Hypertension: Smith G

Anonymous00047, Fitzgerald DA, Massie RJ, Nixon GM, Jaffe A, Wilson A, Landau LI, Twiss J, Smith G, Wainwright C, Harris M. · Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW, Australia. · Med J Aust. · Pubmed #19012558 links to  free full text

Abstract: Chronic neonatal lung disease (CNLD) is defined as a supplemental oxygen requirement beyond 36 weeks' postmenstrual age, with more severely affected infants requiring oxygen beyond a full-term-equivalent age. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who develop hypoxia in air. There is a lack of data on the most appropriate minimum mean target oxygen saturation (Spo(2)) level. Reflecting a variety of clinical practices and infant comorbidities (frequency of oxygen desaturation, presence of pulmonary hypertension, retinopathy of prematurity, and adequacy of growth), the minimum mean target range for Spo(2) during overnight oximetry should be 93%-95%. The effect of supplemental oxygen on carbon dioxide retention should be considered before deciding on an oxygen flow. Most infants with CNLD are not ready for discharge until their supplemental oxygen requirement is < or = 0.5 litres per minute delivered through a nasal cannula. The safety of short-term disconnection from supplemental oxygen should be assessed before discharge. Assessment of oxygenation during sleep with continuous overnight oximetry or polysomnography is recommended when weaning infants from supplemental oxygen. Discontinuation of oxygen therapy is based on clinical assessments and documentation of adequate oxygenation in room air. There is limited objective evidence on which to base recommendations.

Wofford MR, Smith G, Minor DS. · Department of Medicine, Division of General Internal Medicine/Hypertension, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. · Curr Hypertens Rep. · Pubmed #18474182 No free full text.

Abstract: Hypertension causes a significant disease burden in all racial and ethnic groups and is directly attributable to excess weight in most cases. The relationship between increasing body mass index and hypertension prevalence has been recognized for decades. Epidemiologic studies clearly demonstrate the correlation between body weight and blood pressure in obese and lean populations. Most patients with hypertension are overweight or obese, and loss of excess weight lowers blood pressure. Although the epidemiologic relationship is clear, the understanding of mechanisms linking hypertension and weight gain is still evolving. Lifestyle modifications and specific pharmacologic agents address many of the known mechanisms; however, blood pressure remains difficult to control in obese hypertensive patients. This review highlights the association of obesity and hypertension, identifies potential mechanisms for this association, and describes nonpharmacologic and pharmacologic strategies that offer potential benefits for the obese patient with hypertension.

Wheeler D, Vimalachandra D, Hodson EM, Roy LP, Smith G, Craig JC. · Centre for Kidney Research and Cochrane Renal Group, NHMRC Centre of Clinical Research Excellence in Renal Medicine, The Children's Hospital at Westmead, Sydney, NSW, Australia. · Arch Dis Child. · Pubmed #12876164 links to  free full text

Abstract: AIMS: To evaluate the benefits and harms of treatments for vesicoureteric reflux in children. METHODS: Meta-analyses of randomised controlled trials using a random effects model. Main outcome measures were incidence of urinary tract infection (UTI), new or progressive renal damage, renal growth, hypertension, and glomerular filtration rate. RESULTS: Eight trials involving 859 evaluable children comparing long term antibiotics with surgical correction of reflux (VUR) and antibiotics (seven trials) and antibiotics compared with no treatment (one trial) were identified. Risk of UTI by 1-2 and 5 years was not significantly different between surgical and medical groups (relative risk (RR) by 2 years 1.07; 95% confidence interval (CI) 0.55 to 2.09, RR by 5 years 0.99; 95% CI 0.79 to 1.26). Combined treatment resulted in a 60% reduction in febrile UTI by 5 years (RR 0.43; 95% CI 0.27 to 0.70) but no concomitant significant reduction in risk of new or progressive renal damage at 5 years (RR 1.05; 95% CI 0.85 to 1.29). In one small study no significant differences in risk for UTI or renal damage were found between antibiotic prophylaxis and no treatment. CONCLUSION: It is uncertain whether the identification and treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.

Gerdts E, Roman MJ, Palmieri V, Wachtell K, Smith G, Nieminen MS, Dahlöf B, Devereux RB. · Institute of Medicine, University of Bergen, Norway. · J Hum Hypertens. · Pubmed #15103312 No free full text.

Abstract: To assess the influence of age on changes in left ventricular (LV) mass and geometry during antihypertensive treatment, we related age to clinical and echocardiographic findings before and after 4 years of antihypertensive treatment in a subset of 560 hypertensive patients without known concurrent disease in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which randomized patients to blinded losartan- or atenolol-based treatment. Patients >/=65 years (older group) included more women and patients with isolated systolic hypertension or albuminuria (all P<0.05). Compared to patients <65 years, older patients had higher pulse pressure, LV mass, and prevalence of concentric hypertrophy at baseline (78 vs 69 mmHg, 234 vs 224 g, and 28 vs 16%, respectively, all P<0.01), while the mean blood pressure did not differ. Over 4 years, reductions in LV mass and the mean blood pressure were similar in both groups, but older patients more often had residual hypertrophy (31 vs 15%, P<0.001) with a preponderance of eccentric geometry. In multivariate analysis of 4-year change in LV mass controlling for baseline mass, larger hypertrophy reduction was associated with losartan treatment, while age, gender, body mass index, and 4-year change in pulse pressure and albuminuria did not enter (Multiple R (2)=0.40, P<0.001). Thus, in up-to-80-year-old hypertensive patients with left ventricular hypertrophy, age did not significantly attenuate hypertrophy reduction during antihypertensive treatment, although residual hypertrophy was more prevalent in older patients as a consequence of higher initial LV mass.

