) with spironolactone, but not other treatments. Amiloride (10 mg once daily) reduced clinic systolic blood pressure by 20·4 mm Hg (95% CI 18·3-22·5), compared with a reduction of 18·3 mm Hg (16·2-20·5) with spironolactone (25 mg once daily). No serious adverse events were recorded, and adverse symptoms were not systematically recorded after the end of the double-blind treatment. Mean plasma potassium concentrations increased from 4·02 mmol/L (95% CI 3·95-4·08) on placebo to 4·50 (4·44-4·57) on amiloride (p<0·0001)., Interpretation: Our results suggest that resistant hypertension is commonly a salt-retaining state, most likely due to inappropriate aldosterone secretion. Mineralocorticoid receptor blockade by spironolactone overcomes the salt retention and resistance of hypertension to treatment. Amiloride seems to be as effective an antihypertensive as spironolactone, offering a substitute treatment for resistant hypertension., Funding: British Heart Foundation and UK National Institute for Health Research., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The potential association between sickle cell trait (SCT) and increased arterial stiffness/blood pressure (BP) has not been evaluated in detail despite its association with stroke, sudden death, and renal disease. We performed 24-hour ambulatory BP monitoring and arterial stiffness measurements in adolescents raised in a malaria-free environment in Kenya. Between December 2015 and June 2016, 938 randomly selected adolescents (ages 11-17 years) who had been continuous residents of Nairobi from birth were invited to participate in the study. Standard clinic BP measurement was performed, followed by 24-hour ambulatory BP monitoring and arterial stiffness measurement using an Arteriograph24 (TensioMed Ltd., Budapest, Hungary) device. SCT status was determined using DNA genotyping in contemporaneously collected blood samples. Of the 938 adolescents invited to participate, 609 (65%) provided complete data for analysis. SCT was present in 103 (15%). Mean 24-hour systolic and diastolic BPs were 116 (standard deviation (SD), 11.5) mm Hg and 64 (SD, 7) mm Hg, respectively, in children with SCT and 117 (SD, 11.4) mm Hg and 64 (SD, 6.8) mm Hg, respectively, in non-SCT children. Mean pulse wave velocity (PWV) was 7.1 (SD, 0.8) m/second and 7.0 (SD, 0.8) m/second in SCT and non-SCT children, respectively. We observed no differences in PWV or in any clinic or ambulatory BP-derived measures between adolescents with and without SCT. These data suggest that SCT does not independently influence BP or PWV., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches., Methods and Results: We performed a 1-year, double-blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0-16), patients were randomly assigned to initial monotherapy (losartan 50-100 mg or hydrochlorothiazide 12.5-25 mg crossing over at 8 weeks), or initial combination (losartan 50-100 mg plus hydrochlorothiazide 12.5-25 mg). In phase 2 (weeks 17-32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33-52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7-6.0 mm Hg) less over 32 weeks ( P <0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg [range: -0.4 to 2.8 mm Hg], P =0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events., Conclusions: Initial combination therapy can be recommended for patients with BP >150/95 mm Hg., Clinical Trial Registration: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Vascular and lung function develop and decline over the life course; both predict cardiovascular events and mortality but little is known of how they develop over time. We analysed their relationship in a multiethnic cohort study to test whether lung function from early adolescence to young adulthood affected vascular indices., Methods: 'DASH' (http://dash.sphsu.mrc.ac.uk) included 6643 children aged 11-13 years in 2003; a representative 10% sample (n = 665) participated in a pilot follow-up in 2013. Psychosocial, anthropometric, blood pressure (BP), and lung function measures were collected in both surveys; aortic pulse wave velocity (PWV) and augmentation index (AIx) were measured at aged 21-23 years. Relationships between forced expiratory volume Z-scores in 1 s (zFEV1), after global initiative-ethnic adjustments and BP, PWV, and AIx were tested in linear regression and general estimating statistical models., Results: In total, 488 people with complete data were included. At 11-13 years, SBP was positively associated with zFEV1 (coefficient = 1.90, 95% confidence interval 1.11-2.68, P < 0.001); but not at 21-23 years. The 10-year increase in zFEV1 was associated with rise in SBP (1.38, 0.25-1.51, P < 0.05) in mixed effect models adjusted for age, sex, ethnicity, waist to height ratio, employment, reported racism, smoking, and alcohol use but DBP change was unrelated. In fully adjusted models, neither PWV nor central AIx were associated with zFEV1 at 11-13 years or 21-23 years (P > 0.05)., Conclusion: Forced expiratory volume change is positively and independently associated with SBP change from adolescence to young adulthood, suggesting earlier lung function plays important roles in SBP development. Vascular indices were unrelated to lung function or its change.

