Exercise Training Restores Baroreflex Sensitivity

Exercise Training Restores Baroreflex Sensitivity in Never-Treated Hypertensive Patients

Mateus C. Laterza; Luciana D.N.J. de Matos; Ivani C. Trombetta; Ana M.W. Braga; Fabiana Roveda; Maria J.N.N. Alves; Eduardo M. Krieger; Carlos E. Negrão; Maria U.P.B. Rondon
From the Heart Institute (InCor) (M.C.L., L.D.N.J.d.M., I.C.T., A.M.W.B., F.R., M.J.N.N.A., E.M.K., C.E.N., M.U.P.B.R.), University of São Paulo Medical School, São Paulo, Brazil; and the School of Physical Education and Sports (C.E.N.), University of São Paulo, São Paulo, Brazil

The effects of exercise training on baroreflex control of sympathetic nerve activity in human hypertension are unknown.
We hypothesized that exercise training would improve baroreflex control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in patients with hypertension and that exercise training would reduce MSNA and blood pressure (BP) in hypertensive patients. Twenty never-treated hypertensive patients were randomly divided into 2 groups: exercise-trained (n=11; age: 46±2 years) and untrained (n=9; age: 42±2 years) patients. An age-matched normotensive exercise-trained group (n=12; age: 42±2 years) was also studied.
Baroreflex control of MSNA (microneurography) and HR (ECG) was assessed by stepwise intravenous infusions of phenylephrine and sodium nitroprusside and analyzed by linear regression. BP was monitored on a beat-to-beat basis. Exercise training consisted of three 60-minute exercise sessions per week for 4 months. Under baseline conditions (before training), BP and MSNA were similar between hypertensive groups but significantly increased when compared with the normotensive group.
Baroreflex control of MSNA and HR was similar between hypertensive groups but significantly decreased when compared with the normotensive group.
In hypertensive patients, exercise training significantly reduced BP (P<0.01) and MSNA (P<0.01) levels and significantly increased baroreflex control of MSNA and HR during increases (P<0.01 and P<0.03, respectively) and decreases (P<0.01 and P<0.03, respectively) in BP.
The baseline (preintervention) difference in baroreflex sensitivity between hypertensive patients and normotensive individuals was no longer observed after exercise training. No significant changes were found in untrained hypertensive patients.
In conclusion, exercise training restores the baroreflex control of MSNA and HR in hypertensive patients. In addition, exercise training normalizes MSNA and decreases BP levels in these patients.

Keywords: hypertension • baroreflex sensitivity • sympathetic nerve activity • exercise • blood pressure

Hypertension, June, 2007,Vol.49, №6; p.1298.
© 2007 American Heart Association, Inc.

Pulse Pressure: Cardiovascular events

Predictive Utility of Pulse Pressure and Other Blood Pressure Measures for Cardiovascular Outcomes

William J. Mosley, II; Philip Greenland; Daniel B. Garside; Donald M. Lloyd-Jones
From the Bluhm Cardiovascular Institute (D.M.L.-J., P.G.), the Department of Medicine (W.J.M., D.M.L.-J., P.G.), and the Department of Preventive Medicine (D.M.L-J., D.B.G., P.G.), Feinberg School of Medicine, Northwestern University, Chicago, Ill.

Data are sparse regarding the actual predictive utility of pulse pressure and other blood pressure measures for cardiovascular events.
We included all of the participants from the Chicago Heart Association Detection Project in Industry who were free of cardiovascular disease and not receiving antihypertensive treatment at baseline (1967–1973).
Baseline blood pressure measures were assessed for predictive utility for fatal and nonfatal events over 33 years. Among 36 314 participants (mean age: 39±13 years; 43.4% women), there were 11 452 deaths: 745 were attributed to stroke, 2812 to coronary disease, and 599 to heart failure. Of the 16 393 participants who attained Medicare eligibility, 3050, 1367, and 2207 had 1 hospitalization for stroke, myocardial infarction, or heart failure, respectively.
In univariate analyses, hazards ratios for stroke death per SD of pulse, systolic, and diastolic pressure, respectively, were 1.49, 1.75, and 1.71. Likelihood ratio 2 (134.3, 302.0, and 232.6, respectively), Bayes information criteria values (15 142, 14 974, and 15 044, respectively), and areas under receiver-operating characteristic curves (0.59, 0.64, and 0.63, respectively) all indicated better predictive utility for systolic and diastolic compared with pulse pressure.
Results for coronary or heart failure death and stroke, myocardial infarction, or heart failure hospitalization were similar.
Pulse pressure had weaker predictive utility at all ages but particularly for those <50 years.
In this large cohort study, pulse pressure had predictive utility for cardiovascular events that was inferior to systolic or diastolic pressure.
These findings support the approach of current guidelines in the use of systolic and diastolic blood pressure to assess risk and the need for treatment.