Wachtell K, Dahlöf B, Rokkedal J, Papademetriou V, Nieminen MS, Smith G, Gerdts E, Boman K, Bella JN, Devereux RB. · Department of Medicine, Copenhagen County University Hospital, Glostrup, Denmark. · Am Heart J. · Pubmed #12486431 No free full text.

Abstract: BACKGROUND: Patients with hypertension have different types of left ventricular (LV) geometry, but the impact of blood pressure (BP) reduction on LV geometry change during antihypertensive treatment remains unclear. METHODS: Two-dimensional and M-mode echocardiograms were recorded at baseline in 853 unmedicated patients with stage II to III hypertension and LV hypertrophy determined by electrocardiography (Cornell voltage duration > or =2440 mV x ms or modified Sokolow-Lyon criteria: SV1 + RV5/RV6 >38 mV) after 14 days of placebo treatment. Follow-up echocardiography was done after 1 year of blinded treatment with either losartan or atenolol, in some cases supplemented with thiazide and calcium antagonist to reach target a BP of 140/90 mm Hg. RESULTS: Baseline systolic/diastolic BP were reduced from 174 +/- 20/95 +/- 11 to 151 +/- 19/84 +/- 11 mm Hg. LV mass was reduced from 234 +/- 56 to 207 +/- 51 g and relative wall thickness from 0.41 +/- 0.07 to 0.38 +/- 0.06 (all P <.001). Prevalence of concentric LV hypertrophy decreased from 24% to 6%, eccentric LV hypertrophy from 46% to 37%, and concentric LV remodeling from 10% to 6%; normal geometry increased from 20% to 51%. A shift toward lower LV mass and relative wall thickness was found, as approximately 73% of those with concentric LV remodeling at baseline shifted to normal geometric pattern, whereas only 7% of those with normal pattern at baseline shifted to concentric LV remodeling. Of patients with concentric LV hypertrophy at baseline, 34% shifted to eccentric LV hypertrophy, whereas only 3% with eccentric LV hypertrophy at baseline had concentric LV hypertrophy. Furthermore, multiple regression analysis showed that Doppler stroke volume reduction was a significant correlate of LV mass reduction (beta = 0.108, P <.001) independent of BP, heart rate change, and assigned drug treatment. CONCLUSIONS: Antihypertensive treatment reduces LV mass and decreases the prevalence of LV hypertrophy and concentric LV remodeling. Additional control of Doppler stroke volume potentiates the effect of BP reduction on LV mass regression independent of the BP reduction per se.

Wachtell K, Palmieri V, Olsen MH, Gerdts E, Papademetriou V, Nieminen MS, Smith G, Dahlöf B, Aurigemma GP, Devereux RB. · Copenhagen County University Hospital, Glostrup, Denmark. · Circulation. · Pubmed #12105163 links to  free full text

Abstract: BACKGROUND: We have shown that hypertensive patients with left ventricular (LV) hypertrophy have decreased LV midwall mechanics, but the effect of antihypertensive therapy remains unclear. METHODS AND RESULTS: Echocardiograms were recorded at baseline in 679 hypertensive patients and ECG LV hypertrophy and repeated yearly during 3 years of blinded treatment to achieve target blood pressures (BPs) of 140/90 mm Hg. On average, BP was reduced from 174+/-21 to 147+/-19 over 95+/-11 to 82+/-10 mm Hg and LV mass from 234+/-56 to 194+/-50 g. Endocardial fractional shortening (FS) decreased slightly, whereas midwall FS increased from 15.4+/-2.0% to 16.8+/-2.1% and stress-corrected midwall FS increased from 97+/-13 to 105+/-12% (all P<0.001). Change in midwall FS was related inversely to change in LV mass (LVM), relative wall thickness (RWT), and diastolic BP and directly to change in Doppler stroke volume (SV, all P<0.001). Multivariate analysis showed that change in MWS was independently inversely related to changes in LVM (beta=-0.211), RWT (beta=-0.334, all P<0.001), and diastolic BP (beta=-0.088, P<0.05) and directly related to SV (beta=0.192, P<0.001) with control for blinded therapy. Change in stress-corrected midwall shortening was inversely independently associated with changes in LVM (beta=-0.153) and RWT (beta=-0.562) and directly with changes in SV (beta=0.145) and systolic BP (beta=0.s221, all P<0.001) with control for blinded therapy. CONCLUSIONS: Antihypertensive therapy reduced LVM and increased LV midwall shortening and contractility with a small decrease in LV chamber function and significant increase in SV. Change in systolic LV performance was independently associated inversely with change in LVM, RWT, and BP and directly with change in SV.