Background: Recent studies have discovered that α-globin is expressed in blood vessel walls where it plays a role in regulating vascular tone. We tested the hypothesis that blood pressure (BP) might differ between normal individuals and those with α + thalassemia, in whom the production of α-globin is reduced., Methods and Results: The study was conducted in Nairobi, Kenya, among 938 adolescents aged 11 to 17 years. Twenty-four-hour ambulatory BP monitoring and arterial stiffness measurements were performed using an arteriograph device. We genotyped for α + thalassemia by polymerase chain reaction. Complete data for analysis were available for 623 subjects; 223 (36%) were heterozygous (-α/αα) and 47 (8%) were homozygous (-α/-α) for α + thalassemia whereas the remaining 353 (55%) were normal (αα/αα). Mean 24-hour systolic BP ±SD was 118±12 mm Hg in αα/αα, 117±11 mm Hg in -α/αα, and 118±11 mm Hg in -α/-α subjects, respectively. Mean 24-hour diastolic BP ±SD in these groups was 64±8, 63±7, and 65±8 mm Hg, respectively. Mean pulse wave velocity (PWV)±SD was 7±0.8, 7±0.8, and 7±0.7 ms -1 , respectively. No differences were observed in PWV and any of the 24-hour ambulatory BP monitoring-derived measures between those with and without α + thalassemia., Conclusions: These data suggest that the presence of α + thalassemia does not affect BP and/or arterial stiffness in Kenyan adolescents., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

Objectives: In this study, we examined the effects of birth weight (BWT) and early life socioeconomic circumstances (SEC) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) among Jamaican young adults., Study Design and Setting: Longitudinal study of 364 men and 430 women from the Jamaica 1986 Birth Cohort Study. Information on BWT and maternal SEC at child's birth was linked to information collected at 18-20 years old. Sex-specific multilevel linear regression models were used to examine whether adult SBP/DBP was associated with BWT and maternal SEC., Results: In unadjusted models, SBP was inversely related to BWT z-score in both men (β, -0.82 mm Hg) and women (β, -1.18 mm Hg) but achieved statistical significance for women only. In the fully adjusted model, one standard deviation increase in BWT was associated with 1.16 mm Hg reduction in SBP among men [95% confidence interval (CI): 2.15, 0.17; P = 0.021] and 1.34 mm Hg reduction in SBP among women (95% CI: 2.21, 0.47; P = 0.003). Participants whose mothers had lower SEC had higher SBP compared with those with mothers of high SEC (β, 3.4-4.8 mm Hg for men, P < 0.05 for all SEC categories and 1.8-2.1 for women, P > 0.05)., Conclusion: SBP was inversely related to maternal SEC and BWT among Jamaican young adults., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial., (© 2014 American Heart Association, Inc.)

Aims: To study the effect of the insulin-like growth factor (IGF) system on growth, adiposity and systolic blood pressure (SBP) in early life in British-born South Asian (SA) and White European (WE) children., Methods: The effect of IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) over the first 4 years in 204 healthy SA and WE children was investigated by mixed linear regression modelling. This enabled inclusion of all follow-up observations and adjustment for repeated measures., Results: At birth, SA babies were shorter and lighter than WE babies. Over 4 years, SA ethnicity was associated with lower height, weight and body mass index (BMI) standard deviation score (SDS), higher subscapular/triceps skinfold thickness (Ss/Tr SFT) and lower SBP (all p < 0.01). IGF-1 was associated with greater height (p = 0.03), weight (p < 0.001) and BMI SDS (p < 0.001), and IGFBP-3 with greater weight SDS (p < 0.001), BMI SDS (p = 0.001), Ss/Tr SFT (p = 0.003) and SBP (p = 0.023)., Conclusions: Over this first 4-year period of life, SA ethnicity was associated with being shorter, lighter, having more superficial truncal adiposity and lower SBP. IGFBP-3 (and not IGF-1) was independently associated with both superficial truncal adiposity and SBP, suggesting that IGFBP-3 is a potential metabolic and cardiovascular marker in healthy children in the early years of life.

Background: Some studies suggest that blood pressure (BP)-lowering effects of commonly used antihypertensive drugs differ among ethnic groups. However, differences in the response to second-line therapy have not been studied extensively., Methods: In the BP-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA), BP levels of European (n = 4,368), African (203), and South-Asian- (132) origin patients on unchanged monotherapy (atenolol or amlodipine) and/or on second-line therapy (added thiazide or perindopril) were compared. Interaction between ethnicity and BP responses (defined as end BP minus start of therapy BP) to both first- and second-line therapies were assessed in regression models after accounting for age, sex, and several other potential confounders., Results: BP response to atenolol and amlodipine monotherapy differed among the three ethnic groups (interaction test P = 0.05). Among those allocated atenolol monotherapy, black patients were significantly less responsive (mean systolic BP (SBP) difference +1.7 (95% confidence interval: -1.1 to 4.6) mm Hg) compared to white patients (referent). In contrast, BP response to amlodipine monotherapy did not differ significantly by ethnic group. BP responses to the addition of second-line therapy also differed significantly by ethnic group (interaction test P = 0.004). On adding a diuretic to atenolol, BP lowering was similar among blacks and South-Asians as compared to whites (referent). However, on addition of perindopril to amlodipine, BP responses differed significantly: compared to whites (SBP difference -1.7 (-2.8 to -0.7) mm Hg), black patients had a lesser response (SBP difference 0.8 (-2.5 to 4.2) mm Hg) and South-Asians had a greater response (SBP difference -6.2 (-10.2 to -2.2) mm Hg)., Conclusions: We found important differences in BP responses among ethnic groups to both first- and second-line antihypertensive therapies.