Keywords: hypertension • pulse pressure • stroke • coronary heart disease • heart failure • prediction

Hypertension, June, 2007,Vol.49, №6; p.1256.
© 2007 American Heart Association, Inc.

Childhood growth and Development of hypertension

Childhood Growth and Hypertension in Later Life

Johan G. Eriksson; Tom J. Forsén; Eero Kajantie; Clive Osmond; David J.P. Barker
From the National Public Health Institute (J.G.E., T.J.F., E.K.), Department of Health Promotion and Chronic Disease Prevention, Diabetes Unit, Helsinki, Finland; the Department of Public Health (J.G.E.), University of Helsinki, Helsinki, Finland; MRC Epidemiology Resource Centre (C.O.), University of Southampton, Southampton General Hospital, Southampton, United Kingdom; and the Heart Research Center (D.J.P.B.), Oregon Health and Sciences University, Portland, Ore.

Few studies have examined the effects of both prenatal and postnatal growth on hypertension. We report on hypertension in 2003 people aged 62 years who were randomly selected from the Helsinki birth cohort and examined in a clinic.
Their heights and weights had been recorded serially up to age 11 years. A total of 644 had already been diagnosed with hypertension. Compared with normotensive people, they were obese and insulin resistant.
At birth they were thin and short, and they gained weight slowly up to age 2 years; thereafter they grew rapidly so that at age 11 years their body size was around the average. The odds ratio associated with each kilogram of birthweight was 0.42 (95% CI: 0.32 to 0.56); with each 10 kg of current weight it was 1.85 (95% CI: 1.66 to 2.05).
The blood pressures of another 802 people were classified as hypertensive under current definitions. They were overweight and had an atherogenic lipid profile. At birth they were short, and after birth they grew slowly so that at age 11 years they were short and thin. The odds ratio associated with each kilogram of weight at age 2 years was 0.75 (95% CI: 0.68 to 0.84); with each 10 kg of current weight it was 1.42 (95% CI: 1.28 to 1.57).
We conclude that 2 different paths of childhood growth precede the development of hypertension. We suggest that they lead to hypertension through different biological mechanisms and may respond differently to medication.

Keywords: hypertension • kidney • fetal programming • early growth • renin angiotensin system

Hypertension, June, 2007,Vol.49, №6; p.1415.
© 2007 American Heart Association, Inc.

Sleep blood pressure and Mortality

Predictors of All-Cause Mortality in Clinical Ambulatory Monitoring

Unique Aspects of Blood Pressure During Sleep

Iddo Z. Ben-Dov; Jeremy D. Kark; Drori Ben-Ishay; Judith Mekler; Liora Ben-Arie; Michael Bursztyn

From the Nephrology and Hypertension (I.Z.B.-D.), Epidemiology Unit (J.D.K.), and Mount-Scopus Internal Medicine Department (D.B.-I., J.M., L.B.-A., M.B.), Hadassah–Hebrew University Medical Center, Jerusalem, Israel

The prognostic value of sleep blood pressure reported by recent studies is variable.
Our aim was to examine the relationship of sleep blood pressure, measured by 24-hour ambulatory blood pressure monitoring, with all-cause mortality.
We studied a cohort of 3957 patients aged 55±16 (58% treated) referred for ambulatory monitoring (1991–2005).
Sleep, including daytime sleep, was recorded by diary. Linkage with the national population register identified 303 deaths during 27 750 person-years of follow-up. Hazard ratios (HRs) for mortality in Cox proportional hazards models that included age, sex, hypertension, and diabetes treatment were 1.32 (95% CI: 0.99 to 1.76) for awake hypertension ( 135/85 mm Hg), and 1.67 (95% CI: 1.25 to 2.23) for sleep hypertension ( 120/70 mm Hg).
By quintile analysis, the upper fifths of systolic and diastolic dipping during sleep were associated with adjusted HRs of 0.58 (95% CI: 0.41 to 0.82) and 0.68 (95% CI: 0.48 to 0.96), respectively.
In a model controlling for awake systolic blood pressure, hazards associated with reduced systolic dipping increased from dippers (>10%; HR: 1.0), through nondippers (0% to 9.9%; HR: 1.30; 95% CI: 1.00 to 1.69) to risers (<0%;>
Thus, in practice, ambulatory blood pressure predicts mortality significantly better than clinic blood pressure.
The availability of blood pressure measures during sleep and, in particular, the pattern of dipping add clinically predictive information and provide further justification for the use of ambulatory monitoring in patient management.

