Gudmund Nordby

Autonomic Function in Hypertensive and Normotensive Subjects: The Importance of Gender

Abstract—Baroreceptor reflex sensitivity (BRS) has been found lower and heart rate variability (HRV) parasympathetic markers have been found higher in healthy women than in healthy men. Thus, in the present study we hypothesized gender differences in the autonomic function among hypertensive subjects. Forty-one hypertensive patients and 34 normotensive subjects, age 53±1 years, were examined. Four weeks after cessation of antihypertensive therapy, HRV was assessed in 24-hour Holter ECGs, and BRS was calculated with the transfer technique. A t test was performed after log transformation of spectral values. Resting blood pressure and heart rate in the hypertensive and the normotensive groups were 150±2/100±1 (mean±SEM) and 121±2/81±1 mm Hg, respectively, and 68±1 and 60±1 bpm, respectively (P <0.0005). Compared with normotensive controls, hypertensive patients had lower total power (1224±116 versus 1797±241 ms2;P =0.03), lower low frequency power (550±57 versus 813±115 ms2;P =0.04), lower high frequency power (141±23 versus 215±38 ms2;P =0.06), lower root mean square successive difference (28.7±2.7 versus 35.7±3.0 ms;P =0.03), and PNN50 (4.9±0.6% versus 9.8±1.5%;P =0.003). BRS was also lower in the hypertensive subjects (7.6±0.6 versus 10.4±0.8 ms/mm Hg;P =0.005). When comparing the same parameters between normotensive subjects and hypertensive subjects within the same gender group, we found significant reduction (P <0.05) only within the female group. The difference in BRS within the female group was twice that within the male group. Stepwise multiple regression analysis revealed gender, age, HDL cholesterol, and blood pressure as independent explanatory variables of BRS and HRV. Our results suggest that gender is an important determinant of BRS and HRV. Autonomic function parameters were especially impaired in hypertensive women compared with hypertensive men.

Relationship between hemorrheologic factors and insulin sensitivity in healthy young men.

The present study aimed at testing a possible relationship between hemorrheologic factors, such as hematocrit, fibrinogen, and whole-blood viscosity, and insulin sensitivity in healthy humans. Twenty-one 21-year-old men were studied with the hyperinsulinemic euglycemic glucose clamp technique. We found statistically significant negative correlations between the glucose disposal rate (GDR) and calculated whole-blood viscosity at both high (r = -.55, P = .01) and low (r = -.51, P = .01) shear rates. We observed negative associations between GDR and fibrinogen (r = -.66, P = .002), GDR and hematocrit (r = -.63, P = .002), GDR and body mass index (r = -.51, P = .007), and GDR and resting heart rate (r = -.46, P = .04). Using stepwise multiple regression considering whole-blood viscosity, body mass index, mean arterial blood pressure, and heart rate as independent variables, we found that only whole-blood viscosity and body mass index were independent explanatory variables of the GDR. Together they accounted for 63% of the variability in the GDR in our subjects. These results suggest hemorrheologic, and therefore indirectly hemodynamic, factors as correlates to insulin sensitivity.

Insulin sensitivity, sympathetic activity, and cardiovascular reactivity in young men

The present study was undertaken to examine the relationships between insulin sensitivity, blood pressure (BP), and cardiovascular reactivity, and to assess sympathetic nervous system influence. Insulin sensitivity (GDR/I; euglycemic glucose clamp technique) was related to BP and heart rate (HR) in different situations in 40 healthy young men: in the laboratory, during a mental arithmetic stress test, and during baseline conditions at home. GDR/I correlated with supine diastolic BP in the laboratory and with maximum diastolic BP during mental stress (r = -0.46, P = .003; r = -0.62, P = .0001, respectively), but not so strongly with diastolic BP measured at home (r = -0.29, P = .09). Diastolic BP during stress and body mass index were the only independent explanatory variables of GDR/I in multiple regression analysis (multiple R = 0.71, R2 = 0.50, P < .0001). GDR/I and systolic BP were not significantly correlated at any time. GDR/I correlated negatively with HR in the laboratory and with maximum HR during mental stress, but not with HR at home. Maximum plasma epinephrine during stress correlated with stress BP and HR (r = 0.53, P = .001; r = 0.70, P < .0001, respectively) and negatively with GDR/I (r = -0.36, P < .05). In the present study, GDR/I is related to diastolic but not to systolic BP, and more closely correlated to diastolic BP and HR measured during mental stress than to diastolic BP and HR during baseline conditions at home.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship Between Insulin Sensitivity and Maximal Forearm Blood Flow in Young Men

Insulin resistance is a part of the metabolic cardiovascular syndrome. We aimed to test the hemodynamic hypothesis of insulin resistance, which suggests that a decreased skeletal muscle blood supply with subsequent reduced nutritional flow causes insulin resistance in skeletal muscle. We assessed determinants of peripheral blood flow such as maximal forearm blood flow (MFBF), minimal forearm vascular resistance (MFVR), and whole blood viscosity (WBV) in 27 young men with borderline elevation of blood pressure. Insulin sensitivity measured as glucose disposal rate (GDR) correlated with MFBF (r=0.55, P=0.003), MFVR (r=-0.58, P=0. 002), and WBV (r=-0.39, P=0.046 at shear rate 201 s-1). There was no correlation between GDR and myocardial thickness or left ventricular mass. In a stepwise multiple regression analysis, MFVR and WBV explained 54% of the variation in GDR. The relative increase in mean arterial blood pressure during a mental stress test, as a marker of reactivity or an alert reaction, was correlated with MFVR (r=0.56, P=0.002) and inversely with GDR (r=-0.45, P=0.018) and MFBF (r=-0.49, P=0.01) but not with cardiac dimensions. In a stepwise multiple regression analysis, 48% of the increase in blood pressure during a mental stress test was explained by MFVR and WBV. Fasting insulin correlated with MFVR (r=0.41, P=0.036) and GDR (r=-0.62, P=0.001). These data show a positive association between the appearance of peripheral structural vascular changes as quantified through a hemodynamic technique and insulin resistance in young men with borderline elevation of blood pressure. The cause-effect relationship of this finding needs further evaluations.

Whole Blood Viscosity, Blood Pressure and Cardiovascular Risk Factors in Healthy Blood Donors

Whole blood viscosity contributes to the total peripheral resistance and has been suggested to be a risk factor for cardiovascular disease. Whole blood viscosity was measured using a direct technique in 105 healthy blood donors and in addition to establishing our reference values, the relationship to blood pressure and other cardiovascular risk factors was assessed. Whole blood viscosity correlated with systolic blood pressure (r = 0.29, p = 0.003), cholesterol (r = 0.21, p = 0.034), cholesterol/HDL cholesterol ratio (r = 0.33, p = 0.01), triglycerides (r = 0.37, p < 0.0005), body mass index (r = 0.29, p = 0.003) and waist-hip ratio (r = 0.30, p = 0.002). Subjects with systolic blood pressure > 130 mmHg (n = 16) had higher whole blood viscosity (p = 0.017) than those with lower blood pressure. Whole blood viscosity was significantly lower in women (n = 52) than in men at all shear rates (0.045 > p > 0.001). These results suggest that even in a population of healthy normotensive blood donors of a wide age range and either gender, there are positive correlations between directly assessed whole blood viscosity and a number of the components of the metabolic cardiovascular syndrome including systolic blood pressure, weight and blood lipids.

Mental stress increases glucose uptake during hyperinsulinemia: Associations with sympathetic and cardiovascular responsiveness

Infusion of epinephrine and norepinephrine reduces insulin-mediated glucose disposal, ie, induces insulin resistance. Mental stress increases concentrations of both plasma catecholamines. However, the effect of acute mental stress on insulin-mediated glucose uptake has not been examined. We observed in pilot studies that a mental stress test (MST) during a euglycemic glucose clamp decreased blood glucose concentration. In a prospective study, euglycemic hyperinsulinemia was established during 120 minutes of glucose clamping; the subjects (N = 74) then underwent 5 minutes of intense mental arithmetics with infusion rates of glucose and insulin kept constant. During MST, plasma epinephrine and norepinephrine increased (by 0.23 +/- 0.02 and 0.50 +/- 0.05 nmol/L) together with blood pressure ([BP] by 18 +/- 8/9 +/- 1 mm Hg) and heart rate ([HR] by 21 +/- 1 beats per minute), with P less than .0001 for all changes. During mental stress, blood glucose concentration decreased by 0.4 +/- 0.1 mmol/L (P < .0001), followed by full recovery after another 10 minutes. Serum insulin was unchanged, indicating an acute but transient increase in glucose uptake. This finding was unrelated to age, sex, body mass, and BP status. Fifty-nine subjects with a decrease in glucose concentrations during MST were characterized by accentuated epinephrine response to MST (a change of 0.25 +/- 0.03 v 0.12 +/- 0.02 nmol/L, P = .001), increase in systolic BP (by 20 +/- 2 v 10 +/- 3 mm Hg, P = .008), and increase in HR (by 23 +/- 2 v 15 +/- 2 beats per minute, P = .008) as compared with 15 subjects with unchanged/increased glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between hemorheological factors and insulin sensitivity in normotensive and hypertensive premenopausal women

The present study aimed at testing a possible relationship between hemorheologic factors such as hematocrit and whole blood viscosity, and insulin sensitivity in premenopausal, hypertensive (HT), and normotensive (NT) women. Fourteen HT and 12 NT women were studied with the hyperinsulinemic euglycemic glucose clamp technique. Insulin sensitivity was similar in NT and HT (8.7 +/- 0.8 v 7.6 +/- 0.8 arbitrary units). Whole blood viscosity did not differ between the two groups at any shear rate (shear rate 5.2 sec-1: 7.5 +/- 0.4 in NT and 8.0 +/- 0.3 in HT, P = NS). Statistically significant negative correlations were observed between the insulin sensitivity index and calculated whole blood viscosity at both high (r = -0.49, P < .01) and low shear rates (r = -0.50, P < .01, n = 26). Insulin sensitivity index was also negatively correlated to body mass index in the combined groups (r = -0.40, P = .04), and to both systolic and diastolic blood pressure (r = -0.44, P = .02 and r = -0.38, P = .05, respectively). In multiple regression analysis, whole blood viscosity, body mass index, systolic, and diastolic blood pressure accounted for 39% of the variation in insulin sensitivity index, but only whole blood viscosity was an independent explanatory variable for the insulin sensitivity index. These results suggest hemorheologic, and therefore indirectly hemodynamic factors as correlates to insulin sensitivity.

Sex differences in essential hypertension

Abstract. A group of 41‐year‐old hypertensive men (n = 35, blood pressure (BP) 149.9 ± 2.1/ 98.9 ± 1.1 mmHg, mean ± SEM) who had never received treatment for their condition were compared with hypertensive women of the same age (n = 18, BP 155.9 ± 4.3/ 98.1 ± 1.6 mmHg) with comparable body mass index (BMI. 25.9 ± 0.5 vs. 24.9 ± 4.5 kg m−2) who, also, had never received treatment. The lipid profile was more atherogenic in the men, with lower HDL cholesterol (1.21 ± 0.04 vs. 1.38 ± 0.06 mmol l−1 P = 0.04), higher total cholesterol (6.04 ± 0.14 vs. 5.54 ± 0.18 mmol l−1. P = 0.04) and triglycerides (1.80 ± 0.16 vs. 0.96 ± 0.10 mmol l−1, P < 0.001). The hypertensive men had higher haemoglobin (P < 0.001) and haematocrit. Plasma catecholamines were inversely related to BMI in the women only (r = −0.52, P < 0.05 for both noradrenaline and adrenaline). Women with BMI above 25 kg m−2 had significantly lower arterial plasma adrenaline and noradrenaline than those with BMI below 25 kg m−2 (28 ± 5 vs. 78 ± 16 pg ml−1, P < 0.01 and 101 ± 17 vs. 206 ± 33 pg ml−1, P < 0.01 respectively). A negative curvelinear relationship appeared between arterial adrenaline and insulin (r = 0.49, P= 0.05).

Plasma Vasopressin, Catecholamines and Atrial Natriuretic Factor During Hemodialysis and Sequential Ultrafiltration

In 13 patients with chronic renal failure on maintenance hemodialysis, plasma vasopressin, atrial natriuretic factor, catecholamines and renin activity were measured during ordinary hemodialysis with fluid removal, and during isolated isoosmotic ultrafiltration and a subsequent isovolemic hemodialysis. Concomitant with a significant fall in serum osmolality, plasma vasopressin decreased significantly from 6.3 +/- 0.8 to 3.8 +/- 0.4 pg/ml (p < 0.05). Predialytic plasma vasopressin was significantly correlated to serum osmolality (r = 0.62, p = 0.001). No such relationship was observed after dialysis. During isolated ultrafiltration (1.25 +/- 0.13 L) through 1 hour, no change in either osmolality or vasopressin was observed, whereas atrial natriuretic factor decreased (700 +/- 136 to 564 +/- 115 pg/ml, p < 0.05). Atrial natriuretic factor was excessively high at all times, and may explain the low plasma renin activity observed in these patients even after fluid removal. No consistent changes were observed in the catecholamines during hemodialysis or ultrafiltration alone, despite marked changes in blood pressure and heart rate. Thus, even in patients with chronic renal failure osmotic regulation of vasopressin seems intact, and volume reduction through ultrafiltration causes a decrease in atrial natriuretic factor.

Hypertension and the Metabolic Cardiovascular Syndrome: Special Reference to Premenopausal Women

Summary: It has been proposed that hyperinsulinemia may not constitute a cardiovascular risk in women, and that the metabolic risk profile is less apparent in women than in men. In two different studies, we have assessed the interrelationship between classical coronary risk factors in women with untreated essential hypertension and looked for possible hypertensive-normotensive differences. Hypertensive women (HTI, 156 ± 2/98 ± 1 mm Hg, n = 18) in study I turned out to be overweight and had nearly three times higher fasting serum insulin levels than the normotensive control subjects (NTI, 118 ± 3/77 ± 2 mm Hg, n = 9). HTI women with a body mass index (BMI) above 25 kg/m2 had significant higher insulin levels than HTI women with a BMI less than 25 kg/m2, and when adjusting for BMI the hypertensive–normotensive difference in insulin levels was lost. In HTI women, the serum insulin level correlated positively to the BMI and triglycerides. In study II, insulin was positively associated with the systolic blood pressure in HTII women (150 ± 3/99 ± 1 mm Hg, n = 29), and a negative correlation appeared between the glucose/insulin ratio and the systolic as well as diastolic blood pressure. No difference was observed in BMI and insulin between HTII and NTII women (121 ± 3/79 ± 1 mm Hg, n = 18). In HTII women, plasminogen activator inhibitor (PAI-1) levels were higher and the euglobulin clot lysis time prolonged compared to NTII women. PAI-1 was positively correlated to insulin and triglycerides and negatively to high-density lipoprotein (HDL) cholesterol in HTII women. Strong associations between potential cardiovascular risk factors seem to be present even in untreated women with mild hypertension, with insulin being correlated to hypertension, BMI, fibrinolytic activity, triglycerides, and HDL cholesterol.