The cause of ethnic differences in cardiovascular disease remains a scientific challenge. Blood pressure tracks from late childhood to adulthood. We examined ethnic differences in changes in blood pressure between early and late adolescence in the United Kingdom. Longitudinal measures of blood pressure, height, weight, leg length, smoking, and socioeconomic circumstances were obtained from London, United Kingdom, schoolchildren of White British (n=692), Black Caribbean (n=670), Black African (n=772), Indian (n=384), and Pakistani and Bangladeshi (n=402) ethnicity at 11 to 13 years and 14 to 16 years. Predicted age- and ethnic-specific means of blood pressure, adjusted for anthropometry and social exposures, were derived using mixed models. Among boys, systolic blood pressure did not differ by ethnicity at 12 years, but the greater increase among Black Africans than Whites led to higher systolic blood pressure at 16 years (+2.9 mm Hg). Among girls, ethnic differences in mean systolic blood pressure were not significant at any age, but while systolic blood pressure hardly changed with age among White girls, it increased among Black Caribbeans and Black Africans. Ethnic differences in diastolic blood pressure were more marked than those for systolic blood pressure. Body mass index, height, and leg length were independent predictors of blood pressure, with few ethnic-specific effects. Socioeconomic disadvantage had a disproportionate effect on blood pressure for girls in minority groups. The findings suggest that ethnic divergences in blood pressure begin in adolescence and are particularly striking for boys. They signal the need for early prevention of adverse cardiovascular disease risks in later life.

Background: Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension., Methods and Results: CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, -0.1 mm Hg [95% CI, -1.8 to 1.6], P=0.9; change in brachial pulse pressure, -0.02 mm Hg [95% CI, -1.6 to 1.6], P=0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, -0.5 mm Hg [95% CI, -2.3 to 1.2], P=0.5; change in aortic pulse pressure, -0.4 mm Hg [95% CI, -1.9 to 1.0], P=0.6) and had no influence on augmentation index (change in augmentation index, -0.4%; 95% CI, -1.7 to 0.8; P=0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, -1.3 to 1.8; P=0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure-lowering treatment strategy in the factorial design., Conclusions: Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA.

Objective: The objective of this study was to investigate early influences of postnatal growth on blood pressure (BP) in healthy, British-born South Asian and European origin infants. We tested the hypotheses that South Asian infants would be smaller in all body dimensions (length and weight) with higher relative truncal skinfold thickness at birth, and that increased (central) adiposity and accelerated growth up to 1 year would be associated with higher BP in both ethnic groups., Patients and Methods: Five hundred and sixty infants were followed prospectively from birth to 3 and/or 12 months with measures of anthropometry and resting BP, compared against a UK 1990 growth reference, and analysed using regression methods., Results: Marked differences in birth size persisted, as expected, between European and South Asian babies, but with a sexual dichotomy: South Asian boys were smaller in all anthropometric parameters (P < 0.001), including skinfolds (P < 0.05), than European boys, but South Asian girls, although smaller in length and weight, had similar skinfolds to European girls and thus a slightly larger subscapular skinfold thickness relative to birth weight [1.3 versus 1.2, mean difference 0.07, 95% confidence interval (CI) 0.0009-0.14, P = 0.047]. The dichotomy persisted postnatally; South Asian boys showed a striking early increase in weight and length compared with European boys, associated with significant accrual of subscapular fat (6.1 versus 5.3 mm, mean difference 0.8, 95% CI 0.3-1.3, P = 0.003). In gender and ethnicity adjusted regression models, infants with the largest weight standard deviation score (SDS) increases in the first 3 months had the highest 12-month systolic BP (beta = 2.4, 95% CI 0.5-4.2, P = 0.01), while those with the greatest birth length (beta = 0.7, 95% CI 0.05-1.4, P = 0.04) but the smallest changes in length over 3-12 months (beta = -0.57, 95% CI -0.95 to -0.19, P = 0.004) had the highest diastolic BP., Conclusions: Ethnic and gender differences in growth and adiposity present in early infancy include truncal fat preservation in South Asian girls from birth, which in boys is related to rapid early weight gain. Weight gain during the first 3 months appears to drive the rise in systolic BP to 1 year, itself a likely driver of later BP.

