Lead to heart attack treatments

System to analyze beating heart stem cells could lead to heart attack treatments

New research at the University of Nottingham, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is paving the way for techniques that use stem cells to repair the damage caused by heart attacks.

The research, highlighted in the new issue of BBSRC Business, is looking at the process that turns a stem cell into a cardiomyocyte - the beating cell that makes up the heart. The Nottingham researchers are developing a new system to monitor cardiomyocytes in real time as they differentiate from stem cells into beating heart cells. The system uses electrophysiology to record the electrical properties in a cell and will be the first time it has been used to study cardiomyocyte cells in the UK.

The researchers hope that their research could provide more detailed information on the electrical activity of stem cell derived cardiomyocytes. In the longer term, this could facilitate their use in regenerating the damaged hearts of heart attack victims.

"Human embryonic stem cells promise unrivalled opportunities. However, they are difficult, time-consuming and expensive to grow in the lab", Dr Denning explains. "Our understanding of how to convert them into cardiomyocytes is poor. At the moment we only know how to produce a few million cardiomyocytes, but to treat just one heart attack patient, we may need one billion that all function in the correct way."

To help overcome the many challenges that stem cells bring, Dr Denning and his team plan to engineer a novel system for real-time analysis of cardiomyocytes during early development so their properties are better understood.

The team have already demonstrated that sufficient numbers of stem cell-derived cardiomyocytes can be produced for detailed analysis and they plan to use new 'electrophysiology' systems to record changes in the cells when cultured. Electrophysiology is the study of cells' electrical properties and this is the first time that the method has been used in the UK to study stem cell-cardiomyocyte biology.

"This research will enable rapid development of stem cell-derived cardiomyocytes as a tool for understanding the heart and its diseases," says Dr Denning. However, he cautions: "Before we can consider using stem cells to treat heart-attack patients there are many problems which will take many years to solve. We don't yet know how to deliver the cells to a patient's heart and prevent them being washed away so that they actually stay in the heart and both survive and function. It will take many years to overcome these challenges and put stem cell-derived cardiomyocytes into medical usage."

The researchers will also be monitoring how the cells respond to different pharmacological agents in order to improve drug-screening processes and reduce the need for animal testing.

"A key part of the project is to monitor the effects of different drugs on the cells. At present, only limited information is available on how they respond to pharmacological or gene modulating agents.

"Between 1990 and 2001, 8 different drugs were withdrawn from the market in the USA at an estimated cost of $8billion because they caused unexpected deaths in several hundred patients. Our aim is to reduce such occurrences by having better test methods to test the drugs before they reach the clinic.

"By studying the drugs' effects on the heart cells in the lab, this could reduce the need for animals in clinical trials."

Biotechnology and Biological Sciences Research Council
http://www.brightsurf.com/news/

Blood Pressure and Stroke Recurrence

Relationship Between Blood Pressure and Stroke Recurrence in Patients With Intracranial Arterial Stenosis

Tanya N. Turan, MD; George Cotsonis, MA; Michael J. Lynn, MS; Seemant Chaturvedi, MD; Marc Chimowitz, MB, ChB, for the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Trial Investigators

From Emory University, Atlanta, Ga (T.N.T., G.C., M.J.L., M.C.), and Wayne State University, Detroit, Mich (S.C.).

Background. Many clinicians allow blood pressure to run high in patients with intracranial stenosis to protect against hypoperfusion. We sought to determine whether higher blood pressure decreases the risk of stroke in these patients.

Methods and Results. Data on 567 patients in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial were analyzed. Time to ischemic stroke and stroke in the same territory of the stenotic vessel was compared in patients grouped by mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) during the study. Additional analyses were based on severity and location of stenosis. Ischemic stroke risk increased with increasing mean SBP and DBP on univariate analysis (P<0.0001, P<0.0001) and after adjustment for risk factors (P=0.0008, P<0.0001). Elevated mean SBP and DBP also resulted in increased risk of stroke in the territory in univariate (P=0.0065, P<0.0001) and adjusted (P=0.0002, P=0.0005) analyses. The increased risk of stroke with increasing SBP was driven largely by patients in the highest SBP group. Patients with moderate (<70%) stenosis had increased risk of stroke (P<0.0001, P=0.003) and stroke in the territory (P=0.0002, P=0.010) with increased SBP and DBP. Patients with severe (70%) stenosis had increased risk of stroke and stroke in the territory with elevated DBP (P=0.004, P=0.004).