Keywords: ambulatory blood pressure monitoring • dipping • mortality • cohort • sleep blood pressure

Hypertension, June, 2007,Vol.49, №6; p.1235.
© 2007 American Heart Association, Inc.

Blood Pressure and Ischemic Brain Injury

Association of Ambulatory Blood Pressure With Ischemic Brain Injury

Gary L. Schwartz; Kent R. Bailey; Thomas Mosley; David S. Knopman; Clifford R. Jack, Jr; Vincent J. Canzanello; Stephen T. Turner From the Division of Nephrology and Hypertension (G.L.S., S.T.T., V.J.C.), the Department of Diagnostic Radiology (C.R.J.), the Department of Neurology (D.S.K.), and the Department of Health Sciences Research (K.R.B.), Mayo Clinic College of Medicine, Rochester, Minn; and the Department of Geriatric Medicine (T.M.), University of Mississippi, Jackson

Cerebral white matter hyperintensities on brain MRI (leukoaraiosis) are associated with increased risk of stroke and dementia.
To assess the relationships of blood pressure level and circadian pattern with leukoaraiosis, we obtained 24-hour ambulatory blood pressure recordings and brain magnetic resonance images in 343 white and 267 black adults who were members of sibships that had 2 siblings with essential hypertension.
In multiple linear regression models, factors associated with greater leukoaraiosis in both racial groups included age (P 0.002), homocysteine levels (P 0.006), and brain volume (P 0.008).
In blacks, ambulatory blood pressure measures associated with greater leukoaraiosis were higher awake, asleep, and 24-hour systolic and diastolic levels (P 0.009 for each).
In addition, there was a trend for smaller nocturnal declines in systolic and diastolic levels (ie, nondipping patterns) to be associated with greater leukoaraiosis, and all of these associations, except nondipping of diastolic level, remained or became significant after controlling for office blood pressure (P<0.05>
However, similar to findings in blacks, nondipping of systolic and diastolic ambulatory blood pressure levels were each associated with greater leukoaraiosis (P 0.008), and all of these associations remained or became significant after controlling for office blood pressure (P 0.009 for each).
Higher ambulatory blood pressure levels and a nondipping circadian pattern contribute to greater leukoaraiosis volume after controlling for office blood pressure.

Keywords: ambulatory blood pressure • leukoaraiosis • predictors • hypertension • target organ injury

Hypertension, June, 2007,Vol.49, №6; p.1228.
© 2007 American Heart Association, Inc.

Blood Pressure and Sleep

On the Physiology of Blood Pressure Decrease During Nocturnal Sleep in Healthy Humans

Friedhelm Sayk; Christoph Becker; Christina Teckentrup; Horst-Lorenz Fehm; Jan Struck; Jens Peter Wellhoener; Christoph Dodt
From the Clinic for Internal Medicine I, University Hospital of Schleswig-Holstein, Luebeck, Germany

That sleep is accompanied by a blood pressure decrease is well known; however, the underlying physiology deserves further investigation.

The present study examines in healthy subjects 2 main questions: is this dipping actively evoked? and what are the consequences of nondipping for daytime blood pressure?

Nocturnal blood pressure was extrinsically elevated in 12 sleeping subjects to mean daytime values by continuously infused phenylephrine.

This nondipping significantly lowered morning blood pressure during rest and 3 hours after resuming physical activity compared with a control condition (isotonic saline).

Neither muscle sympathetic nerve activity nor sensitivity of -adrenoceptors was reduced. However, the set point for initiation of regulatory responses through the baroreflex was clearly shifted toward lower blood pressure levels.

Our results support the hypothesis of an actively regulated central mechanism for blood pressure resetting and set point consolidation of the baroreflex during nighttime sleep.

This is suggested by the fact that extrinsically induced nondipping induces sustained decrease in blood pressure during the following morning through an actively lowered baroreflex set point.

Keywords: dipping • baroreflex • microneurography • MSNA • sympathovagal balance

Hypertension. 2007;49:1070.

© 2007 American Heart Association, Inc.

Mild and Moderate Hypertension: Cerebral Hemodynamics

Cerebral Hemodynamics After Short- and Long-Term Reduction in Blood Pressure in Mild and Moderate Hypertension

Rong Zhang; Sarah Witkowski; Qi Fu; Jurgen A.H.R. Claassen; Benjamin D. Levine
From the Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas and the University of Texas Southwestern Medical Center at Dallas

This study tested the hypothesis that acute reduction in blood pressure (BP) at the initial stage of antihypertensive therapy compromises brain perfusion and dynamic cerebral autoregulation in patients with hypertension.

Cerebral blood flow velocity and BP were measured in patients with mild and moderate hypertension and in healthy volunteers at baseline upon reduction of BP within 1 to 2 weeks of administration of losartan/hydrochlorothiazide and after 3 to 4 months of treatment.

The transfer function between beat-to-beat changes in BP and cerebral blood flow velocity was estimated to assess dynamic autoregulation.

After 1 to 2 weeks of treatment, BP was reduced in mild (143±7/88±4 versus 126±12/77±6 mm Hg) and moderate hypertension (163±11/101±9 versus 134±17/84±9 mm Hg; P<0.05).>

These reductions in BP were well maintained over the 3 to 4 month period. Cerebral blood flow velocity did not change, whereas cerebrovascular resistance index was reduced by 17% (P<0.05)>

Baseline transfer function gain at the low frequencies (0.07 to 0.20 Hz) was reduced in moderate hypertension, consistent with cerebral vasoconstriction and/or enhanced dynamic autoregulation.

However, this reduced transfer function gain was restored to the level of control subjects after reduction in BP.

These findings, contrary to our hypothesis, demonstrate that there is a rapid adaptation of the cerebral vasculature to protect the brain from hypoperfusion even at the initial stage of antihypertensive therapy in patients with mild and moderate hypertension.

Keywords: hemodynamics • brain • hypertension • cerebral blood flow • angiotensin AT1 receptor • transcranial Doppler

Hypertension. 2007;49:1149.

© 2007 American Heart Association, Inc

Children: Blood pressure and Microcirculation

Blood Pressure and Retinal Arteriolar Narrowing in Children

Paul Mitchell; Ning Cheung; Kristin de Haseth; Bronwen Taylor; Elena Rochtchina; F. M. Amirul Islam; Jie Jin Wang; Seang Mei Saw; Tien Y. Wong
From the Centre for Vision Research (P.M., B.T., E.R., J.J.W.), Department of Ophthalmology, University of Sydney, New South Wales, Australia; Centre for Eye Research Australia (N.C., K.d.H., F.M.A.I., J.J.W., T.Y.W.), University of Melbourne, Victoria, Australia; Royal Melbourne Hospital (N.C.), Victoria, Australia; Medical University Leiden (K.d.H.), Leiden, The Netherlands; and Singapore Eye Research Institute (S.M.S., T.Y.W.) and the Department of Community, Occupational and Family Medicine (S.M.S.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Retinal arteriolar narrowing is a known response of hypertension and independently predicts cardiovascular mortality in adults. Whether elevated blood pressure leads to retinal arteriolar narrowing in young children is unknown.

We examined the relationship of retinal vascular caliber and blood pressure levels in 2 population-based cohorts among children aged 6 to 8 years in Sydney, Australia (1572 children) and Singapore (380 children). Participants had digital retinal photographs and measurement of retinal arteriolar (or small artery) and venular (or small vein) caliber.

Children with higher quartiles of blood pressure had significantly narrower retinal arterioles than those with lower blood pressure (retinal arteriolar caliber 162.8, 161.0, 157.8, and 157.1 µm (P for trend<0.001), trend="0.0024">

After controlling for age, sex, race, body mass index, refraction, and birth parameters, each 10-mm Hg increase in systolic blood pressure was associated with narrowing of the retinal arterioles by 2.08 µm (95% confidence interval: 1.38 to 2.79; P<0.0001) p="0.016)">

These associations were consistent across age, sex, body mass index, and birth parameters.

Retinal venules were not affected by blood pressure.

We conclude that higher childhood blood pressure is associated with retinal arteriolar narrowing.

Our data provide evidence that the effects of elevated blood pressure may manifest early in life.

Keywords: retinal arteriolar narrowing • blood pressure • children • microcirculation • hypertension

Hypertension. 2007;49:1156.

© 2007 American Heart Association, Inc.

Pregnancy and Previous Hypertensive Disease

Previous Hypertensive Disease of Pregnancy Is Associated With Alterations of Markers of Insulin Resistance

Joël Girouard; Yves Giguère; Jean-Marie Moutquin; Jean-Claude Forest
From the CHUQ (J.G., Y.G., J-C.F.), Hôpital St-François d’Assise, Faculté de Médecine, Université Laval, Québec City, Québec, Canada; and Centre hospitalier universitaire de Sherbrooke (J-M.M.), Pavillon Fleurimont, Sherbrooke, Québec, Canada

Insulin resistance syndrome has been observed in women with hypertensive disease of pregnancy, but few studies evaluated the presence of the syndrome a few years after delivery.

The objective of this study was to evaluate the presence of insulin resistance and its metabolic alterations in these women compared with those who had a normal pregnancy.

We performed an observational study in 168 women with previous hypertensive disease of pregnancy and 168 control subjects with normal pregnancy contacted, on average, 7.8 years after their first delivery (mean age: 34.8 years).

Complete blood lipid profile, insulin, glucose, homocysteine, adipokins, and markers of inflammation were measured.

Also, an oral glucose tolerance test was performed in 146 case and 135 control subjects. Case subjects were more overweight compared with control subjects.

We found significantly lower high-density lipoprotein cholesterol and adiponectin levels and higher apolipoprotein (apo) apoB/apoA1 ratio, homocysteine, leptin, and insulin levels among case subjects compared with control subjects (P 0.004).

Also, case subjects were more insulin resistant in the basal state estimated by homeostasis assessment model 2, as well as in the nonbasal state as estimated by insulin sensitivity indices calculated from the oral glucose tolerance test.

Finally, in a multivariate regression model, leptin, apoB/apoA1 ratio, waist circumference, adiponectin, and free fatty acids explained 40% of homeostasis assessment model 2 variance.

Young women with previous hypertensive disease of pregnancy show signs of insulin resistance within the first decade after delivery.

These findings suggest that insulin resistance may be the link between hypertensive disease of pregnancy and increased cardiovascular risk later in life.

Keywords: hypertension • insulin resistance • obesity • preeclampsia • gestational hypertension • cardiovascular diseases • dyslipidemia

Hypertension. 2007;49:1056.

© 2007 American Heart Association, Inc.

Pressor Effect of Salt

What Initiates the Pressor Effect of Salt in Salt-Sensitive Humans?
Observations in Normotensive Blacks

Olga Schmidlin; Alex Forman Anthony Sebastian; R. Curtis Morris, Jr
From the Division of Nephrology, Department of Medicine, University of California San Francisco.

We tested the traditional hypothesis that an abnormally enhanced renal reclamation of dietary NaCl alone initiates its pressor effect ("salt sensitivity").

Under metabolically controlled conditions, we grouped 23 normotensive blacks as either salt-sensitive (SS) or salt-resistant (SR), depending on whether or not dietary NaCl loading did or did not increase mean arterial blood pressure (MAP) by 5 mm Hg.

We determined whether dietary NaCl loading induces greater increases in external Na+ balance, plasma volume, and cardiac output in SS, compared with any in SR subjects, and differential changes in systemic vascular resistance (SVR) that could account for the pressor differences between SS and SR subjects.

Using impedance cardiography, we measured cardiac output and SVR daily at 4-hour intervals throughout the last 3 days of a 7-day period of low NaCl intake (30 mmol per day) and throughout a subsequent 7-day period of NaCl loading (250 mmol per day).

In the 11 SS subjects, compared with the 12 SR subjects, NaCl loading induced no greater increases in Na+ balance, body weight, plasma volume, and cardiac output. Yet, from days 2 to 7 of NaCl loading, changes of MAP in SS diverged progressively from those in SR.

From days 2 to 4, progressive increases of MAP in SS subjects reflected importantly impaired decreases of SVR, as judged from "normal" decreases of SVR in SR subjects.

In SS and SR subjects combined, changes in both MAP and SVR on day 2 strongly predicted changes in MAP on day 7.

In many normotensive blacks, vascular dysfunction is critical to the initiation of a pressor response to dietary NaCl.

Keywords: blood pressure • sodium chloride • electrolyte balance • vascular resistance • cardiac output

Hypertension. 2007;49:1032.

© 2007 American Heart Association, Inc.