Objectives: In this first large-scale study of ethnic differences in blood pressure (BP) among British adolescents, we examine the differences in BP levels in adolescence and the extent to which age, sex, body size and stage of maturation affect any observed differences., Method: A total of 6365 11-13 year olds (including 1189 white, 907 black Caribbeans and 1056 black Africans, 473 Indians, 605 Pakistanis and Bangladeshis, and 548 of mixed ethnicity) had systolic blood pressure (SBP) and diastolic blood pressure (DBP), anthropometry and pubertal stage measured in 2003., Results: Compared with their white UK counterparts, black Caribbean and African boys were taller, and black Caribbean and African girls were taller, larger and matured earlier. Except for DBP among Indian girls, BP in minority groups was generally lower than in white UK children. Adjusted for age, height and body mass index, mean SBP was 109.1 mmHg (95% confidence interval 108.4, 109.8) and DBP 65.7 mmHg (65.2, 66.3) among white UK boys. Black Caribbean boys had lower SBP (-2.0; -3.2, -0.9 mmHg) and DBP (-1.5; -2.3, -0.6), and black African (-2.3; -3.4, -1.2) and mixed ethnicity (-1.6; -2.9, -0.3) boys had lower SBP. Adjusted SBP was 108.5 (107.8, 109.3) and DBP was 67.5 mmHg (66.9, 68.1) among white UK girls. Pakistani (-1.8; -3.2, -0.4) and black African (-1.1; -1.9, -0.3) girls had lower SBP and Indian girls (1.2; 0.1, 2.4) had higher DBP. Unlike African American girls, late puberty was not associated with higher BP in minority groups., Conclusion: At these ages, the ethnic-specific patterns in BP in adulthood were not observed. Apart from higher DBP for Indian girls, BP in minority groups was generally lower than their white UK counterparts. Targeting intervention in adolescence may be a critical opportunity for preventing ethnic differences in BP in later life.

Background: The determinants of differences in blood pressure that emerge in adolescence between black Americans of predominantly African descent and white Americans of predominantly European descent are unknown. One hypothesis is related to intrauterine and early childhood growth. The role of early blood pressure itself is also unclear. We tested whether differences in birth weight and in carefully standardized subsequent measures of weight, height, and blood pressure from 0 to 4 or 5 years were related to black/white differences in blood pressure in adolescence., Methods and Results: Two Bogalusa cohorts who had complete follow-up data on birth weights and early childhood and adolescent anthropometric and blood pressure measures were pooled. One hundred eighty-five children (48 black and 47 white boys and 41 black and 49 white girls) were followed up and studied after 15 to 17 years. Birth weights were a mean 443 and 282 g lower in black boys and girls, respectively, than in whites (P<0.001). Blood pressures in adolescence were 3.4/1.9 and 1.7/0.6 mm Hg higher, respectively, and tracked from early childhood. In regression analyses, birth weight accounted for the ethnic difference in adolescent blood pressure, which was also independently predicted, in decreasing impact order, by adolescent height, adolescent body mass index, and systolic blood pressure at 4 to 5 years and inversely by growth from 0 to 4 to 5 years., Conclusions: If these results can be replicated in larger and independent samples, they suggest that efforts to improve intrauterine growth in black infants as well as lessen weight gain in adolescence might substantially reduce excess high blood pressure/hypertension in this ethnic group.

Prospective comparisons of different drug classes have shown that differences in blood pressure control, rather than differences between drug classes, have the over-riding influence on overall outcome. The same studies have also reinforced the need, in the majority of patients, to use combinations of drugs in order to achieve the target of <140/85 mmHg. By contrast, most patients in routine practice receive single agents and consequently fail to achieve target blood pressure. This failure reflects in part the emphasis in individual studies and subsequent guidelines on comparison of individual drugs. In this article we show how the consistency of both theory and a broad range of evidence permits a didactic approach to combination therapy. Our advice is based on the growing recognition that essential hypertension and its treatment fall into two main categories. Younger Caucasians usually have renin-dependent hypertension that responds well to angiotensin-converting-enzyme inhibition or angiotensin receptor blockade (A) or ss blockade (B). Most other patients have low-renin hypertension that responds better to calcium channel blockade (C) or diuretics (D). These latter drugs activate the renin system rendering patients responsive to the addition of renin suppressive therapy. Coincidence of the initials of these main drug classes with the first four letters of the alphabet permits an AB/CD rule, according to which recommended combinations are one drug from each of the "AB" and "CD" categories of drugs. However, the diabetogenic potential of the older "B" and "D" classes leads us to advise against combining "B" and "D" in older patients, and to recommend "A" + "C" + "D" as standard triple therapy for resistant hypertension.

