Paolo M. Suter

Is there a Role for the ob Gene Product Leptin in Essential Hypertension

In this study we wanted to evaluate the relationship between the ob gene product leptin and blood pressure, as well as plasma renin activity and plasma aldosterone levels. We studied 139 subjects with a mean+/-SD age of 50 +/-14 years and a body mass index of 26.5+/-5.3 kg/m2; 110 subjects had essential hypertension and 29 were healthy nonhypertensive controls. Blood pressure was measured in resting conditions in the morning and blood was drawn for the determination of the plasma renin activity, aldosterone, and leptin levels. The mean blood pressure of the population was 155/97 mm Hg. The relationship between these parameters was studied by univariate regression analysis according to gender and, whenever indicated, adjusted for age and body mass. The mean+/-SEM plasma leptin level in the whole population was 9.5+/-0.6 ng/mL (range, 1.1-43.3). Subjects with stage I hypertension had significantly higher plasma leptin levels than normotensive subjects. Systolic blood pressure correlated with the plasma leptin levels and the leptin levels adjusted for body weight in women (r = 0.422, P < .01) and nonhypertensive men (r = 0.644, P = .03) only. Plasma renin activity (r = 0.329, P = .03) and aldosterone levels (r = 0.342, P = .026) correlated with the leptin concentration. A significant relationship between the peripheral expression of the ob gene product leptin and systolic blood pressure was found in women and nonhypertensive men. In view of the multiple functions of leptin a causal relationship is postulated and potential mechanisms may involve modulatory effects of leptin on neuropeptide Y, angiotensinogen gene expression, the modulation of the autonomous nervous system, or effects on the pituitary adrenal axis. Direct relationships between both plasma renin activity and aldosterone levels and leptin support the potential importance of the relationship between leptin and blood pressure. Our observation may be of future importance for the understanding of the link between the increase in blood pressure and increasing body weight.

Metabolic effects of antihypertensive drugs.

Effects of antihypertensive drugs on metabolism: Numerous antihypertensive drugs have been reported to cause adverse metabolic effects such as glucose intolerance and abnormal lipid metabolism. Diuretics: There is a well defined relationship between diuretic treatment and impaired glucose tolerance and dyslipidaemia. These effects, which are seen with thiazide diuretics and loop diuretics but not with spironolactone, are independent of body weight but are strongly dose-related. βBlocking agents: βBlockers without intrinsic sympathomimetic activity have adverse effects on lipid metabolism, but P-blockers with intrinsic sympathomimetic activity do not. From the metabolic point of view, the latter type of p-blockers represent the ideal choice, but they are rarely used today. All types of P-blockers can cause an increase in fasting blood glucose and impaired glucose tolerance. Angiotensin converting enzyme (ACE) inhibitors and calcium antagonists: Neither ACE inhibitors nor calcium antagonists show any negative effects on glucose and/or lipid metabolism. ACE inhibitors have even been shown to improve insulin sensitivity. ACE inhibitors and calcium channel blockers are metabolically neutral, and there is evidence that combining an ACE inhibitor or calcium antagonist with a diuretic can reduce the adverse effects of the latter. Anti-oxidation: Some calcium antagonists show a dose-dependent anti-oxidative activity. Lacidipine has the greatest anti-oxidative activity of the commonly used calcium channel blockers. Among ACE inhibitors, only captopril has anti-oxidative activity. Other factors: Both genetic and modifiable factors may contribute to the metabolic effects of antihypertensive drugs.

Green tea polyphenols inhibit human vascular smooth muscle cell proliferation stimulated by native low-density lipoprotein.

This study investigated whether human vascular smooth muscle cell proliferation induced by native low-density lipoprotein (LDL) is affected by green tea catechins. Furthermore, the effects of native LDL on extracellular signal-regulated kinase (ERK) 1/2 activity were determined. Cell proliferation stimulated by native LDL was concentration-dependently inhibited by epigallocatechin, epigallocatechin-3-gallate, green tea polyphenon, and the nonspecific antioxidant N-acetylcysteine (P<0.05). Combined treatment of green tea polyphenon and N-acetylcysteine markedly potentiated the effect of each drug on vascular smooth muscle cell proliferation. ERK1/2 activity was only partly inhibited by green tea catechins alone or in combination with N-acetylcysteine (P<0.05). These data suggest that green tea constituents inhibit proliferation of human vascular smooth muscle cells exposed to high levels of native LDL. Green tea constituents and antioxidants may exert vascular protection by inhibiting human vascular smooth muscle cell growth associated with hypercholesterolemia.