Conclusions. In patients with intracranial stenosis, higher blood pressure is associated with increased (not decreased) risk of ischemic stroke and stroke in the territory of the stenotic vessel. These findings argue strongly against the common clinical practice of maintaining high blood pressure in patients with intracranial stenosis.

Circulation. 2007;115:2969-2975.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/

Neopterin - Prognostic Value

Long-Term Prognostic Value of Neopterin
A Novel Marker of Monocyte Activation in Patients With Acute Coronary Syndrome

Kausik K. Ray, MRCP, MD; David A. Morrow, MD, MPH; Marc S. Sabatine, MD, MPH; Amy Shui, MA; Nader Rifai, PhD; Christopher P. Cannon, MD; Eugene Braunwald, MD

From the Department of Public Health and Primary Care (K.K.R.), University of Cambridge, Cambridge, United Kingdom; TIMI Study Group (D.A.M., M.S.S., A.S., C.P.C., E.B.), Cardiovascular Division and the Department of Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, Mass; and Children’s Hospital (N.R.), Boston, Mass.

Background. Monocyte activation is believed to play an important role in the pathogenesis of acute coronary syndromes (ACS). Neopterin is a soluble marker of monocyte activation, and elevated levels are of prognostic value in patients with stable coronary artery disease.

Methods and Results. Neopterin levels were measured on average at 7 days (in 3946 patients) and at 4 months (in 3369 patients) after ACS in the PRavastatin Or atorVastatin Evaluation Infection Therapy–Thrombolysis In Myocardial Infarction (PROVE IT–TIMI 22) trial. We assessed the relationship between plasma neopterin levels and the risk of death and death or acute coronary events (nonfatal myocardial infarction or unstable angina) over 2 years. Seven days after an ACS event, neopterin levels 12.11 nmol/L (upper quartile, derived from a post hoc analysis) were associated with an increased risk of death and an increased risk of death or acute coronary events after adjustment for age, gender, history of diabetes mellitus, history of hypertension, history of smoking, type of ACS presentation, use of percutaneous coronary intervention for the index event, statin regimen, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hazard ratio, 1.86 [95% CI, 1.24 to 2.77], P=0.003; and hazard ratio, 1.33 [95% CI, 1.09 to 1.63] P=0.006, respectively). Neopterin levels 12.11 nmol/L at 4 months remained a predictor of death alone and of death or acute coronary events after multivariable adjustment that included adjustment for month 4 low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and statin regimen (hazard ratio, 2.39 [95% CI, 1.43 to 3.99], P=0.001; and hazard ratio, 1.60 [95% CI, 1.21 to 2.11], P=0.001). High-dose atorvastatin significantly attenuated the risk among subjects with neopterin levels 12.11 nmol/L at baseline (interaction P for death or acute coronary event, 0.018).
Conclusions. Increased monocyte activation detected by an elevated plasma neopterin level identifies patients at long-term risk of death or recurrent acute coronary events after ACS. Intensive statin therapy significantly attenuates the risk of recurrent events among patients with an elevated neopterin level.

Circulation. 2007;115:3071-3078.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/cgi/content/abstract/115/24/3071

Coronary artery calcification

Coronary Artery Calcification Progression Is Heritable

Andrea E. Cassidy-Bushrow, PhD, MPH; Lawrence F. Bielak, DDS, MPH; Patrick F. Sheedy, II, MD; Stephen T. Turner, MD; Iftikhar J. Kullo, MD; Xihong Lin, PhD; Patricia A. Peyser, PhD
From the Department of Epidemiology, University of Michigan, Ann Arbor (A.E.C.-B., L.F.B., P.A.P.); Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Mich (A.E.C.-B.); Department of Diagnostic Radiology (P.F.S.), Division of Hypertension, Department of Internal Medicine (S.T.T.), and Division of Cardiovascular Diseases (I.J.K.), Mayo Clinic and Foundation, Rochester, Minn; and Department of Biostatistics, Harvard University, Boston, Mass (X.L.).

Background. Coronary artery calcification (CAC), a marker of coronary artery atherosclerosis, can be measured accurately and noninvasively with the use of electron beam computed tomography. Serial measures of CAC quantify progression of calcified coronary artery plaque. Little is known about the role of genetic factors in progression of CAC quantity.