Aims/hypothesis: Insulin resistance/hyperinsulinaemia is implicated in the development of cardiovascular disease and diabetes but its role and causal pathways are not clear. We tested the hypothesis that the insulin-like growth factor system is independently associated with cardiovascular risk within susceptible populations based on previous reports of the links between low circulating insulin-like growth factor binding protein-1 concentrations and increased macrovascular disease in Type II (non-insulin-dependent) diabetes mellitus., Methods: In a population-based study 272 subjects (142 subjects of European and 130 Pakistani of origin) underwent a 75 g oral glucose tolerance test and standardised anthropometry. Fasting concentrations of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured and were related to 2-h glucose tolerance test status. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA)., Results: Insulin-like growth factor binding protein-1 was significantly lower in subjects with impaired glucose tolerance when compared with normal glucose tolerance in both ethnic groups (Europeans F = 6.7, p = 0.002 and Pakistanis F = 4.4, p = 0.01). Multiple linear regression modelling showed that insulin-like growth factor binding protein-1 was independently associated with 2-h glucose (beta = 0.16, p = 0.009) and logistic regression indicated a 40% reduction in risk of impaired glucose tolerance for every 2.7 ng/ml increase in the insulin-like growth factor binding protein-1 concentration [odds ratio 0.6 (CI = 0.49-0.71), p = 0.001)]. In addition, insulin-like growth factor binding protein-1 was significantly correlated negatively with several established cardiovascular factors, and positively with insulin sensitivity., Conclusions/interpretation: Insulin-like growth factor binding protein-1 is closely related to risk factors for diabetes and cardiovascular disease in people of European and Pakistani origin. It has potential use as a marker of (hepatic) insulin resistance in clinical intervention studies and further implicates the insulin-like growth factor system in the development of macrovascular disease.

Objective: To assess the public health burden from high blood pressure and the current status of its detection and management in four African-origin populations at emerging or high cardiovascular risk., Design: Cross-site comparison using standardized measurement and techniques., Setting: Rural and urban Cameroon; Jamaica; Manchester, Britain., Subjects: Representative population samples in each setting. African-Caribbeans (80% of Jamaican origin) and a local European sample in Manchester., Main Outcome Measures: Cross-site age-adjusted prevalence; population attributable risk., Results: Among 1,587 men and 2,087 women, age-adjusted rates of blood pressure > or =160 or 95 mmHg or its treatment rose from 5% in rural to 17% in urban Cameroon, despite young mean ages, to 21% in Jamaica and 29% in Caribbeans in Britain. Treatment rates reached 34% in urban Cameroon, and 69% in Jamaican- and British-Caribbean-origin women. Sub-optimal blood pressure control (> 140 and 90 mmHg) on treatment reached 88% in European women. Population attributable risks (or fractions) indicated that up to 22% of premature all-cause, and 45% of stroke mortality could be reduced by appropriate detection and treatment. Additional benefit on just strokes occurring on treatment could be up to 47% (e.g. in both urban Cameroon men and European women) from tighter blood pressure control on therapy. Cheap, effective therapy is available., Conclusion: With mortality risk now higher from non-communicable than communicable diseases in sub-Saharan Africa and elsewhere, systematic measurement, detection and genuine control of hypertension once treated can go hand-in-hand with other adult health programmes in primary care. Cost implications are not great. The data from this collaborative study suggest that such efforts should be well rewarded.

Unlike the brain, oxygen extraction for the heart is almost maximal at rest, so lowering coronary filling pressure (DBP) below the lower limit of autoregulation with antihypertensive drugs can lead to myocardial ischemia. This situation is exacerbated by the presence of coronary stenosis, which if more than 85% means that coronary flow reserve is virtually zero (particularly in the presence of LVH). Such patients experience a fall in coronary flow and ischemia when DBP is acutely lowered to less than the mid-80s. Ischemic episodes on the 24-hour Holter monitor in treated hypertensives are often immediately preceded by a hypotensive episode. The "J-curve" debate has been going for over 20 years. Those that deny a J-curve relationship between treated DBP and myocardial infarction (MI) quote the continuous DBP/MI relationship seen in the large cohort of MRFIT screenees (with ischemic patients weeded out). However, the actual MRFIT (and similar HDFP) study patients with abnormal ECGs (ischemia or LVH), in contrast to those with normal ECGs, in the special-care group experienced an excess of coronary events associated with a DBP 5 mmHg lower than the referred-care group. Other studies, including the prospective HOT study, have indicated that ischemic hypertensives gain optimal results when DBP is lowered to the mid- to low 80s; below this level, the frequency of MI increases. This treatment-induced J-curve should not be confused with Nature's untreated J-curve, which results from the association of a low DBP (wide pulse-pressure) due to aging, noncompliant arteries, and an increasing frequency of ischemic events. A reasonable conclusion from most treatment studies (including HOT) is that in nonischemic hypertensives there is little point in lowering DBP below the mid- to low 80s in terms of MI prevention--though it is safe to do so. In contrast, ischemic hypertensives should not have their DBP lowered to less than the mid- to low 80s for fear of increasing the risk of MI.

