Prevalence and clinical significance of isolated ambulatory hypertension in young subjects screened for stage 1 hypertension.

Palatini P, Winnicki M, Santonastaso M, Mos L, Longo D, Zaetta V, Dal Follo M, Biasion T, Pessina AC.

Clinica Medica 4, University of Padova, via Giustiniani, 2-35128 Padova, Italy. palatini unipd.it

Little is known about the clinical significance of isolated ambulatory hypertension, a condition characterized by low office but elevated ambulatory blood pressure. This study aimed to investigate the prevalence and the predictive value of isolated ambulatory hypertension diagnosed after 3 months of observation for the development of sustained hypertension within a cohort of 871 never-treated stage-1 hypertensive subjects. The study end point was progression to more severe hypertension and need of antihypertensive medication. In 244 subjects (28%), clinic blood pressure declined to <140/90 mm Hg after 3 months. Of these, 124 (14.2% of total) had low clinic and ambulatory blood pressures after 3 months (nonhypertensive subjects), whereas 120 subjects (13.8% of total) showed low clinic but elevated ambulatory blood pressure (isolated ambulatory hypertension). During the 6 years of observation, the number of end points based on multiple clinic blood pressure readings progressively increased from the nonhypertensive subjects (19%) to the subjects with isolated ambulatory hypertension (35%) and to the subjects with high clinic and high ambulatory blood pressures (65%, P<0.0001). In an adjusted proportional hazard model, isolated ambulatory hypertension status was associated with a 2.2 (P=0.02) increase in the risk of reaching the end point in comparison with the nonhypertensive subjects. Final ambulatory systolic blood pressure was also higher in the former than the latter (P=0.03). Our results indicate that among subjects screened for stage 1 hypertension, individuals with isolated ambulatory hypertension after 3 months of observation have increased risk of developing sustained hypertension in later life compared with subjects in whom both clinic and ambulatory blood pressures are normal.

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Hemodynamic responses to epinephrine-containing local anesthetic injection and to emergence from general anesthesia in transsphenoidal hypophysectomy patients.

Pasternak JJ, Atkinson JL, Kasperbauer JL, Lanier WL.

Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Patients undergoing transsphenoidal pituitary surgery may experience hypertensive episodes during the intranasal injection of vasoconstrictor-supplemented local anesthetics or emergence from general anesthesia. The present research characterized the blood pressure responses during transsphenoidal surgery and tested the hypothesis that the underlying pituitary disease influences the incidence and magnitude of the blood pressure responses. The records of 100 patients were retrospectively reviewed. All had direct blood pressure measurements recorded using a computer-based anesthesia recording system. Mean age was 49 +/- 17 years (+/- SD) and 52% were male. Blood pressure increased by 60 +/- 37 mm Hg systolic and 23 +/- 22 mm Hg diastolic with intranasal injection and 42 +/- 24 mm Hg systolic and 23 +/- 16 mm Hg diastolic during emergence from general anesthesia. Systolic blood pressure increased by greater than 50% in 58% of patients following intranasal injection and in 33% of patients upon emergence from anesthesia. Blood pressure responses did not differ with respect to endocrinopathy type (Cushing's disease, acromegaly, or other pathology), gender, age, surgeon, history of prior transsphenoidal surgery, history of either hypertension or diabetes, or preoperative use of either beta-adrenergic or calcium channel-blocking drugs. There was poor correlation between the epinephrine dose injected (range 30-220 microg) and systolic blood pressure response (r = 0.24; r2 = 0.06; P = 0.031). Blood pressure increases were not associated with cardiac arrhythmias, persistent myocardial ischemia, or myocardial infarction. The authors conclude that in transsphenoidal hypophysectomy patients, large blood pressure increases are common with intranasal injection and upon awakening from general anesthesia. However, the authors were not able to find a variable that might enable the prediction of which patients are most likely to experience the most intense blood pressure elevations.