Methods and Results. We quantified the relative contributions of measured risk factors and unmeasured genes to CAC progression measured by 2 electron beam computed tomography examinations an average of 7.3 years apart in 877 asymptomatic white adults (46% men) from 625 families in a community-based sample. After adjustment for baseline risk factors and CAC quantity, the estimated heritability of CAC progression was 0.40 (P<0.001). Baseline risk factors and CAC quantity explained 64% of the variation in CAC progression. Thus, genetic factors explained 14% of the variation [(100–64)x(0.40)] in CAC progression. After adjustment for risk factors, the estimated genetic correlation (pleiotropy) between baseline CAC quantity and CAC progression was 0.80 and was significantly different than 0 (P<0.001) and 1 (P=0.037). The environmental correlation between baseline CAC quantity and CAC progression was 0.42 and was significantly different than 0 (P=0.006).

Conclusions. Evidence was found that many but not all genetic factors influencing baseline CAC quantity also influence CAC progression. The identification of common and unique genetic influences on these traits will provide important insights into the genetic architecture of coronary artery atherosclerosis.

Circulation. 2007;116:25-31.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/

Sudden death in young athletes

Trends in Sudden Cardiovascular Death in Young Competitive Athletes

After Implementation of a Preparticipation Screening Program

Domenico Corrado, MD, PhD; Cristina Basso, MD, PhD; Andrea Pavei, MD; Pierantonio Michieli, MD, PhD; Maurizio Schiavon, MD; Gaetano Thiene, MD

Context. A nationwide systematic preparticipation athletic screening was introduced in Italy in 1982. The impact of such a program on prevention of sudden cardiovascular death in the athlete remains to be determined.

Objective. To analyze trends in incidence rates and cardiovascular causes of sudden death in young competitive athletes in relation to preparticipation screening.

Design, Setting, and Participants. A population-based study of trends in sudden cardiovascular death in athletic and nonathletic populations aged 12 to 35 years in the Veneto region of Italy between 1979 and 2004. A parallel study examined trends in cardiovascular causes of disqualification from competitive sports in 42 386 athletes undergoing preparticipation screening at the Center for Sports Medicine in Padua (22 312 in the early screening period [1982-1992] and 20 074 in the late screening period [1993-2004]).

Main Outcome Measures. Incidence trends of total cardiovascular and cause-specific sudden death in screened athletes and unscreened nonathletes of the same age range over a 26-year period.

Results. During the study period, 55 sudden cardiovascular deaths occurred in screened athletes (1.9 deaths/100 000 person-years) and 265 sudden deaths in unscreened nonathletes (0.79 deaths/100 000 person-years). The annual incidence of sudden cardiovascular death in athletes decreased by 89% (from 3.6/100 000 person-years in 1979-1980 to 0.4/100 000 person-years in 2003-2004; P for trend < .001), whereas the incidence of sudden death among the unscreened nonathletic population did not change significantly. The mortality decline started after mandatory screening was implemented and persisted to the late screening period. Compared with the prescreening period (1979-1981), the relative risk of sudden cardiovascular death in athletes was 0.56 in the early screening period (95% CI, 0.29-1.15; P = .04) and 0.21 in the late screening period (95% CI, 0.09-0.48; P = .001). Most of the reduced mortality was due to fewer cases of sudden death from cardiomyopathies (from 1.50/100 000 person-years in the prescreening period to 0.15/100 000 person-years in the late screening period; P for trend = .002). During the study period, 879 athletes (2.0%) were disqualified from competition due to cardiovascular causes at the Center for Sports Medicine: 455 (2.0%) in the early screening period and 424 (2.1%) in the late screening period. The proportion of athletes who were disqualified for cardiomyopathies increased from 20 (4.4%) of 455 in the early screening period to 40 (9.4%) of 424 in the late screening period (P = .005). Conclusions. The incidence of sudden cardiovascular death in young competitive athletes has substantially declined in the Veneto region of Italy since the introduction of a nationwide systematic screening. Mortality reduction was predominantly due to a lower incidence of sudden death from cardiomyopathies that paralleled the increasing identification of athletes with cardiomyopathies at preparticipation screening.

Author Affiliations: Department of Cardiac, Thoracic, and Vascular Sciences (Drs Corrado and Pavei) and Institute of Pathological Anatomy (Drs Basso and Thiene), University of Padua Medical School; and Center for Sports Medicine and Physical Activity (Drs Michieli and Schiavon), Padua, Italy.

JAMA. Vol. 296 No. 13, October 4, 2006

Sudden Cardiac Death

 
How Sudden Is Sudden Cardiac Death?

Dirk Müller, MD, PhD; Rahul Agrawal, MD, PhD; Hans-Richard Arntz, MD, PhD

From Medizinische Klinik II, Kardiologie und Pulmologie, Charité, Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany.

Background— Out-of-hospital sudden cardiac death (SCD) is a frequent cause of death. Survival rates remain low despite increasing efforts in medical care. Better understanding of the circumstances of SCD could be helpful in developing preventive measures and facilitating proper reactions to such a pending event.

Methods and Results— Information on cases of out-of-hospital SCD was collected in the Berlin, Germany, emergency medical system via a questionnaire. Bystander interviews were performed by the emergency physician on scene immediately after declaration of death or return of circulation. Of 5831 rescue missions, 406 involved patients with presumed cardiac arrest. Sixty-six percent had a known cardiac disease. In 72%, the arrest occurred at home, and in 67%, it occurred in the presence of an eyewitness. Information on symptoms immediately preceding the arrest was available in 80% (n=323) of all 406 patients and in 274 of those with witnessed arrest. Symptoms were identical in the 2 groups. Typical angina was present for a median of 120 minutes in 25% of the 274 patients with witnessed arrest and in 33% with a symptom duration of less than 1 hour.

Conclusions— SCD occurs most often at home in the presence of relatives and after a longer period of typical warning symptoms. Although the much-hailed use of public access defibrillation is supported by several studies, the present results raise the question of whether educational measures and targeted educational programs tailored for patients at risk and their relatives should have a higher priority.

Circulation. 2006;114:1146-1150.
© 2006 American Heart Association, Inc.

http://circ.ahajournals.org

Hypertension renal: experiment

Uninephrectomy in Young Age or Chronic Salt Loading Causes Salt-Sensitive Hypertension in Adult Rats

Mattias Carlström; Johan Sällström; Ole Skøtt; Erik Larsson; A. Erik G. Persson
From the Department of Medical Cell Biology (M.C., J.S., A.E.G.P.), Division of Integrative Physiology, and the Department of Genetics and Pathology (E.L.), Uppsala University, Uppsala, Sweden; and the Department of Physiology and Pharmacology (O.S.), University of Southern Denmark, Odense, Denmark.

The importance of nephron endowment and salt intake for the development of hypertension is under debate.
The present study was designed to investigate whether reduced nephron number, after completion of nephrogenesis, or chronic salt loading causes renal injury and salt-sensitive hypertension in adulthood. Rats were operated at 3 weeks of age (after completed nephrogenesis) and then subjected to either normal or high-salt diets for 6 to 8 weeks.
Four different experimental groups were used: sham-operated animals raised with normal-salt diet (controls) or high-salt diet (HS) and uninephrectomized animals raised with normal-salt diet (UNX) or high-salt diet (UNX+HS).
In the adult animals, renal and cardiovascular functions were evaluated and blood pressure recorded telemetrically under different sodium conditions (normal, high, and low).
Hypertension was present in UNX+HS (122±9 mm Hg), UNX (101±3 mm Hg), and HS (96±1 mm Hg) groups on normal-salt diets compared with the controls (84±2 mm Hg), and the blood pressure was salt sensitive (high- versus normal-salt diet; 23±3, 9±2, 7±2, and 1±1 mm Hg, respectively).
The hypertensive groups (UNX+HS, UNX, and HS) had increased diuresis and reduced ability to concentrate urine.
The glomerular filtration rate (milliliters per minute) in anesthetized rats was reduced in the UNX+HS (2.36±0.30) and UNX animals (2.00±0.31) compared with both HS animals (3.55±0.45) and controls (3.01±0.35).
Hypertensive groups displayed reduced plasma renin concentrations during high sodium conditions and hypertrophic kidneys and hearts with various degrees of histopathologic changes.
In conclusion, at a young age after completed nephrogenesis, uninephrectomy or chronic salt loading causes renal and cardiovascular injury with salt-sensitive hypertension.

Key Words: blood pressure • cardiovascular diseases • fibrosis • glomerular filtration rate • hypertension renal • nephrectomy • sodium dietary

Hypertension, June, 2007,Vol.49, №6; p.1342.
© 2007 American Heart Association, Inc.

Posterior circulation stroke in childhood

Posterior circulation stroke in childhood

Risk factors and recurrence

V. Ganesan, MD, W. K. Chong, MD, T. C. Cox, MB, S. J. Chawda, MB BCh, M. Prengler, MD and F. J. Kirkham, MB BChir

From the Neurosciences Unit (Drs. Ganesan, Prengler, and Kirkham), Institute of Child Health, University College London, and Great Ormond Street Hospital for Children NHS Trust; and Department of Neuroradiology (Drs. Chong, Cox, and Chawda), Great Ormond Street Hospital for Children NHS Trust, London, UK.

Objective: To ascertain whether posterior circulation stroke in children has distinctive clinical or radiologic features.

Methods: Patients were identified retrospectively from two pediatric neurology centers. Clinical details were ascertained by chart review, and radiologic data were reviewed by three neuroradiologists.

Results: Twenty-two cases were identified (17 boys). Twenty children had evidence of vertebrobasilar arterial abnormalities, which were multifocal in 12. The etiology of these was vertebral artery dissection in 10 cases and unclear in the remaining 10. Cardiac abnormalities were rare (n = 4). Other risk factors for stroke in childhood were hypertension (n = 9), the thermolabile methylene tetrahydrofolate reductase gene mutation (n = 4), and the factor V Leiden mutation (n = 2). Two children had subluxation of the upper cervical spine at the extreme of normal limits. In follow-up for 6 months to 11 years (median 4 years), five patients had further strokes and seven had TIA. Overall, 12 patients had no residual neurologic deficits.

Conclusions: The male preponderance, frequency of arterial dissection, rarity of cardiac embolism, and >20% recurrence were notable. Cerebral angiography is usually indicated if a definitive diagnosis is not made on MRI. Additional investigations should include echocardiography and cervical spine radiography in flexion and extension.

Neurology 2002;59:1552-1556
© 2002 American Academy of Neurology
http://www.neurology.org/

Risk for myocardial infarction

Left Ventricular Hypertrophy, Subclinical Atherosclerosis, and Inflammation

Sameer K. Mehta; J. Eduardo Rame; Amit Khera; Sabina A. Murphy; Russell M. Canham; Ronald M. Peshock; James A. de Lemos; Mark H. Drazner
From the Donald W. Reynolds Cardiovascular Clinical Research Center and Divisions of Cardiology (S.K.M., J.E.R., A.K., R.M.C., R.M.P., J.A.d.L., M.H.D.), Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas; and the TIMI Study Group (S.A.M.), Boston, Mass.

To elucidate mechanisms by which left ventricular (LV) hypertrophy (LVH) increases the risk of atherosclerotic heart disease, we sought to determine whether LVH is independently associated with coronary artery calcium (CAC) and serum C-reactive protein (CRP) levels in the general population. The Dallas Heart Study is a population-based sample in which 2633 individuals underwent cardiac MRI to measure LV structure, electron beam CT to measure CAC, and measurement of plasma CRP. We used univariate and multivariable analyses to determine whether LV mass and markers of concentric LV hypertrophy or dilation were associated with CAC and CRP. Increasing quartiles of LV mass indexed to fat-free mass, LV wall thickness, and concentricity, but not LV volume, were associated with CAC in both men and women (P<0.001). After adjustment for traditional cardiovascular risk factors and statin use, LV wall thickness and concentricity remained associated with CAC in linear regression (P<0.001 for each). These associations were particularly robust in blacks. LV wall thickness and concentricity were also associated with elevated CRP levels (P=0.001 for both) in gender-stratified univariate analyses, although these associations did not persist in multivariable analysis. In conclusion, concentric LVH is an independent risk factor for subclinical atherosclerosis. LVH is also associated with an inflammatory state as reflected in elevated CRP levels, although this relationship appears to be mediated by comorbid conditions. These data likely explain in part why individuals with LVH are at increased risk for myocardial infarction.

Key Words: left ventricular hypertrophy • atherosclerosis • inflammation • myocardial infarction • coronary artery disease

Hypertension, June, 2007,Vol.49, №6; p.1385.
© 2007 American Heart Association, Inc.

Hypoadiponectinemia: Predictor of Hypertension

Hypoadiponectinemia as a Predictor for the Development of Hypertension: A 5-Year Prospective Study

Wing-Sun Chow; Bernard M.Y. Cheung; Annette W.K. Tso; Aimin Xu; Nelson M.S. Wat; Carol H.Y. Fong; Liza H.Y. Ong; Sidney Tam; Kathryn C.B. Tan; Edward D. Janus; Tai-Hing Lam; Karen S.L. Lam
From the Department of Medicine (W-S.C., B.M.Y.C., A.W.K.T., A.X., N.M.S.W., C.H.Y.F., L.H.Y.O., K.C.B.T., K.S.L.L.), the Research Centre of Heart, Brain, Hormone, and Healthy Aging (B.M.Y.C., A.X., K.C.B.T., K.S.L.L.), the Clinical Biochemistry Unit (S.T., E.D.J.), and the Department of Community Medicine (T-H.L.), University of Hong Kong, Queen Mary Hospital, Hong Kong, People’s Republic of China. Current address: Department of Medicine (E.D.J.), University of Melbourne, Western Hospital, Footscray, Australia.

Low circulating levels of adiponectin, an adipokine with insulin-sensitizing, antiatherogenic, and anti-inflammatory properties, are found in hypertensive patients. Adiponectin replenishment ameliorated hypertension in adiponectin-deficient mice or obese, hypertensive mice with hypoadiponectinemia, suggesting an etiologic role of adiponectin in hypertension.

We aimed to determine, in this 5-year prospective study, whether hypoadiponectinemia could predict the development of hypertension in a nondiabetic Chinese cohort. A total of 577 subjects (249 men and 328 women) were recruited from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study and prospectively followed up for 5 years.

The relationship of serum adiponectin with the development of hypertension (sitting blood pressure 140/90 mm Hg) was investigated in a nested case–control study consisting of 70 subjects who had developed hypertension on follow-up and 140 age- and sex-matched control subjects who were normotensive both at baseline and at year 5. At baseline, serum adiponectin level in the lowest sex-specific tertile was more likely to be associated with hypertension (P=0.003 versus the highest tertile, after adjusting for age, body mass index, fasting insulin, and high-sensitivity C-reactive protein).
At year 5, baseline serum adiponectin was a significant independent predictor of incident hypertension in the nested case–control study (P=0.015; age adjusted), together with mean arterial pressure (P<0.001), high-sensitivity C-reactive protein (P=0.018), and body mass index (P=0.004). Normotensive subjects with baseline serum adiponectin levels in the lowest sex-specific tertile had an increased risk of becoming hypertensive (adjusted odds ratio: 2.76; 95% CIs: 1.06 to 7.16; P=0.037 versus highest tertile).

Our data suggest that hypoadiponectinaemia may be involved in the pathogenesis of hypertension in humans.

Key Words: adiponectin • hypertension • Chinese • prediction • C-reactive protein

Hypertension, June, 2007,Vol.49, №6; p.1455.
© 2007 American Heart Association, Inc.

Obesity-Induced Hypertension: Activation Baroreflex

Prolonged Activation of the Baroreflex Abolishes Obesity-Induced Hypertension

Thomas E. Lohmeier; Terry M. Dwyer; Eric D. Irwin; Martin A. Rossing; Robert S. Kieval
From the Department of Physiology (T.E.L., T.M.D.), University of Mississippi Medical Center, Jackson; Trauma Services (E.D.I.), North Memorial Medical Center, Robbinsdale, Minn; and CVRx, Inc. (M.A.R., R.S.K.), Maple Grove, Minn.