It is well recognized that end-stage renal disease (ESRD) is associated with accelerated and malignant hypertension. The association of renal disease and what is considered as normal blood pressure is still not clear. The present study examined the temporal relation between blood pressure and renal function reflected by serum creatinine in a biracial (black-white) community-based population enrolled in the Bogalusa Heart Study. The study included 662 young adults aged 19 to 32 years, (white men, n = 188; white women, n = 289; black men, n = 67; and black women, n = 118) who were followed for an average of 7.4 years. In black men, partial correlation adjusted for age, body mass index, serum glucose, uric acid, and cigarette smoking showed that baseline systolic and diastolic blood pressure are not significantly related to baseline serum creatinine, but significantly related to serum creatinine at follow-up (r = 0.38, P = .008 and r = 0.42, P = .003, respectively). Multivariate regression analysis further showed a significant prediction of serum creatinine at follow-up by baseline systolic and diastolic blood pressure (0.031 mg/dL and 0.037 mg/dL rise in follow-up serum creatinine for every 10 mm Hg increase in systolic (P = .000) and diastolic (P = .001) blood pressure at baseline, but not the other way around. Other race and sex groups did not show such significant temporal relations. We conclude that in young black men, higher blood pressure levels within normal range precede and explain part of the increase in serum creatinine, a measure of decline in renal function. Thus, our results underscore the beneficial effect of maintaining blood pressure levels lower than what is considered as the upper normal limit, particularly in black men.

Coronary flow is maintained in the face of changing perfusion pressure (approximates to diastolic blood pressure [DBP]) by the process of autoregulation. A normal coronary artery is able to dilate fivefold (coronary flow reserve of 5); by contrast, coronary flow reserve falls in the presence of left ventricular hypertrophy [LVH] and/or coronary artery disease. Thus a fall in DBP that is normally well tolerated causes a fall in coronary flow, ECG changes, and left ventricular dysfunction in the presence of LVH and coronary artery disease. Such high-risk patients exhibit a J-curve relationship between DBP and death from coronary artery disease; lowering DBP (phase 5) to below the mid 80s would be imprudent in such patients.

Coronary flow is normally autoregulated so that within wide limits of changes in perfusion pressure (which approximate to diastolic BP) blood flow to the heart remains constant. Thus, as perfusion pressure falls, the coronary arterioles dilate to maintain flow; under basal conditions a five-fold increase in coronary flow can occur, i.e. a flow reserve of five. Coronary flow reserve is markedly impaired in the presence of severe coronary artery stenosis and/or LVH. In the presence of severe stenosis and LVH a fall in perfusion pressure (DBP), which would be normally well tolerated, results in a fall of coronary flow, ECG changes and ventricular dysfunction (fall in ejection fraction instead of the usual increase). The above mechanisms underlie the J-curve relationship between DBP and myocardial infarction (MI) in high risk hypertensives. In the absence of overt coronary artery disease (CAD) and LVH, the lower the DBP the better. However in the presence of CAD and LVH lowering the DBP (phase 5) to below the low-mid 80s results in an increased frequency of MI.

An investigation of restriction fragment length polymorphisms (RFLPs) and association with blood pressure was carried out for the candidate genes coding for renin (REN) and atrial natriuretic peptide (ANP). The relationship between blood pressure, REN and ANP gene RFLPs was tested in a population of black Afro-Caribbean and white European subjects sampled randomly from family practice registers. Upper and lower quintiles for diastolic blood pressure were selected for analysis. Digests of DNA were prepared from leucocytes and RFLPs were determined using Southern blotting analysis with REN and ANP gene probes. There were highly significant ethnic differences found for BglI, Bg/lI and TaqI polymorphisms with 5'REN probe and for BglI polymorphism with an ANP probe. There was also an association between blood pressure and the BglI/REN polymorphism in Afro-Caribbeans but not with any other polymorphisms studied in either ethnic group. The findings show significant ethnic RFLP differences at the gene loci for both renin and ANP and provide evidence for a possible link between variations within or close to the renin gene and elevated blood pressure in Afro-Caribbeans.

The frequency of non-insulin-dependent diabetes mellitus (NIDDM) and of high blood pressure (or hypertension) is higher in some ethnic groups than in others for reasons that remain unclear. To investigate the mechanisms leading to these ethnic differences, plasma C-peptide and insulin concentrations were measured after overnight fast and during an oral glucose tolerance test in subjects aged 45-74 years sampled from the practice lists of two north west London health centres. Ethnic group was defined by grandparental origin as Afro-Caribbean in 106, Gujerati Indian in 107, and white European in 101. The total age-adjusted prevalence of NIDDM was 29% in the Afro-Caribbean, 30% in the Gujerati, and 3% in the white groups, respectively. Fasting C-peptide and insulin concentrations increased from the subgroup with normal glucose tolerance, through impaired glucose tolerance, to new NIDDM, and were lower again in subjects with known NIDDM. The odds ratio for new NIDDM was 1.87 (95% confidence interval 1.26-2.77) per 1 SD increase in fasting C-peptide, which was the most powerful independent indicator of new NIDDM (p = 0.0005) and accounted for the effect of ethnic group. Fasting insulin had a similarly strong effect. There was no relation between any index of insulin secretion and blood pressure or hypertension. There were differences among the ethnic groups in the C-peptide response relative to the insulin response. These results suggest that factors determining insulin secretion and its hepatic clearance, possibly including dietary fat, are the main causes of ethnic variation in rates of new NIDDM.

Objective: To examine the hypothesis that a J curve relation between blood pressure and death from coronary heart disease is confined to high risk subjects with myocardial infarction., Design: Cohort longitudinal epidemiological study with biennial examinations since 1950., Setting: Framingham, Massachusetts, USA., Subjects: 5209 subjects in the Framingham study cohort followed up by a person examination approach., Main Outcome Measures: Coronary heart disease deaths and non-cardiovascular disease deaths in men and women with or without myocardial infarction relative to blood pressure., Results: Among subjects without myocardial infarction non-cardiovascular disease deaths were twice to three times as common as coronary heart disease deaths. Furthermore, there was no significant relation between non-cardiovascular disease death and diastolic or systolic blood pressure. Also coronary heart disease deaths were linearly related to diastolic and systolic blood pressures. Among high risk patients (that is, people with myocardial infarction but free of congestive heart failure) death from coronary heart disease was more common than non-cardiovascular disease death. There was a significant U shaped relation between coronary heart disease death and diastolic blood pressure. Although there was an apparent U shaped relation between coronary heart disease death and systolic blood pressure, it did not attain statistical significance when controlling for age and change in systolic blood pressure from the pre-myocardial infarction level. None of the above conclusions changed when adjustments were made for risk factors such as serum cholesterol concentration, antihypertensive treatment, and left ventricular function. The U shaped relation between diastolic blood pressure and high risk subjects existed for both those given antihypertensive treatment and those not., Conclusions: These data suggest that an age and sex independent U curve relation exists for diastolic blood pressure and coronary heart disease deaths in patients with myocardial infarction but not for low risk subjects without myocardial infarction. The relation seems to be independent of left ventricular function and antihypertensive treatment.

The present single-blind, randomised, cross-over, placebo-controlled study was set up to compare the first-dose effects upon blood pressure (BP) and cerebral blood flow (CBF, measured by Xenon inhalation) of a single oral dose of atenolol 50 mg and enalapril 5 mg in ten hypertensive patients receiving a thiazide diuretic. It was found that a) the timing and degree of fall in BP after the first dose of atenolol and enalapril on a diuretic background were similar and generally not associated with symptoms or a fall in CBF, and b) dizziness, which is sometimes associated with the first-dose effect of ACE inhibitors in hypertensives on diuretics, can occasionally occur accompanied by a substantial fall (43%) in CBF in the absence of marked falls in systolic blood pressure. It is suggested that the latter event may be linked to a disturbance of cerebral autoregulation in part dependent on localised renin-angiotensin systems.

The effects or oral atenolol (100 mg once/day) and metoprolol (100 mg once/day, 100 mg twice/day and 300 mg once/day) have been compared with placebo on the heart rate and systolic blood pressure responses to exercise in 5 healthy volunteers. The drugs were given for 5 days in a double blind randomised fashion with each volunteer receiving each dose of drug. Measurements were made after the first dose on day 1 and after 5 days of dosing. The results on both heart rate and systolic blood pressure showed that overall (over a 24 h period) after acute (day 1) or after chronic (5 days) dosing, atenolol 100 mg once/day, metoprolol 100 mg twice/day and 300 mg once/day, were equivalent as beta-adrenoceptor blocking doses. Thus milligram for milligram atenolol and metoprolol do not produce equivalent blockade on the cardiovascular system of man.

A screening survey was conducted among factory workers, aged 15-64 years, in Birmingham, England to investigate ethnic differences in blood pressure. One-thousand and forty-nine subjects (784 men, 265 women) were screened, representing 79% of the eligible population. Mean systolic and diastolic blood pressures generally did not differ between men of black West Indian (n = 173), local white (n = 439) or Asian (n = 172) origin, when matched by 10-year age groups. Analysis of covariance using age as the covariate revealed that, overall, Asian men had significantly lower systolic but higher diastolic pressures than the other ethnic groups. The proportion of men arbitrarily defined as hypertensive (greater than or equal to 160 mmHg systolic or greater than or equal to 95 diastolic or blood pressures below this figure whilst receiving antihypertensive therapy) was 26% of West Indians, 22% of whites and 17% of Asians, but these were not significantly different when age was accounted for. Black West Indian women (n = 101) did have higher diastolic pressure than white women (n = 164), but this difference was dependent on body mass index. Overall, systolic pressures in women were not significantly different. These findings differ from those consistently reported from the United States.

The results of several large studies of hypertension and follow up studies on insured people have indicated that the lower the blood pressure the better for longevity. These studies excluded subjects with overt ischaemia. More recently long term studies of hypertension that included patients with more severe forms of hypertension and did not exclude those with overt ischaemia have shown a J shaped relation between diastolic blood pressure during treatment and myocardial infarction; the lowest point (the J point) was at a diastolic blood pressure (phase V) between 85 and 90 mm Hg. The J curve seems to be independent of treatment, pulse pressure, and the degree of fall in diastolic blood pressure and is unlikely to be caused by poor left ventricular function. The most probable explanation is that subjects who have severe stenosis of the coronary artery as well as hypertension have a poor coronary flow reserve, which makes the myocardium vulnerable to coronary perfusion pressures that are tolerated by patients without ischaemia, particularly at high heart rates. An optimal diastolic blood pressure (phase V) for such patients is about 85 mm Hg, though particular caution is appropriate when treating very old patients (84 and over) and patients aged 60-79 who have isolated systolic hypertension.

