Anders Bergbrant

Relation of central hemodynamics to obesity and body fat distribution

Central obesity increases the risk for cardiovascular disease, but little is known about its hemodynamic effects. The aims were to investigate the influence of obesity (as defined by body mass index) and abdominal fat accumulation (as defined by the waist/hip ratio) on hemodynamics at rest and during mental stress. Invasive hemodynamic studies were performed in 20 healthy, normotensive young men (aged 18-22 years) recruited from an unbiased population sample. Their body mass index and waist/hip ratio ranged between 18.5 and 30.2 (mean 24.1) and 0.77 and 0.98 (mean 0.87), respectively. Hemodynamics were related to the two anthropometric indexes by bivariate regression analyses. Cardiac output and stroke volume were positively correlated to body mass index (p = 0.05 and p = 0.005), but inversely to waist/hip ratio (p = 0.01 and p = 0.01). Mental stress augmented the hemodynamic patterns. Total peripheral resistance during stress correlated inversely to body mass index (p = 0.02), whereas high waist/hip ratio was associated with higher systemic vascular resistance p = 0.002). The delta CO/delta MAP ratio, i.e., relative contribution of cardiac output for the stress-induced increase in mean arterial pressure, showed a strong positive association with body mass index (p = 0.004), but was inversely related to the waist/hip ratio (p = 0.002). Serum insulin correlated significantly to the stress-induced change in total peripheral resistance (r = 0.54; p = 0.02), whereas the increase in cardiac output was inversely related to insulin (r = -0.59; p = 0.007). Thus, central obesity is associated with a specific hemodynamic pattern characterized by higher total peripheral resistance, lower cardiac output, and a vasoconstrictor response to psychosocial stress.

Enhanced Levels of Tissue-Type Plasminogen Activator in Borderline Hypertension

Despite effective antihypertensive therapy, essential hypertension is still associated with considerable residual risk of cardiovascular complications. The aim of the present study was to investigate the state of the endogenous fibrinolytic system in young subjects with borderline hypertension. Thirty-nine young (age, 24 to 34 years) male subjects with borderline hypertension (systolic BP [SBP] 140 to 160 mm Hg and/or diastolic BP [DBP] 85 to 95 mm Hg) and 17 normotensive control subjects (age, 22 to 31 years; SBP 110 to 130 and DBP 60 to 80 mm Hg) were recruited from a population screening. Plasma levels of tissue-type plasminogen activator (t-PA) antigen and activity and plasminogen activator inhibitor 1 (PAI-1) antigen were determined at rest and in response to a venous occlusion test. Borderline-hypertensive subjects had metabolic and anthropometric characteristics similar to normotensive individuals. In comparison with normotensive subjects, borderline-hypertensive subjects had higher plasma concentration of t-PA antigen both at rest and after venous occlusion but similar levels of t-PA activity or PAI-1 antigen. The increase in t-PA antigen and activity in response to venous occlusion was significantly greater in borderline-hypertensive subjects than in normotensive control subjects (P < .0001 and P = .003, respectively). In stepwise regression analyses, 24-hour mean arterial pressure emerged as the single most powerful predictor of t-PA antigen levels, but body mass index was the most important determinant of t-PA activity and PAI-1 antigen. However, PAI-1 was explained by both body mass index (partial r = .48, P < .001) and 24-hour mean arterial pressure (partial r = .29, P < .05). Thus, early hypertension may be associated with significant alterations in endogenous fibrinolysis.

The effect of transcutaneous electric nerve stimulation in patients with therapy- resistant hypertension

Objectives: Afferent nerve stimulation, such as acupuncture and transcutaneous electric nerve stimulation (TENS), has shown a blood pressure reduction in both animal and man. In the present open and non-controlled study we investigated the effect on 24-h ambulatory blood pressure of low frequency TENS in a group of hypertensive subjects who do not respond properly to pharmacological treatment.Method: Twelve patients were investigated. The patients were treated with TENS at two acupoints on both forearms for 30 min twice daily during 4 weeks. 24-hour ambulatory blood pressure monitoring was recorded 1 week before, at start, at the end and finally 1 week after the TENS treatment.Results: The blood pressure did not change significantly during the run-in period. After 4 weeks of TENS, the mean systolic blood pressure decreased by 6.3 mm Hg (P < 0.05) and the mean diastolic blood pressure decreased by 3.7 mm hg (P < 0.05). the blood pressure reduction remained unchanged 1 week after treatment. there was no change in mean heart rate.Conclusion: The present study suggests that continuous TENS may have additional blood pressure-lowering properties in hypertensive patients who do not respond properly to pharmacological treatment. The effect of TENS may also have a prolonged effect.