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The G(894)-T(894) polymorphism in the gene for endothelial nitric oxide synthase and blood pressure in lead-exposed workers from Korea.

Lustberg ME, Schwartz BS, Lee BK, Todd AC, Silbergeld EK.

Department of Epidemiology and Preventive Medicine, University of Maryland Baltimore, Baltimore, Maryland 21205, USA.

We evaluated whether the G -T polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS) gene is associated with blood pressure or modifies the relation between lead dose and blood pressure in 803 lead workers in Korea. A total of 84.9% of individuals were homozygous GG, 14.4% heterozygous GT, and 0.8% homozygous TT. The T allele was not significantly associated with systolic or diastolic blood pressure. The prevalence of hypertension did not differ by T status (OR = 0.82; 95% CI = 0.50-1.37). There was no evidence of effect modification by eNOS genotype on relations of lead dose with blood pressure. These data provide no evidence that the T allele is associated with higher blood pressure or modifies the association of lead dose with blood pressure.

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Association between factor VII polymorphisms and blood pressure: the Stanislas Cohort.

Sass C, Blanquart C, Morange PE, Pfister M, Visvikis-Siest S.

Unite INSERM U525, Faculte de Pharmacie, Centre de Medecine Preventive, and Universite Henri Poincare, Nancy, France.

The purpose this study was to determine whether Arg353Gln and -323Del/Ins polymorphisms of factor VII (FVII) are related to blood pressure levels and hypertension. Subjects were drawn from the Stanislas Cohort, a longitudinal, familial French cohort examined twice since 1994. The "blood pressure study" included 1342 subjects free of medication use that could affect blood pressure. The "hypertension study" included 645 normotensive and 77 hypertensive adult subjects. Association with hypertension was also studied in 547 hypertensives enrolled in a clinical trial and in 624 normotensives drawn from the Stanislas Cohort. In the "blood pressure study," parents with the 353Gln or -323Ins allele had lower blood pressures than did noncarriers at each examination, independent of covariates (0.01< or =P< or =0.05, except for diastolic blood pressure [DBP] at baseline, where P=0.103). Similarly significant relations were observed in their offspring (P< or =0.05, except for systolic blood pressure [SBP] at 5 years, where P=0.186). In a representative subgroup of 267 individuals, the -323Del/Ins polymorphism was significantly associated with plasma FVII levels in both parents and offspring (P<0.001). FVII levels in plasma were significantly correlated with SBP and DBP in parents but not in offspring. After inclusion of both FVII levels and the -223Del/Ins in the same model in parents, only FVII levels remained significantly associated with SBP and DBP. The "hypertension study" revealed that the 353Gln and -323Ins alleles were related to decreased risk (odds ratio [OR]=0.554, 95% confidence interval [CI], 0.362 to 0.848, and OR=0.475, 95% CI, 0.299 to 0.755, respectively). These results suggest that the FVII gene may be a susceptibility locus for hypertension.

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Interaction between an 11betaHSD1 gene variant and birth era modifies the risk of hypertension in Pima Indians.

Franks PW, Knowler WC, Nair S, Koska J, Lee YH, Lindsay RS, Walker BR, Looker HC, Permana PA, Tataranni PA, Hanson RL.

Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 1550 E Indian School Rd, Phoenix, AZ 85014, USA. pfranks niddk.nih.gov

11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a candidate gene for hypertension, diabetes, and obesity through altered glucocorticoid production. This study explored the association of 11betaHSD1 gene variants with diabetes, hypertension, and obesity in a longitudinal population study of American Indians (N=918; exams=5508). In multivariate mixed models assuming an additive effect of genotype, a 5' upstream variant (rs846910) was associated with blood pressure (diastolic blood pressure beta=1.58 mm Hg per copy of the A allele, P=0.0008; systolic blood pressure beta=2.28 mm Hg per copy of the A allele, P=0.004; mean arterial blood pressure beta=1.83 mm Hg per copy of the A allele, P=0.0006) and hypertension (odds ratio=1.27 per copy of the A allele, P=0.02). However, birth date modified these associations (test for interaction: diastolic blood pressure P=0.16; systolic blood pressure P=0.007; mean arterial blood pressure P=0.01), such that the magnitude and direction of association between genotype and blood pressure changed with time. Finally, in models controlling for potential confounding by population stratification, we observed evidence of within-family effects for blood pressure (diastolic blood pressure beta=1.77 mm Hg per copy of the A allele, P=0.004; systolic blood pressure beta=2.04 mm Hg per copy of the A allele, P=0.07; mean arterial blood pressure beta=1.85 mm Hg per copy of the A allele, P=0.01) and for hypertension (odds ratio=1.26 per copy of the A allele; P=0.08). No association was observed for obesity. Associations with diabetes were similar in magnitude as reported previously but were not statistically significant. These data demonstrate association between genetic variability at 11betaHSD1 with hypertension, but these effects are modified by environmental factors.

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Effect on rat arterial blood pressure of chemically generated peroxyl radicals and protection by antioxidants.

Peluso I, Serafini M, Campolongo P, Palmery M.

Department of Pharmacology of Natural Substances and General Physiology, "La Sapienza" University, P.le Aldo Moro 5, 00185 Rome, Italy.

Convincing evidence suggests that blood redox changes play a role in the development of various cardiovascular disorders including hypertension. Nutritional antioxidants have been suggested to play a role in cardiovascular disease prevention. In this study, we investigated in vivo changes in rat arterial blood pressure induced by acute exposition to an increased load of peroxyl radicals and by the administration of selected antioxidants after chemically induced oxidative stress. Hydrosoluble and liposoluble peroxyl radicals, generated by 2,2'-azobis-(2-amidinopropane) dihydrochloride and 2,2'-azobis 2,4-di-methylvaleronitrile, induced a dose-dependent decrease in rat blood pressure. All antioxidants tested (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, vitamin C, glutathione and dithiothreitol) returned peroxyl radical-induced hypotension to normal. Of the various antioxidants tested, glutathione was the most effective in restoring blood pressure after peroxyl radical generation. Treatment of rats with a thiol-chelating agent (N-ethylmaleimide) and an oxidizing agent (5,5'-dithiobis-2-nitrobenzoic) inhibited peroxyl radical-mediated hypotension. Our results suggest that acute exposition to peroxyl radicals have a hypotensive effect on blood pressure and that thiols play an active role in the redox regulation of blood pressure. Other experiments are needed to clarify the role played by oxidative potentials on blood pressure and the mechanism of action of nutritional antioxidants.

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[The stakes of force perseverance training and muscle structure training in rehabilitation. Recommendations of the German Federation for Prevention and Rehabilitation of Heart-Circulatory Diseases e.v.]

[Article in German]

Bjarnason-Wehrens B, Mayer-Berger W, Meister ER, Baum K, Hambrecht R, Gielen S; German Federation for Cardiovascular Prevention and Rehabilitation.

Institut fur Kreislaufforschung und Sportmedizin, Deutsche Sporthochschule Koln, Carl-Diem-Weg 6, 50933, Cologne, Germany. bjarnason dshs-koeln.de

While aerobic endurance training has been a substantial part of international recommendations for cardiac rehabilitation during the last 30 years, there is still a rather reserved attitude of the medical community to resistance exercise in this field. Careful recommendations for resistance exercise in cardiac patients was only published a few years ago. It has been taken for granted that strength exercise elicits a substantial increase in blood pressure and thus imposes, especially in cardiac patients, a risk of potentially fatal cardiovascular complications. Results of the latest studies show that the existing recommended overcaution is not justified. Strength exercise can indeed result in extreme increases of blood pressure, but this is not the case for all loads of this kind. The actual blood pressure response to strength exercise depends on the isometric component, the exercise intensity (load or resistance used), muscle mass activated, the number of repetitions in the set and/or the duration of the contraction as well as involvement of Valsalva maneuver. Intra arterially performed blood pressure measurements during resistance exercise in patients with heart disease showed that strength training carried out at low intensities (40-60% of MVC) and with high numbers of repetitions (15-20) only evokes a moderate increase of blood pressure comparable with blood pressure measures induced by moderate endurance training. If used properly and performed accurately, individually dosed, medically supervised and controlled through experienced sport therapists, a dynamic resistance exercise is-at least for a certain group of patients-not associated with higher risks than an aerobic endurance training and can in addition to endurance training improve muscle force and endurance, have a positive influence on cardiovascular function, metabolism, cardiovascular risk factors as well as psychosocial well-being and overall quality of life. However, with respect to currently available data, resistance exercise cannot be generally recommended for all groups of patients. The appropriate kind and execution of training is highly dependent on current clinical status, cardiac capacity as well as possible accompanying diseases of the patient. Most of the studies carried out up to date included small samples of middle-aged male patients with almost normal levels of aerobic endurance performance and good left ventricular function. Data is missing for risk groups, older patients and women. Therefore, an integration of dynamic resistance exercises in cardiac rehabilitation can only be recommended without hesitation for CHD patients with high physical capacity (good myocardial function, revascularized). Since patients with myocardial ischemia and/or low left ventricular functioning might develop wall motion disturbances and/or dangerous ventricular arrhythmia when performing resistance exercises, prevalence of the following conditions is recommend: moderate to high LV-function, high physical performance (>5-6 metabolic equivalents= >1.4 watts/kg body weight) in absence of angina pectoris symptoms or ST-depression, by maintained current medication. In the proposed recommendations, a classification of risks for resistance training in cardiac rehabilitation is being made based on current data and is complemented by specific recommendations for particular groups of patients and detailed guidelines for setup and completion of the therapy program.

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Chronic thyrotropin-suppressive therapy with levothyroxine and short-term overt hypothyroidism after thyroxine withdrawal are associated with undesirable cardiovascular effects in patients with differentiated thyroid carcinoma.

Botella-Carretero JI, Gomez-Bueno M, Barrios V, Caballero C, Garcia-Robles R, Sancho J, Escobar-Morreale HF.

Department of Endocrinology, Hospital Ramon y Cajal, Madrid, Spain.

To evaluate cardiovascular functionality in patients with thyroid cancer, we have performed echocardiography and ambulatory blood pressure monitoring in 19 women with differentiated thyroid carcinoma during thyroxine withdrawal, at three time points: the last day on TSH-suppressive thyroxine doses (subclinical or mild hyperthyroidism), 4-7 days after withdrawal (normal free thyroxine (FT4) and free triiodothyronine (FT3) levels), and before 131I whole body scanning (overt hypothyroidism). Twenty-one healthy euthyroid women served as controls. When compared with the values at visit 2, when patients had normal serum FT4 and FT3 levels, night-time systolic and mean blood pressure were increased when the patients were mildly hyperthyroid, and night-time systolic, diastolic and mean blood pressure were increased during overt hypothyroidism. The proportion of nondippers (absence of nocturnal decline in blood pressure) was markedly increased compared with healthy controls (7%), when patients were hyper- or hypothyroid (58% and 50% respectively), but not when patients had normal FT4 and FT3 levels (12%). No changes were observed in office blood pressure or in daytime ambulatory blood pressure readings. Diastolic function worsened during thyroxine withdrawal (E and A waves (early and late mitral flow) decreased, and the E/A ratio and the isovolumic relaxation time increased), and cardiac output decreased in parallel with the decrease in heart rate and systolic blood flow. In conclusion, the chronic administration of TSH-suppressive doses of thyroxine and the withdrawal of thyroxine frequently used for the management of differentiated thyroid carcinoma, are associated with undesirable cardiovascular effects. Copyright 2004 Society for Endocrinology

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