Prolonged electrical activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure in normotensive dogs.
The main goal of this study was to assess the influence of prolonged baroreflex activation on arterial pressure and neurohormonal responses in 6 dogs with obesity-induced hypertension.
After control measurements, the diet was supplemented with cooked beef fat for 6 weeks, whereas sodium intake was held constant. After 4 weeks of the high-fat diet, there were increments in body weight from 25.8±0.7 to 38.6±1.0 kg, mean arterial pressure from 97±2 to 110±3 mm Hg, heart rate from 67±3 to 91±4 bpm, and plasma norepinephrine concentration from 141±35 to 280±52 pg/mL. Plasma glucose and insulin concentrations were elevated, but increases in plasma renin activity during the initial weeks of the high-fat diet were not sustained. During week 5, baroreflex activation resulted in sustained reductions in mean arterial pressure, heart rate, and plasma norepinephrine concentration; at the end of week 5, these values were 87±2 mm Hg, 77±4 bpm, and 166±45 pg/mL, respectively. These suppressed values returned to week 4 levels during a 7-day recovery period after baroreflex activation. There were no changes in plasma glucose or insulin concentrations, or plasma renin activity during prolonged baroreflex activation.
These findings indicate that baroreflex activation can chronically suppress the sympathoexcitation associated with obesity and abolish the attendant hypertension while having no effect on hyperinsulinemia or hyperglycemia.

Key Words: baroreflex • hypertension • heart rate • obesity • sympathetic nervous system • norepinephrine • renin–angiotensin system

Hypertension, June, 2007,Vol.49, №6; p.1307.
© 2007 American Heart Association, Inc.

Hypertension and Polycystic ovary syndrome

Relationship Between Androgen Levels and Blood Pressure in Young Women With Polycystic Ovary Syndrome

Mei-Jou Chen; Wei-Shiung Yang; Jehn-Hsiahn Yang; Chi-Ling Chen; Hong-Nerng Ho; Yu-Shih Yang
Departments of Obstetrics and Gynecology (M.-J.C., J.-H.Y., H.-N.H., Y.-S.Y.) and Internal Medicine (W.-S.Y.), National Taiwan University Hospital, Taipei, Taiwan, Republic of China; Graduate Institute of Clinical Medicine (M.-J.C., W.-S.Y., C.-L.C.), College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; and the Institute of Biomedical Science (W.-S.Y.), Academia Sinica, Taipei, Taiwan, Republic of China

The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS.
Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP).
In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index–adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: 19%) in women with PCOS increased the risk of elevated blood pressure (SBP 130 mm Hg and/or DBP 85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles.
Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.

Key Words: polycystic ovary syndrome • testosterone • systolic blood pressure • diastolic blood pressure • hypertension

Hypertension, June, 2007,Vol.49, №6; p.1442.
© 2007 American Heart Association, Inc.

Maternal smoking in pregnancy

Similar Associations of Parental Prenatal Smoking Suggest Child Blood Pressure Is Not Influenced by Intrauterine Effects

Marie-Jo A. Brion; Sam D. Leary; George Davey Smith; Andy R. Ness
Departments of Social Medicine (M.-J.A.B., S.D.L., G.D.S.) and Oral and Dental Science (A.R.N.), University of Bristol, Bristol, United Kingdom

Maternal smoking in pregnancy may be associated with higher offspring blood pressure; however, results of previous studies have been inconsistent and included varying confounder adjustments.
We studied the association between maternal smoking in pregnancy and offspring blood pressure at 7 years in the Avon Longitudinal Study of Parents and Children, accounting for important social and environmental confounders and using partner smoking to investigate intrauterine effects.
Analysis was carried out in 6509 children with maternal smoking data and 7149 children with partner smoking data. In models adjusting for child age and sex, modest differences in systolic blood pressure were observed between children of mothers who did and did not smoke during pregnancy (ß=0.64 mm Hg; 95% CI: 0.09 to 1.20; P=0.02). Adjusting for all of the confounders attenuated this difference toward the null (ß=0.05 mm Hg; 95% CI: –0.59 to 0.68; P=0.9), mostly because of adjustment for breastfeeding, maternal education, and family social class.
Associations were similar between maternal and partner smoking with offspring systolic blood pressure (for partner smoking: ß=0.62 mm Hg; 95% CI: 0.17 to 1.07; P=0.07 minimally adjusted and ß=0.26 mm Hg; 95% CI: –0.36 to 0.87; P=0.4 fully adjusted), providing further evidence that differences in child blood pressure observed in minimally adjusted models are not because of a biological influence of maternal smoking on the intrauterine environment.

Keywords: ALSPAC • blood pressure • child • confounding factors (epidemiology), cohort • maternal smoking • prenatal exposure delayed effects

Hypertension, June, 2007,Vol.49, №6; p.1422.
© 2007 American Heart Association, Inc.