Chronic smoking, particularly in hypertensives, is associated with an increased frequency of cerebral infarction and subarachnoid haemorrhage; cerebral blood flow (CBF) is also decreased in chronic smokers. The acute effects of smoking upon CBF are less clear. The present study in six volunteers investigated the immediate effects of smoking (and inhaling) three cigarettes, each separated by a 2 hr gap, upon heart rate, blood pressure (BP) and CBF assessed by xenon inhalation and flow velocities in the middle cerebral artery by transcranial Doppler ultrasound. Smoking caused significant increases in heart rate, BP and middle cerebral artery flow velocities, and a significant fall in CBF (individual falls in hemispherical flow could be as great as 40%). These haemodynamic effects are probably caused by nicotine-induced changes in catecholamine release. The possible clinical significance of the BP and CBF changes induced by acute smoking in high-risk groups is discussed.

To investigate whether the lower the blood pressure (BP) the better the prognosis for the patient with moderate-to-severe hypertension, an assessment was made of 902 patients who received the beta 1-selective beta-blocker atenolol (median dose 100 mg a day), either alone or with other antihypertensive agents, for up to 10 years (mean 6.1). 91 died, 40 from myocardial infarction, 21 from stroke, and 30 from other causes. Initial BP was a poor predictor of mortality from myocardial infarction, whereas treated systolic blood pressure (SBP) was a strong predictor. There was a J-shaped relation, confined to those with evidence of ischaemic heart disease, between frequency of death from myocardial infarction and treated DBP (phase V); the frequency was lowest at treated DBP of 85-90 mm Hg and rose with treated DBP on either side of this range.

A prospective controlled study investigated the effects of oral contraceptives on blood pressure in 485 women who were between 17 and 46 years of age and had blood pressures of less than 140/90 mmHg at entry. The women were divided into seven groups depending on the chosen method of contraception: intrauterine device or barrier method (control group): ethinyl oestradiol 30 micrograms plus levonorgestrel 150 micrograms (Microgynon-30 or Ovranette); norethisterone 350 micrograms (Micronor); norgestrel 75 micrograms (Neogest); norethisterone oenanthate 200 mg intramuscularly every 2 months for the first 6 months, then every 3 months thereafter; ethinyl oestradiol 30 micrograms plus ethynodiol diacetate 2 mg (Conova-30); and ethynodiol diacetate 500 micrograms (Femulen). Blood pressures were measured every 3 months by the family planning clinic nurse under standardized conditions using an Elag-Köln automatic sphygmomanometer. After one year, blood pressure had risen significantly (P less than 0.05) in the 137 women taking ethinyl oestradiol plus levonorgestrel (mean systolic and diastolic rises 6.4 and 2.7 mmHg respectively) and in the 91 women taking ethinyl oestradiol plus ethynodiol diacetate (mean systolic and diastolic rises 6.2 and 3.0 mmHg respectively). The 94 women taking the progestogen-only preparations and the 143 women in the control group showed no increases in blood pressure. These data were confirmed after 2 years of follow-up.

Longitudinal evidence on the association between air pollution and blood pressure (BP) in adolescence is scarce. We explored this association in an ethnically diverse cohort of schoolchildren. Sex-stratified, linear random-effects modelling was used to examine how modelled residential exposure to annual average nitrogen dioxide (NO2), particulate matter (PM2.5, PM10) and ozone (O3), measures in μg/m3, associated with blood pressure. Estimates were based on 3,284 adolescents; 80% from ethnic minority groups, recruited from 51 schools, and followed up from 11–13 to 14–16 years old. Ethnic minorities were exposed to higher modelled annual average concentrations of pollution at residential postcode level than their White UK peers. A two-pollutant model (NO2 & PM2.5), adjusted for ethnicity, age, anthropometry, and pubertal status, highlighted associations with systolic, but not diastolic BP. A μg/m3 increase in NO2 was associated with a 0.30 mmHg (95% CI 0.18 to 0.40) decrease in systolic BP for girls and 0.19 mmHg (95% CI 0.07 to 0.31) decrease in systolic BP for boys. In contrast, a 1 μg/m3 increase in PM2.5 was associated with 1.34 mmHg (95% CI 0.85 to 1.82) increase in systolic BP for girls and 0.57 mmHg (95% CI 0.04 to 1.03) increase in systolic BP for boys. Associations did not vary by ethnicity, body size or socio-economic advantage. Associations were robust to adjustments for noise levels and lung function at 11–13 years. In summary, higher ambient levels of NO2 were associated with lower and PM2.5 with higher systolic BP across adolescence, with stronger associations for girls. [ABSTRACT FROM AUTHOR]