Relationship between self-perceived stress and blood pressure

Objective: The importance of stress in the pathogenesis of essential hypertension is controversial. In this study we wanted to evaluate the relation between self-perceived stress and the blood pressure (BP) in a asymptomatic healthy population.Subjects and methods: A total of 1666 guests (mean ± s.d. age 50 ± 16 years) attending the air show AIR94 in Buochs, Switzerland volunteered to participate in a cross-sectional study. Using a self-administered questionnaire and visual analogue scales the individual stress perception and other cardiovascular risk behaviours/factors were assessed. BP, body weight, height, and the waist:hip ratio were measured.Results: Individual stress perception was inversely related with the systolic BP (SBP) (r = −0.12, P < 0.001). the relationship was found in both men and women and was independent of age and/or body weight. no relation was found between the diastolic bp (dbp) and stress perception. subjects with high normal bp according the jnc v classification showed a lower stress perception than did subjects with normal bp. in a multiple regression model the stress score was fourth most predictive of the sbp after body mass index, waist:hip ratio, and age followed by alcohol and fat intake.Conclusion: In this study we found an inverse association between the self-perceived stress and SBP. We suggest that the inverse association between BP and the self-perceived stress reflects a neuroendocrine and biochemical setting characterized by inadequate stress handling associated with a higher fat and alcohol intake and more abdominal fat tissue leading to a higher BP. Our data suggest that stress denial in combination with abdominal obesity, alcohol consumption, and smoking may be proxy for a high stress level.

Is an increased waist : hip ratio the cause of alcohol-induced hypertension? The AIR94 study.

Objective The mechanisms of alcohol-associated hypertension are not known. We tested the hypothesis that the alcohol-associated increase in blood pressure may be caused in part by an alcohol-induced accumulation of abdominal fat. Subjects and methods A total of 842 non-smoking men (mean±SD age 52±16 years) attending the air-show AIR94 in Bouchs, Switzerland, volunteered to participate in a cross-sectional study. Four alcohol consumption frequency categories were self-reported, together with weight changes since the age of 20 and during the last 2 years. Blood pressure, body weight, height and the waist: hip ratio were measured. Results The results showed that 83% of the subjects were alcohol-consumers. Systolic (analysis of variance, P = 0.002) and diastolic (P = 0.009) blood pressure and the waist: hip ratio (P>0.0001) increased with increasing alcohol consumption. The self-judged dietary fat intake increased significantly with increasing alcohol consumption. Weight changes over time were positively associated with alcohol consumption. In a regression model alcohol consumption was the fourth most important contributor to systolic and diastolic blood pressure as well as to an increased abdominal fat mass. Conclusion The alcohol-associated increase in blood pressure may be caused in part by an alcohol-induced accumulation of abdominal fat. Alcohol consumption favours the development of a positive energy balance and thus the abdominal deposition of fat, which is associated with an increased blood pressure. To reduce the risk of a positive energy balance and the abdominal deposition of fat, the intake of alcohol should be minimized and physical activity increased whenever possible.

Effect of Alcohol on postprandial lipemia with and without preprandial exercise

Objective: Different factors such as exercise habits and alcohol consumption may modulate postprandial lipid metabolism. What are the effects of alcohol on postprandial metabolism in untrained and trained individuals? Methods: The postprandial lipid response to an oral fat load (1 g fat per kg body weight (bw)) with and without alcohol (0.5 g/kg bw) was evaluated in physically trained healthy young men (T, n=12, mean ±SD age 27 ±3 years, BMI 21.6 ±1.4 kg/m2) after a premeal running session and in untrained healthy young men (UT, n=8, age 24 ±1 years, BMI 23.2 ±1.8 kg/m2) without a premeal exercise session. The T subjects ingested 35.5 ±2.7 g alcohol, the UT subjects 38 ±0.6 g. Fat was given as butter and the carbohydrates as marmalade and zwieback (rusk). The T subjects received 1.20 ±0.05 g fat and 1.02 ±0.04 g carbohydrates per kilogram lean body mass. The corresponding numbers for the UT subjects were 1.28 ±0.08 g and 1.20 ±0.06 g. The postprandial lipemia was observed for an eight-hour period. Results: Alcohol led to an increase to the triacylglycerol area under the curve (AUC) in the T subjects from 7.4 ±0.4 mmol/L * h on the control day to 11.3 ±0.9 mmol/L * h (p=0.001). The corresponding numbers in the UT subjects were 13.4 ±2.3 mmol/L * h to 19.4 ±3.5 mmol/L * h (p=0.004). Alcohol intake and physical activity training were the major determinants of the triacylglycerol (TG) AUC in these subjects. Conclusion: The ingestion of a high fat meal in combination with alcohol leads to an increased in the postprandial lipemia independently from the level of training. It is suggested that this unfavorable effect of alcohol and a high fat diet could be modified by fat restriction or a combination of a premeal exercise session and a higher level of physical activity training.