Masson R, Nicklin SA, Craig MA, McBride M, Gilday K, Gregorevic P, Allen JM, Chamberlain JS, Smith G, Graham D, Dominiczak AF, Napoli C, Baker AH. · BHF GCRC, University of Glasgow, 126 University Place, Glasgow, G12 8TA United Kingdom. · Hypertension. · Pubmed #19221212 No free full text.

Abstract: Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis.

Smith G, Reyes JT, Russell JL, Humpl T. · Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada. · Chest. · Pubmed #19118264 No free full text.

Abstract: BACKGROUND: Maximal cardiopulmonary exercise testing (CPX) is valuable to quantifying functional capacity in patients with pulmonary hypertension (PH), but information on CPX in children is limited possibly because of safety concerns. The purpose of this study was to examine the safety of CPX in pediatric patients with PH. METHODS: Data were obtained retrospectively from patients referred for CPX at our institution between January 2001 and September 2007. Patients with a 6-min walk distance < 275 m were excluded. Exercise test complications were grouped according to ischemic ECG changes, presence of arrhythmia, and oxygen desaturation at peak exercise and were graded as mild, moderate, or severe. RESULTS: Twenty-seven patients (4 with idiopathic PH, 23 with secondary PH), 12.5 years of age (range, 6.9 to 18 years), participated in 64 CPX sessions. The mean (+/- SD) peak oxygen uptake was 23.3 +/- 5.4 mL/kg/min, with a mean decrease in arterial oxygen saturation to 85% +/- 15.7% at peak exercise. Mild arrhythmia was detected in 30% of the patients. ST-segment depression was graded as mild (19%) or moderate (1.5%). There were no significant adverse events, such as syncope, chest pain, or dizziness. CPX was stopped for fatigue in 53% of patients, leg fatigue in 23%, dyspnea in 21%, and miscellaneous reasons in 3%. CONCLUSIONS: This study suggests that CPX can be performed safely in pediatric patients with PH, with the exception of patients with severe limitation who were excluded from exercise testing. Although the number of patients in the sample is small, the data imply that the absence of significant patient symptoms and low incidence of arrhythmia or significant ST-segment depression make CPX a safe choice for measuring functional capacity in this patient population.

Desjardins F, Sekkali B, Verreth W, Pelat M, De Keyzer D, Mertens A, Smith G, Herregods MC, Holvoet P, Balligand JL. · Unit of Pharmacology and Therapeutics, Université catholique de Louvain, Belgium. · Eur Heart J. · Pubmed #18063594 links to  free full text

Abstract: AIMS: Statins improve atherosclerotic diseases through cholesterol-reducing effects. Whether the latter exclusively mediate similar benefits, e.g. on hypertension, in the metabolic syndrome is unclear. We examined the effects of rosuvastatin on the components of this syndrome, as reproduced in mice doubly deficient in LDL receptors and leptin (DKO). METHODS AND RESULTS: DKO received rosuvastatin (10 mg/kg/day or 20 mg/kg/day) or saline for 12 weeks. Saline-treated DKO mice had elevated blood pressure (BP) and nitric oxide-sensitive BP variability recorded by telemetry. Compared with saline, rosuvastatin (20 mg/kg/day) had no effect on weight gain and a minor effect on plasma cholesterol. Despite incomplete correction of insulin sensitivity, rosuvastatin fully corrected BP and its variability (P = 0.01), in conjunction with upregulation of PPARgamma (but not PPARalpha) in the aortic arch. Rosuvastatin similarly increased PPARgamma (P = 0.002) and SOD1 (P = 0.01) expression in isolated endothelial cells. Both GW9662, a PPARgamma-specific antagonist, and siRNA raised against PPARgamma abrogated rosuvastatin's effect, which was reproduced in PPARgamma- (but not PPARalpha-) dependent transactivation assays. CONCLUSION: Beyond partial improvement in insulin sensitivity, rosuvastatin normalized BP homeostasis in obese dyslipidaemic mice independently of changes in body weight or plasma cholesterol. Upregulation of PPARgamma and SOD1 in the endothelium may be involved as a unique vasculoprotective effect of statin treatment.

MacDonald SE, Walker M, Ramshaw H, Godwin M, Chen XK, Smith G. · Queen's University, Kingston, ON. · J Obstet Gynaecol Can. · Pubmed #17825134 No free full text.

Abstract: OBJECTIVES: The objective of this study was to ascertain the knowledge base of Ontario maternity care providers (family physicians, obstetrician-gynaecologists, and midwives) regarding the future health risks of gestational hypertension and preeclampsia and the practices with respect to communication of these risks. METHODS: In 2004, all obstetricians (639) and midwives (249) in Ontario and a random sample of 600 Ontario family physicians were mailed a survey and a reminder. Non-responders were also sent a second, and in some cases, a third copy of the survey. The survey addressed areas of knowledge, reported practices, and both patient and interprofessional communication. Descriptive analysis was used for the responses. RESULTS: The overall response rate was 42%. The majority of respondents were familiar with the long-term risks of gestational hypertension and preeclampsia. Although maternity care providers stated that they inform women with these conditions about their subsequent risks and recommend follow-up, only 36% usually inform the women's primary care providers about that subsequent risk. Only 58% of family physicians reported that they are usually informed by the maternity care providers about their patients who developed hypertension in pregnancy, compared with the 83% of maternity care providers who reported that they usually communicate this information to family physicians. CONCLUSION: We have identified weaknesses in knowledge base and communication amongst Ontario maternity care providers that suggest that the identification and follow-up of women with hypertensive disorders of pregnancy is not occurring. These deficiencies would be amenable to directed educational activities, including reviews, presentations, and the development and implementation of guidelines.

Strand A, Kjeldsen SE, Gudmundsdottir H, Os I, Smith G, Bjørnerheim R. · Department of Cardiology, Ullevaal University Hospital, Oslo, Norway. · Eur J Echocardiogr. · Pubmed #17448731 links to  free full text

Abstract: AIMS: Hypertension is one of several risk factors of cardiovascular disease and is associated with left ventricular (LV) systolic and diastolic dysfunction. A method for reliably detecting the onset of LV dysfunction before transition to irreversible damage of the myocardium would be of crucial importance in subjects with essential hypertension. METHODS AND RESULTS: Subjects with clear differences in BP level, development and duration of the hypertensive disease were examined at the age of 60 yrs: normotensives (n = 17), new hypertensives who developed hypertension over a 20 year period (n = 15) and hypertensives (n = 19). Relationships between conventional echocardiographic and tissue velocities imaging (TVI) parameters compared to LV parameters, and TVI as an estimate of LV function were explored. E'(Lat) (TVI peak early diastolic velocity) (P = 0.006) and E/E'(Lat) (P = 0.002) demonstrated differences in diastolic function between the groups. There were no significant differences regarding systolic myocardial velocities. E'(Lat) correlated to S'(Lat) (TDI peak systolic velocity) (r = 0.32, P = 0.026) and was independently predicted by S'(Lat) (R(2) = 0.24, P = 0.025) in multivariate analysis. E'(Lat) correlated negatively to LV mass index (r = -0.34, P = 0.012), also in multivariate regression analysis (R(2) = 0.12, P = 0.032). CONCLUSIONS: Myocardial diastolic velocities and mitral flow to annulus velocity ratio differentiated LV function between the hypertensive and normotensive groups. The parameters probably reflect changes in relaxation, recoil and contraction and parallel changes in LV mass index.

Chen XK, Wen SW, Smith G, Yang Q, Walker M. · OMNI Research Group, Clinical Epidemiology Program, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada. · BJOG. · Pubmed #17233856 No free full text.

Abstract: OBJECTIVE: To assess the effect of pregnancy-induced hypertension (PIH) on infant mortality in different birthweight centiles (small for gestational age [SGA], appropriate for gestational age [AGA], and large for gestational age [LGA]) and gestational ages (early preterm, late preterm, and full term). DESIGN: Retrospective cohort study. SETTING: Linked birth and infant death data set of USA between 1995 and 2000. POPULATION: A total of 17 464 560 eligible liveborn singleton births delivered after 20th gestational week. METHODS: Multivariate logistic regression models were applied to evaluate the association between PIH and infant mortality, with adjustment of potential confounders stratified by birthweight centiles and gestational age. MAIN OUTCOME MEASURE: Infant death (0-364 days) and its three components: early neonatal death (0-6 days), late neonatal death (7-27 days), and postneonatal death (28-364 days). RESULTS: PIH was associated with decreased risks of infant mortality, early neonatal mortality, and late neonatal mortality in both preterm and term SGA births, and PIH was associated with lower postneonatal mortality in preterm SGA births. PIH was associated with decreased risks of infant mortality, early neonatal mortality, late neonatal mortality and postneonatal mortality in preterm AGA births. Decreased risk of infant mortality and early neonatal mortality was associated with PIH in early preterm LGA births. CONCLUSIONS: The association between PIH and infant mortality varies depending on different birthweight centiles, gestational age, and age at death. PIH is associated with a decreased risk of infant mortality in SGA births, preterm AGA births, and early preterm LGA births.

Chen XK, Wen SW, Smith G, Leader A, Sutandar M, Yang Q, Walker M. · OMNI Research Group, Department of Obstetrics & Gynecology, University of Ottawa, Ottawa, Ontario, Canada. · Hypertens Pregnancy. · Pubmed #17065042 No free full text.

Abstract: OBJECTIVE: To examine the association between maternal age, paternal age, and new-onset hypertension in late pregnancy. METHODS: We carried out a retrospective cohort study of 9,302,675 pregnant women with live births in the United States between 1995 and 1998. Maternal and paternal ages were analyzed together using "couple age" in multivariate logistic regression models to reduce colinearity between maternal age and paternal age. The effect of paternal age was also analyzed with stratification of maternal age. RESULTS: Compared with couples with both a maternal and paternal age of 20 to 34 years, an older maternal age (above 35 years) was associated with an increased risk for new-onset hypertension, except for couples with a very young father (below 20 years). Younger maternal age (below 20 years) was associated with a decreased risk for new-onset hypertension, except for couples with a very old father (above 45 years). There was no significant association between paternal age and new-onset hypertension with stratification of maternal age. CONCLUSION: Increased risk for new-onset hypertension in late pregnancy is significantly associated with advancing maternal age, whereas there is no association between paternal age and new-onset hypertension in late pregnancy.

Chen XK, Wen SW, Smith G, Yang Q, Walker M. · OMNI Research Group, Department of Obstetrics & Gynecology, University of Ottawa, Ottawa, Ontario, Canada. · Hypertens Pregnancy. · Pubmed #17065041 No free full text.

Abstract: OBJECTIVE: To assess the association between new-onset hypertension in late pregnancy (NOH) and fetal and infant mortality in early preterm, late preterm, and full-term twins. METHODS: We conducted a retrospective cohort study in 275, 316 twins in 1995-1997 based on multiple birth registration dataset of USA. Generalized estimating equations (GEEs) was used to evaluate the odds ratios (OR) of fetal and infant death (at individual level) associated with NOH, with adjustment of potential confounders at both twin set level and individual level. RESULTS: The risks for early neonatal death (OR = 0.52, 95% CI: 0.36, 0.76) and late neonatal death (OR = 0.57, 95% CI: 0.37, 0.87) were decreased in early preterm twins born to mothers with NOH compared with early preterm twins born to mothers with normal blood pressure. The decreased risks for fetal death (OR = 0.40, 95% CI: 0.30, 0.53; OR = 0.46, 95% CI: 0.53, 0.65) and infant death (OR = 0.35, 95% CI: 0.28, 0.44; OR = 0.68, 95% CI: 0.51, 0.91) were associated with NOH in both early and late preterm twins, whereas no association between NOH and fetal/infant mortality were observed in full-term twins. CONCLUSION: NOH is associated with lower risk of fetal death and infant death in preterm twins.

Strand AH, Gudmundsdottir H, Os I, Smith G, Westheim AS, Bjørnerheim R, Kjeldsen SE. · Department of Cardiology, Ullevaal University Hospital, Oslo, Norway. · J Hypertens. · Pubmed #16612253 No free full text.

Abstract: BACKGROUND: Increased sympathetic activity may be an underlying mechanism in cardiovascular disease. It has been hypothesized that the degree of left ventricular (LV) hypertrophy is partly related to the blood pressure level, and partly to neurohormonal factors. The aim of this study was to investigate predictors of LV mass, including arterial plasma noradrenaline as an index of sympathetic activity, with particular emphasis on subjects who developed hypertension over a period of 20 years. METHODS: In a 20-year prospective study of middle-aged men, sustained hypertensives (n = 22), new hypertensives (crossovers) (n = 17) and sustained normotensives (controls) (n = 17) were examined both at baseline and after 20 years of follow-up (at ages 42.1 +/- 0.5 and 62.3 +/- 0.6 years, respectively). Relationships between arterial plasma catecholamines, blood pressure and body mass index at baseline to left ventricular parameters by echocardiography at follow-up were investigated. RESULTS: Groups were homogeneous regarding age, gender, race and body build. The group of sustained hypertensives had significantly more LV hypertrophy (P = 0.025) and diastolic dysfunction (P = 0.010). Among the crossovers, LV mass index was positively correlated to arterial plasma noradrenaline (r = 0.50, P = 0.043) and body mass index (BMI) (r = 0.51, P = 0.039) and showed a positive trend with systolic blood pressure (SBP) at baseline. Arterial plasma noradrenaline (beta = 0.47) was found to predict LV mass index after 20 years independently of BMI (beta = 0.45) and SBP (beta = 0.22) at baseline (R adjusted = 0.345, P = 0.037). Such a relationship was not found in the controls or in the sustained hypertensives, of which 16 were treated with antihypertensive drugs. CONCLUSIONS: Arterial plasma noradrenaline at baseline, as an index of sympathetic activity, predicts LV mass at follow-up independently of systolic blood pressure and body build in middle-aged men who developed hypertension over a period of 20 years.

Chen XK, Wen SW, Smith G, Yang Q, Walker M. · OMNI Research Group, Department of Obstetrics & Gynecology, University of Ottawa, Ottawa, Ontario, Canada. · BJOG. · Pubmed #16579801 No free full text.

Abstract: OBJECTIVE: To assess the association between pregnancy-induced hypertension (PIH) and infant mortality. DESIGN: Retrospective cohort study. SETTING: Birth and infant death registration dataset of the USA. POPULATION: A total of 17,432,987 eligible, liveborn singleton births in 1995-2000. METHODS: Multivariate logistic regression was applied to evaluate the association between PIH and infant mortality, with adjustment of potential confounders. MAIN OUTCOME MEASURES: Infant death (0-364 days) and its three components: early neonatal death (0-6 days), late neonatal death (7-27 days), and postneonatal death (28-364 days). RESULTS: There was a significant reduction in infant mortality associated with PIH in early preterm infants (OR = 0.59, 95% CI: 0.56-0.63) and in late preterm infants (OR = 0.80, 95% CI: 0.73-0.87), but a significant increase in term infants (OR = 1.08, 95% CI: 1.02-1.14). Both in early preterm and late preterm births, early neonatal mortality (OR = 0.38, 95% CI: 0.34-0.42; OR = 0.68, 95% CI: 0.61-0.77) and late neonatal mortality (OR = 0.59, 95% CI: 0.50-0.70; OR = 0.76, 95% CI: 0.61-0.96) were decreased in infants born to mothers with PIH compared with those born to mothers with normal blood pressure. The PIH-associated reduction in neonatal mortality among preterm singletons was stronger in small-for-gestational-age infants than in normal growth infants and stronger in infants born to nulliparous women than in those born to multiparous women. CONCLUSIONS: PIH is associated with lower risk of infant death in preterm births but higher risk in term births.

Olsen MH, Wachtell K, Bella JN, Palmieri V, Gerdts E, Smith G, Nieminen MS, Dahlöf B, Ibsen H, Devereux RB. · Department of Internal Medicine, Glostrup University Hospital, Glostrup, Denmark. · Am J Hypertens. · Pubmed #16280277 No free full text.

Abstract: BACKGROUND: Aortic valve (AV) sclerosis and urine albumin/creatinine ratio (UACR) are both markers of atherosclerosis. We aimed to investigate whether they predicted cardiovascular (CV) events independently in patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy. METHODS: After 2 weeks of placebo treatment, clinical, laboratory, and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy who had electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured calculating UACR. The presence of AV sclerosis was defined as valve thickening or calcification. Fifteen patients with mild AV stenosis were excluded. The patients were followed for 60 +/- 4 months and the composite endpoint (CEP) of CV death, nonfatal stroke, or nonfatal myocardial infarction was recorded. RESULTS: A value of UACR above the median value of 1.406 was associated with higher incidence of CEP and CV death in patients with AV sclerosis (CEP: 18.8% v 9.0% P < 0.05, CV death: 7.1% v 0.7% P < 0.01) and in patients without AV sclerosis (CEP: 14.0% v 4.9% P < 0.001, CV death: 5.1% v 1.1% P < 0.01). In Cox regression analysis, AV sclerosis predicted CEP (hazard ratio [HR] = 1.52, P < .05), but not CV death (HR = 1.30 [0.62 to 2.70], NS) independently of logUACR (HR = 1.70 and HR = 3.25, both P < .001). After adjusting for the Framingham Risk Score, CV disease, diabetes, smoking, and treatment allocation, AV sclerosis predicted CEP (HR = 1.5, P < .05) but not CV death (HR = 1.4, NS) independently of logUACR (HR = 1.2, P = .09 and HR = 1.94, P < .05). CONCLUSIONS: In hypertensive patients with electrocardiographic LV hypertrophy, AV sclerosis predicted CEP but not CV death independently of UACR after adjusting for CV risk factors and treatment allocation, indicating that AV sclerosis and UACR might be markers of different aspects of the atherosclerotic process.

Chen XK, Yang Q, Smith G, Krewski D, Walker M, Wen SW. · OMNI Research Group, Department of Obstetrics & Gynecology, University of Ottawa, Ottawa, ON, Canada. · Environ Res. · Pubmed #16131463 No free full text.

Abstract: Previous studies have suggested that environmental lead exposure increases the risk of hypertension in the general population. In this article, the authors used the 1998 linked birth/infant death database of the United States to examine the association between environmental lead level and the occurrence of pregnancy-induced hypertension (PIH). Yearly summaries of environmental lead levels were abstracted from the US Environmental Protection Agency's air pollution databases, and linked with birth/infant death records by state codes. Generalized estimating equations (GEEs) were used to evaluate the odds ratios of PIH associated with environmental lead measured at ecological levels, with adjustment for maternal age, race, education level, marital status, parity, and adequacy of prenatal care measured at individual levels, stratified by maternal cigarette smoking. A total of 2,994,072 women pregnant in 1998 were included in this study. With the first quartile of lead level as the reference group, the odds ratio for PIH among all study subjects in the second quartile of seasonal average lead level at conception was 1.07 (95% CI: 1.05-1.08), and odds ratios in the third and fourth quartiles were 1.22 (95% CI: 1.20-1.25) and 1.16 (95% CI: 1.15-1.18), respectively. The odds ratios for the second, third, and fourth quartiles of seasonal average lead level at birth were 1.07 (95% CI: 1.05-1.09), 1.21 (95% CI: 1.19-1.23), and 1.15 (95% CI: 1.13-1.17), respectively. The risk of PIH increased by 4% per 0.05 microg/m3 increase in seasonal average lead level at conception and birth, in both smokers and nonsmokers. These results suggest that higher environmental lead levels increase the risk of PIH.

Olsen MH, Wachtell K, Bella JN, Gerdts E, Palmieri V, Nieminen MS, Smith G, Ibsen H, Devereux RB, Anonymous00133. · Department of Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, DK-2600 Glostrup, Denmark. <> · Am J Cardiol. · Pubmed #15619412 No free full text.

Abstract: This study investigated whether aortic valve (AV) sclerosis was associated with traditional cardiovascular (CV) risk factors and CV events in hypertensive patients with electrocardiographic left ventricular (LV) hypertrophy, as previously demonstrated in the general population. AV sclerosis was associated with several CV risk factors and predicted CV events independently of prevalent CV disease and traditional CV risk factors, including LV mass and ejection fraction.

Wachtell K, Papademetriou V, Smith G, Gerdts E, Dahlöf B, Engblom E, Aurigemma GP, Bella JN, Ibsen H, Rokkedal J, Devereux RB. · Department of Medicine, Copenhagen County University Hospital, Glostrup, Denmark. · Am Heart J. · Pubmed #15389245 No free full text.

Abstract: BACKGROUND: Patients with hypertensive left ventricular (LV) hypertrophy commonly have diastolic dysfunction with preserved LV ejection fraction. LV systolic midwall shortening (MWS) may be impaired in hypertensive patients with normal LV ejection fraction. However, it is unclear whether impaired LV filling is related to depressed systolic midwall mechanics. METHODS: Echocardiographic measures of LV diastolic filling and systolic performance were compared in 632 unmedicated patients with stage II or III hypertension and LV hypertrophy determined by electrocardiogram, with LV ejection fraction >55% and <2+ mitral regurgitation. RESULTS: Stress-corrected LV MWS, an index of myocardial contractility, was lower in patients with abnormal as opposed to normal LV filling patterns (98% +/- 12% vs 102% +/- 10%, P <.001) and in patients with prolonged as opposed to normal isovolumic relaxation time (IVRT) (98% +/- 13% vs 101% +/- 12%, P =.014). Stress-corrected MWS was <85% of predicted levels in more patients with abnormal LV filling patterns (11.8% vs 6.3%) or with long IVRT (> or =105 msec) (34% vs 21%, both P <.05). In regression analyses, lower stress-corrected MWS and higher LV mass were independent correlates of longer IVRT, while lower stress-corrected MWS was the only independent correlate of prolonged mitral valve deceleration time (P =.017). Higher LV mass had strong, statistically independent relationships to longer IVRT (by 0.3 g/msec) and decreased stress-corrected MWS (by 0.5 g/%; both P <.0001), independent of body size and age. CONCLUSION: In patients with moderate hypertension and target organ damage who have normal LV ejection fraction, impaired early diastolic LV relaxation (abnormal E/A ratio, prolonged IVRT and deceleration time) is associated with impaired LV systolic midwall mechanics independent of higher LV mass.

Olsen MH, Wachtell K, Bella JN, Palmieri V, Gerdts E, Smith G, Nieminen MS, Dahlöf B, Ibsen H, Devereux RB. · Department of Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, Glostrup, Denmark. · J Hum Hypertens. · Pubmed #15085167 No free full text.

Abstract: We wanted to investigate whether urine albumin/creatinine ratio (UACR) and left ventricular (LV) mass, both being associated with diabetes and increased blood pressure, predicted cardiovascular events in patients with hypertension independently. After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy with electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured to calculate UACR. The patients were followed for 60+/-4 months and the composite end point (CEP) of cardiovascular (CV) death, nonfatal stroke or nonfatal myocardial infarction was recorded. The incidence of CEP increased with increasing LV mass (below the lower quartile of 194 g to above the upper quartile of 263 g) in patients with UACR below (6.7, 5.0, 9.1%) and above the median value of 1.406 mg/mmol (9.7, 17.0, 19.0%(***)). Also the incidence of CV death increased with LV mass in patients with UACR below (0, 1.4, 1.3%) and above 1.406 mg/mmol (2.2, 6.4, 8.0%(**)). The incidence of CEP was predicted by logUACR (hazard ratio (HR)=1.44(**) for every 10-fold increase in UACR) after adjustment for Framingham risk score (HR=1.05(***)), history of peripheral vascular disease (HR=2.3(*)) and cerebrovascular disease (HR=2.1(*)). LV mass did not enter the model. LogUACR predicted CV death (HR=2.4(**)) independently of LV mass (HR=1.01(*) per gram) after adjustment for Framingham risk score (HR=1.05(*)), history of diabetes mellitus (HR=2.4(*)) and cerebrovascular disease (HR=3.2(*)). (*)P<0.05, (**)P<0.01, (***)P<0.001. In conclusion, UACR predicted CEP and CV death independently of LV mass. CV death was predicted by UACR and LV mass in an additive manner after adjustment for Framingham risk score and history of CV disease.

Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, Ordin DL, Krumholz HM. · Denver Health Medical Center, Division of Cardiology, Colorado 80204, USA. · J Am Coll Cardiol. · Pubmed #12535812 No free full text.

Abstract: OBJECTIVES: This study was designed to determine if women are more likely than men to have heart failure (HF) with preserved systolic function after adjustment for potential confounders, including age. BACKGROUND: Although prior evidence suggests an independent association between female gender and preserved left ventricular systolic function (LVSF) in patients with HF, existing studies are limited by referral biases, small sample sizes, or the inability to adjust for a wide range of potential confounding variables. METHODS: This is a cross-sectional study using data from retrospective medical chart abstraction of a national sample of Medicare beneficiaries hospitalized with the principal discharge diagnosis of HF in acute-care nongovernmental hospitals in the U.S. between April 1998 and March 1999. Patients were eligible for this analysis if they were age 65 years or older, had documentation of LVSF, and corroboration of the diagnosis of HF. We used multivariable logistic regression to identify the correlates of preserved LVSF, which was defined as qualitatively normal function or quantitatively reported ejection fraction > or =0.50. Stratified regressions by gender were performed to identify significant interactions. RESULTS: Of the 19,710 patients in the analysis, preserved LVSF was present in 6,700 (35%), 79% of whom were women. In contrast, among the 12,956 patients with impaired LVSF, only 49% were women. Patients with preserved LVSF were 1.5 years older than those with impaired LVSF. After adjustment for age and other patient factors, female gender remained strongly associated with preserved LVSF (calculated risk ratio = 1.71; 95% confidence interval 1.63 to 1.78). The association was consistent in all age groups, and was similar in patients with or without coronary artery disease, hypertension, pulmonary disease, renal insufficiency, or atrial fibrillation. CONCLUSIONS: In elderly patients hospitalized with HF, preserved systolic function is primarily a condition of women, independent of important demographic and clinical characteristics.

Singh SJ, Smith G. · Department of Paediatric Urology, New Children's Hospital, Westmead, Sydney, NSW, Australia. · Pediatr Surg Int. · Pubmed #11666051 No free full text.

Abstract: Endoscopic incision of a ureterocele (EIU) is simple when compared to an open procedure such as ureterocele excision with or without an upper-pole nephrectomy. It has, however, the potential to induce vesicoureteric reflux (VUR), which traditionally requires further surgical intervention. The natural history of the VUR that develops following EIU is not known. We have treated asymptomatic VUR that developed following EIU conservatively and have surgically intervened only in cases with recurrent urinary tract infections (UTI). This is a review from a single surgeon's practice involving 29 consecutive cases of ureterocele spread over a period of 4 years. The range of follow up was 4-54 months (median 32). Of the 24 children who underwent primary EIU, 6 required a second procedure, 3 a reincision and 3 an open procedure. Of the 3 who had a reincision, 2 required a further open procedure. The indication for reincision was failure of decompression of the upper tract and the indication for an open procedure was recurrent UTI following EIU. Thus, overall success was achieved in 19 of 24 cases of primary EIU (79.2%). VUR following EIU appeared in 10 cases (41%); UTI developed in only 5 (50%) of these 10 cases. Overall, UTI developed in 6 of the 24 (25%) cases of primary EIU. Eight children had an open procedure (3 as a primary procedure and 5 after EIU); 2 (25%) from this group had UTI following the procedure, and interestingly, neither had VUR. Ureterocele incision is thus a good alternative to upper-pole nephrectomy or excision of the ureterocele, especially in infancy. There is an inherent risk of producing VUR in the postincision period, however, the majority of cases can be managed conservatively. All patients need to be monitored for hypertension and UTI following EIU.

Devereux RB, Bella J, Boman K, Gerdts E, Nieminen MS, Rokkedal J, Papademetriou V, Wachtell K, Wright J, Paranicas M, Okin PM, Roman MJ, Smith G, Dahlöf B. · Department of Medicine, The New York Hospital-Cornell Medical Center, NY, USA. · Blood Press. · Pubmed #11467763 No free full text.

Abstract: AIM: To assess the prevalence of echocardiographic left ventricular hypertrophy (LVH) and concentric remodeling in hypertensive patients with electrocardiographic (ECG)-LVH and to estimate the cost-effectiveness of echocardiography and ECG for detection of LVH. DESIGN: Echocardiographic LV measurements and the prevalence of abnormal LV geometric patterns were compared between 964 hypertensive patients with ECG-LVH (Cornell voltage-duration product > 2440 and/or SV1 +/- RV5-6 > 38 mm) participating in the LIFE trial and groups of 282 employed hypertensives and 366 apparently normal adults. RESULTS: Among both women and men, stepwise increases from reference subjects to employed hypertensives to LIFE patients were observed for LV wall thicknesses, chamber size and mass. Mean LV mass/body surface area (BSA) and LV mass/height(2.7) were substantially larger in LIFE patients than normal adults among women (113 vs 69 g/m2 and 55 vs 32 g/m(2.7), p <0.001) and men (127 vs 83 g/m2 and 55 vs 36 g/m(2.7), p < 0.001), with intermediate values in employed hypertensives. Compared to the latter group, LIFE patients had higher prevalences of concentric LVH (25-29% vs 3-4%) and eccentric LVH (45-51% vs 13-17%) but not concentric LV remodeling (8-11% vs 12-14%). LVH was present in 70% of LIFE patients by LV mass/BSA criteria and 76% by LV mass/height(2.7) criteria (odds ratios = 11.4 and 13.5 vs employed hypertensives). CONCLUSIONS: The ECG criteria used in LIFE identify hypertensive patients with a >70% prevalence of anatomic LVH, allowing accurate identification of high-risk status by this commonly used technique.