Remikiren (Ro 42-5892)—An Orally Active Renin Inhibitor in Essential Hypertension Effects on Blood Pressure and the Renin-Angiotensin-Aldosterone System

Remikiren (Ro 42-5892) is a new orally active renin inhibitor with high potency and specificity in vitro. In the present study, the drug was given in a short-term study in patients with essential hypertension, either as monotherapy or with added hydrochlorothiazide. Following a wash-out period of at least 3 weeks and then 8 days of single-blind placebo, 29 patients with essential hypertension were given remikiren 600 mg orally for 8 days. After 4 days of remikiren, hydrochlorothiazide 12.5 mg or 25 mg or placebo was added in double-blind fashion for the last 4 days. There were no significant changes in blood pressure in patients given remikiren alone. In patients given additional hydrochlorothiazide for 4 days, a marked reduction in blood pressure was observed. Remikiren effectively inhibited the plasma renin activity 24 h post-dose, whereas angiotensin II was reduced only during the first hours after drug administration. It is concluded that remikiren is orally effective. Its antihypertensive effect during short-term administration was not significant, but when given with a diuretic, a marked potentiation occurred. Further studies are needed to establish the long-term effects of remikiren alone and in combination therapy.

Long-term stability of blood pressure and pressor reactivity to mental stress in borderline hypertension

Borderline hypertension is characterized by pressor hyperreactivity to mental stress. However, it has not been shown whether blood pressure hyperresponsiveness is a temporary phenomenon due to situational anxiety or a stable feature of the borderline hypertensive state. We therefore evaluated the long-term stability of invasively assessed blood pressure and central hemodynamic responses to mental stress in 10 young male subjects with borderline hypertension recruited from a population screening. Two identical 10-min mental arithmetic stress tests were performed 50 to 62 months apart (median, 4 years 8 months). Intraarterial blood pressure was monitored continuously before, during, and after stress. Cardiac output was measured by the indocyanine green dye dilution technique and indexed for body surface area. Total peripheral resistance index was computed from cardiac index and mean arterial pressure. During the 4-year follow-up period, none of the central hemodynamic parameters had changed significantly, either with respect to rest or stress levels. Test-retest variability of blood pressure measures was low, and errors of measurement ranged between 4.8 and 8.2 mm Hg for blood pressure levels at rest and during stress. Mental arithmetic induced highly significant blood pressure increments on both occasions (ANOVA, P < .0001 throughout). Pressor responses were somewhat but not significantly lower during the second test. Errors of measurement for absolute blood pressure reactivity ranged between 3.9 and 7.1 mm Hg. Intersession correlation coefficients for blood pressure levels attained during stress were above r = 0.75 throughout (P < or = .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired Glucose Tolerance at Five-year Follow-up of Young Men with Borderline Hypertension

BACKGROUND Recent studies suggest that patients with essential hypertension have impaired glucose tolerance and are hyperinsulinemic compared with normotensive subjects. The aims of the study were (1) to follow blood pressures of 56 young men with borderline hypertension for 5 years, (2) to investigate glucose tolerance in these subjects, and (3) to determine the relation of insulin/glucose metabolism to structural vascular changes and hemodynamic patterns in borderline hypertension. METHODS Thirty-nine young (age 22-34 years) male subjects with borderline hypertension (SBP 140-160 and or DBP 85-95 mmHg initially) and 17 normotensive control subjects (SBP 110-130 and DBP 60-80 mmHg) participated in the study. Blood pressure was measured, a standard oral glucose tolerance test (OGTT) was performed, and glucose, insulin and C-peptide were determined before and 30, 60, 90 and 120 minutes after a standard 75-g glucose load. Post-ischemic forearm vasodilatory responses were examined by plethysmography. RESULTS At follow-up, the borderline hypertensives had maintained significantly higher blood pressures than control subjects. Borderline hypertensives also had significantly impaired glucose tolerance compared to control subjects. The insulin response had a somewhat more sluggish descent, but did not differ significantly from the response of normotensives. The C-peptide response pattern resembled that of insulin, but C-peptide was significantly elevated after 120 min. On the whole group level, there were only weak relations of insulin to blood pressure. By contrast, fasting insulin and post-load insulin levels were strongly correlated with body mass index, the waist-hip circumference ratio, triglyceride, and both total and LDL cholesterol. Across the whole group, there were significant correlations between forearm minimal vascular resistance and fasting insulin (r = +0.37 p = 0.007) and insulin area-under-the-curve (r = +0.28 p = 0.044). However, Rmin was even more strongly correlated with body mass index, suggesting that this relationship was related to degree of obesity. CONCLUSION Borderline hypertension in young men is a persistent condition which is associated with impaired glucose tolerance without hyperinsulinemia. This finding suggests that impaired glucose tolerance might be a more primary phenomenon in early hypertension devoid of lipid metabolic aberrations.