Alcohol consumption: a risk factor for abdominal fat accumulation in men

Abstract An increased abdominal fat mass is regarded as an independent cardiovascular risk factor. In this cross‐sectional study of 1099 men we found a significant positive association between alcohol intake and the waist/hip (W/H) ratio, an index for the abdominal fat mass. This relationship was independent of age and body weight. The results suggest that the risk of abdominal fat deposition could be minimized by a reduction of alcohol intake.

Race specific altitude effects on blood pressure

Altitude affects blood pressure (BP) depending on duration and absolute altitude of exposure. Until now changes in BP during exposure to altitude were studied only in Caucasians. It is not known whether BP is affected differently in black and white people in response to altitude. During a 6-day climb on Kilimanjaro, BP was measured in five white and four black people. All participants (mean ± s.d.: age 31 ± 8 years, body mass index 22 ± 2 kg/m2, BP 125 ± 11/84 ± 9 mm Hg) had previous similar experience of high-altitude mountaineering. In the base camp (3040 m) systolic BP (SBP) was similar in both groups (131 ± 9 vs 119 ± 8 mm Hg). During ascent until 4600 m SBP increased in all whites (6.5 ± 2.2 mm Hg) and decreased in all blacks (−7.3 ± 4.6 mm Hg; P = 0.02, blacks vs whites). During descent SBP returned to initial values in whites, whereas it decreased further in blacks. Diastolic BP (DBP) and heart rate remained constant in all participants. During ascent body weight increased in all whites (1.0 ± 0.8 kg) and decreased in all blacks (−1.9 ± 1.4 kg; P = 0.02, blacks vs whites) whereas it returned approximately to initial levels during descent: +0.8 ± 0.4 kg in blacks and −1.0 ± 1.3 kg in whites (P = 0.03, blacks vs whites). In this study changes in SBP and body weight during exposure to high altitudes varied between whites and blacks. Fluid balance, acclimatisation, physical fitness or genetics could explain these findings.

Spirulina is an effective dietary source of zeaxanthin to humans

Zeaxanthin is a predominant xanthophyll in human eyes and may reduce the risk of cataracts and age-related macular degeneration. Spirulina is an algal food that contains a high concentration of zeaxanthin. In order to determine the zeaxanthin bioavailability of spirulina for dietary supplementation in humans, spirulina was grown in nutrient solution with ²H₂O for carotenoid labelling. Single servings of ²H-labelled spirulina (4.0-5.0 g) containing 2.6-3.7 mg zeaxanthin were consumed by fourteen healthy male volunteers (four Americans and ten Chinese) with 12 g dietary fat. Blood samples were collected over a 45 d period. The serum concentrations of total zeaxanthin were measured using HPLC, and the enrichment of labelled zeaxanthin was determined using LC-atmospheric pressure chemical ionisation-MS (LC-APCI-MS). The results showed that intrinsically labelled spirulina zeaxanthin in the circulation was detected at levels as low as 10 % of the total zeaxanthin for up to 45 d after intake of the algae. A single dose of spirulina can increase mean serum zeaxanthin concentration in humans from 0.06 to 0.15 μmol/l, as shown in our study involving American and Chinese volunteers. The average 15 d area under the serum zeaxanthin response curve to the single dose of spirulina was 293 nmol × d/μmol (range 254-335) in American subjects, and 197 nmol × d/μmol (range 154-285) in Chinese subjects. It is concluded that the relative bioavailability of spirulina zeaxanthin can be studied with high sensitivity and specificity using ²H labelling and LC-APCI-MS methodology. Spirulina can serve as a rich source of dietary zeaxanthin in humans.

Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

BACKGROUND AND OBJECTIVES Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. RESULTS In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15-95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein-corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, -0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, -0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. CONCLUSIONS There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion.