Minimal Forearm Vascular Resistance Research Articles

PS-C29-7: ASSOCIATION OF SERUM LEPTIN TO ADIPONECTIN RATIO AND CARDIOVASCULAR STRUCTURAL INDICES IN ESSENTIAL HYPERTENSIVE PATIENTS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Dysregulated leptin and adiponectin profile is known to be associated with atherosclerotic disease. The evaluation of the leptin to adiponectin (L/A) ratio has been suggested as a powerful useful atherosclerotic index compared with adiponectin and leptin alone in patients with type 2 diabetes and obesity. In this study, we investigated the usefulness of L/A ratio for vascular structural abnormalities in essential hypertensive patients. Design and method: In 151 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion (UAE) less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), blood sampling, 24-hour urine collection, and 24-hour blood pressure monitoring were performed. Intima-media thickness of carotid artery (IMT) and minimal forearm vascular resistance (MVR) (wall to lumen ratio in resistance vessel) were also measured by using ultrasonography and strain-gauge plethysmography, respectively. Results: L/A ratio was higher in men than in women (1.23 ± 1.56 vs 0.73 ± 0.87, p < 0.05). There was no correlation between L/A ratio and systolic and diastolic blood pressure, and pulse rate. L/A ratio correlated positively with body mass index, triglyceride, hemoglobin A1c, HOMA-R and urinary C-peptide excretion (r = 0.57, 0.20, 0.20, 0.31, 0.27, p < 0.05, respectively) and negatively with HDL-cholesterol (r = -0.24, p < 0.05). In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p < 0.05, respectively)In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p < 0.05, respectively), whereas these indices did not associated with leptin and adiponectin individually. In multiple regression analysis, L/A ratio was an independent determinant for UAE, IMT and MVR. Conclusions: In patients with essential hypertension, L/A ratio was associated with obesity, abnormal glucose and lipid metabolism, increase in microalbuminuria, and arterial and arteriolar sclerosis. L/A ratio was considered as a useful indicator of vascular structural abnormalities in patients with essential hypertension.

Arterial stiffness and peripheral vascular resistance in offspring of hypertensive parents: influence of sex and other confounders.

Established essential hypertension is associated with increased arterial stiffness and peripheral resistance, but the extent of vascular changes in persons genetically predisposed for essential hypertension is uncertain. Participants from the Danish Hypertension Prevention Project (DHyPP) (both parents hypertensive) (n = 95, 41 ± 1 years, 53% men) were compared with available spouses (n = 45, 41 ± 1 years) using measurements of ambulatory blood pressure (BP), left ventricular mass index (LVMI), pulse wave velocity, central BP and augmentation index (AIx) in addition to forearm resting and minimal resistance [forearm resting vascular resistance (Rrest) and forearm minimal vascular resistance (Rmin)]. DHyPP patients with participating spouses had higher 24-h mean BP (94 ± 1 vs. 88 ± 1 mmHg, P < 0.01), LVMI (94 ± 3 vs. 80 ± 2 g/m, P < 0.01), central SBP (121 ± 2 vs. 111 ± 2 mmHg, P < 0.01) and AIx (16.0 ± 1.2 vs. 10.5 ± 1.7%, P < 0.01), but similar carotid-femoral pulse wave velocity (7.5 ± 0.2 vs. 7.1 ± 0.2 m/s), Rrest (53 ± 3 vs. 51 ± 3 mmHg/ml/min/100 ml) and log Rmin (0.58 ± 0.02 vs. 0.55 ± 0.02 mmHg/ml/min/100 ml) when compared with spouses. Using multiple linear regression analysis (adjusting for sex, age, BMI, creatinine clearance and 24-h BP, heart rate and sodium excretion) AIx and LVMI remained elevated in DHyPP patients [4.2% (0.7; 7.7), P = 0.02 and 6.3 g/m (0.7; 11.9), P = 0.03]. For the entire DHyPP cohort AIx, Rrest and Rmin were higher in women than men (P < 0.01), and the same was true for AIx and Rmin among spouses (P < 0.05). Furthermore, AIx was linearly associated with Rrest and Rmin. Young to middle-aged individuals genetically predisposed for essential hypertension display increased AIx and LVMI, although vascular stiffness and peripheral resistance are still normal.

Alterations in capillary morphology are found in mild blood pressure elevation

Remodeling of small resistance arteries is an early sign of target organ damage in hypertension. Peripheral capillary morphology abnormalities in hypertension are not well studied. The study objective was to determine whether altered capillary morphology is associated with SBP, DBP, or both in individuals without and with mild blood pressure elevation (SBP = 130-160 mmHg). Another objective was to determine whether capillary morphology is associated with minimum forearm vascular resistance, a measure of altered resistance artery structure. Participants included 115 nonpregnant, nondiabetic individuals 23-55 years of age. A five-component morphology score (distribution, tone, configuration, hypertrophy, and extravasates) was developed to describe fingernail bed capillaries visualized using venous congestion in digital photomicrographs. Multiple linear regression models adjusted for age, sex, race, tobacco use, hyperglycemia, dyslipidemia, and renal function were used to analyze the relationship between SBP, DBP, and minimum forearm vascular resistance with the morphology score. The total morphology score was significantly associated with SBP and DBP as well as minimum forearm vascular resistance (P < 0.005 for all). Among the five individual morphology score components, hypertrophy was significantly associated with SBP and DBP (P = 0.002 and 0.001, respectively), whereas extravasates were significantly associated with SBP only (P = 0.002). A five-component capillary morphology score is associated with SBP, DBP, and altered resistance artery structure in individuals with and without mild blood pressure elevation. These observations suggest that target organ damage at the level of the microcirculation can be detected using capillary morphology.

Plasma nitrate/nitrite levels are unchanged after long-term aerobic exercise training in older adults

Reduced nitric oxide (NO) production and bioactivity is a major contributor to endothelial dysfunction. Animal data suggest that improvements in endothelial function in response to aerobic exercise training may depend on the duration of the training program. However, no studies have examined changes in NO (as assessed by the major NO metabolites, nitrate and nitrite, NO x ) after long-term training in humans. In addition, aging may impair the ability of the vasculature to increase NO with exercise. Thus, we determined whether 24 weeks of aerobic exercise training increases plasma NO x levels in sedentary older adults. We also examined changes in forearm blood flow (FBF) at rest and during reactive hyperemia as a measure of vasomotor function. Plasma NO x levels were measured in 82 men and women using a modified Griess assay. FBF was assessed in a subset of individuals ( n = 15) using venous occlusion plethysmography. After 24 weeks of exercise training, there were significant improvements in maximum oxygen consumption, HDL cholesterol, triglycerides, and body fat. Changes in plasma NO x levels ranged from −14.83 to +16.69 μmol/L; however, the mean change overall was not significant (−0.33 ± 6.30 μmol/L, p = 0.64). Changes in plasma NO x levels were not associated with age, gender, race, HDL cholesterol, triglycerides, body weight, body fat, or maximal oxygen consumption. There were also no significant changes in basal FBF, peak FBF, hyperemic response, total hyperemic flow, or minimum forearm vascular resistance with exercise training. In conclusion, improvements in plasma NO x levels and FBF are not evident after long-term training in older adults.

Effect of verapamil, trandolapril and their combination on vascular function and structure in essential hypertensive patients

AimThe aim of the present study is to evaluate the effect of treatment with verapamil, trandolapril and their combination on peripheral microcirculation vasoreactivity. MethodsTwenty hypertensive patients were randomized to receive oral trandolapril (4mg oid; TRA) or verapamil (240mg oid; VER) for 6 months and then the combination of the two drugs for additional 6 months. At baseline, 6 months and 12 months, peripheral microcirculation vasoreactivity was evaluated by forearm blood flow technique (venous plethysmography), as vasodilation to an endothelium-dependent (acetylcholine) and an endothelium-independent stimulus (sodium nitroprusside, SNP); minimal forearm vascular resistances (MFVR) were also evaluated. ResultsBlood pressure decreased similarly and progressively in both groups throughout the study period. In VER, 6-month verapamil treatment significantly increased vasodilation to acetylcholine, but not to SNP. The superimposition of trandolapril increased the response to SNP, and less to acetylcholine. In TRA group, 6-month treatment with trandolapril improved the response to SNP, but not to acetylcholine. In this group, the superimposition of verapamil caused a significant improvement in the response to acetylcholine, but not to SNP. At the end of the study, MFVR were significantly reduced in both groups, but to a greater extent in TRA. ConclusionThe present study demonstrates that chronic treatment with verapamil ameliorates endothelial function in the forearm microcirculation of essential hypertensive patients, while trandolapril protects microcirculation from structural alterations. The combination of the two drugs is potentially a powerful tool to counteract hypertension-related microvascular dysfunction and damage.

Chlorthalidone Improves Endothelial-Mediated Vascular Responses in Hypertension Complicated by Nondiabetic Metabolic Syndrome

The study was conducted to evaluate the vascular effects of chlorthalidone, a distal tubule-acting natriuretic agent, in hypertensive patients with nondiabetic metabolic syndrome, an insulin-resistant condition characterized by endothelial dysfunction and high risk for diabetes mellitus development. Thirteen untreated hypertensive patients with Adult Treatment Panel-III-defined nondiabetic metabolic syndrome were assigned to 3-month treatment with chlorthalidone. The end-points were baseline and post-treatment evaluation of (1) forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine infusion to test endothelial-mediated vasomotor function, with sodium nitroprusside as a control for endothelium-independent vasodilatation; (2) minimum forearm vascular resistance, the ratio of mean blood pressure and maximal blood flow in response to 13-minute arterial occlusion, as a hemodynamic correlate of arteriolar structure; and (3) transcapillary albumin escape rate (the 1-hour decay rate of (125)I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Additional measurements included baseline and posttreatment lipids, fasting, and postload glucose and insulin as well as the homeostasis model assessment, an index of insulin sensitivity. Chlorthalidone reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum forearm resistance, and slowed the transcapillary albumin escape rate. Metabolic parameters did not change significantly except for an increase in low-density lipoprotein cholesterol levels. Chlorthalidone improved endothelial function, reversed abnormal arteriolar structure, and slowed albumin permeation in hypertensive patients with nondiabetic metabolic syndrome.

Losartan but not atenolol reduce carotid artery hypertrophy in essential hypertension. A LIFE substudy

Background. We wanted to investigate whether treatment with losartan, an angiotensin II receptor blocker, induced regression of carotid artery hypertrophy as compared to the beta‐receptor blocker, atenolol. Methods. In 45 patients recruited for the LIFE Study with stage II‐III hypertension and ECG left ventricular (LV) hypertrophy, we measured blood pressure, intima‐media thickness (IMT) and lumen in the common carotid arteries by ultrasound, and minimal forearm vascular resistance (MFVR) by plethysmography, after 2 weeks of placebo treatment and after 1, 2 and 3 years of anti‐hypertensive treatment with either atenolol‐ or losartan‐based regimens. We measured the same parameters in 26 normal subjects matched for age and gender. Results. The patients had as compared to normotensive controls higher IMT (0.87 vs 0.76 mm, p = 0.001) and intima‐media cross‐sectional area (IMA) (19.7 vs 15.5 mm2, p<0.001). Systolic and diastolic blood pressures were reduced to the same degree in patients treated with losartan as compared to atenolol. However, IMA decreased significantly only in patients treated with losartan (19.2 vs 17.6 mm2, p = 0.001) and the average relative decrease in IMA during the 3 years of treatment was significantly higher in patients treated with losartan as compared to atenolol (−7.4 vs −2.0%, p<0.05). Conclusion. Patients with hypertension and LV hypertrophy had hypertrophy of the common carotid arteries. Losartan, but not atenolol, induced regression of this hypertrophy. Because carotid artery hypertrophy has been associated with strokes, our findings may explain the lower incidence of strokes in the LIFE study in patients treated with losartan as compared to atenolol.

Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction. In 70 hypertensive patients with electrocardiographic left ventricular hypertrophy, we measured minimal forearm vascular resistance (MFVR) by plethysmography and insulin sensitivity (M/IG) by a 2-h isoglycemic hyperinsulinemic clamp at baseline and after 1, 2 and 3 years of blinded treatment with atenolol- or losartan-based regimens. Blood pressures were reduced similarly in the two treatment groups. After 3 years, MFVR was increased (3.7 versus 3.2 mmHg x min x 100, P < 0.05) and M/IG decreased (8.6 versus 12.1 l/kg x mmol x min, P < 0.05) in patients treated with atenolol, whereas MFVR and M/IG were unchanged (3.5 versus 3.5 mmHg x min x 100 and 12.6 versus 11.1 l/kg x mmol x min, both P = NS) in patients treated with losartan. As compared to atenolol, losartan treatment was associated with less increase in MFVR (4.3 versus 27%, P < 0.05) and less decrease in M/IG (24 versus -14%, P < 0.01). The relative change in M/IG was inversely associated with the relative change in MFVR (r = -0.16, P < 0.05) independently of the relative change in body mass index (r = -0.29, P < 0.001). As compared to atenolol, losartan treatment was associated with less peripheral vascular hypertrophy/rarefaction and higher insulin sensitivity. The relative change in MFVR and M/IG were inversely related, supporting the hypothesis that peripheral vascular changes in hypertension may induce insulin resistance. The ability of losartan to preserve insulin sensitivity may explain the lower incidence of new onset diabetes in patients treated with losartan in the LIFE study.

The vascular effects of doxazosin in hypertension complicated by metabolic syndrome

To evaluate the vascular effects of doxazosin, an alpha-1 antagonist, in hypertensive patients with metabolic syndrome in whom the drug has previously been shown to exert beneficial metabolic actions on lipids and insulin metabolism. Twelve untreated non-diabetic hypertensive patients with National Cholesterol Education Program (NCEP) ATP-III defined metabolic syndrome were assigned to three-months of treatment with doxazosin (5.5 +/- 1.9 mg/die). Study variables were measured at baseline and after treatment. End-points: forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine and sodium nitroprusside infusion to test endothelium-dependent and independent vasodilatation respectively. Minimum forearm vascular resistance, the ratio of mean blood pressure and post-ischaemic maximal blood flow, as an index of arteriolar structure; transcapillary albumin escape rate (the 1-h decay rate of I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Lipids, fasting and post-glucose insulin were measured at baseline and after treatment. Doxazosin reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum resistance and, although not to a statistically significant extent, transvascular albumin leakage increased high-density lipoprotein (HDL) cholesterol while triglycerides and post-stimulative hyperinsulinemia decreased. Doxazosin improved endothelial-mediated vasomotor function and reversed abnormal arteriolar structure in hypertensive patients with metabolic syndrome while improving lipid profile and blunting post-glucose hyperinsulinemia.

Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P<0.05), MFVR(men) (r=0.35, P<0.01), 24-h systolic BP (r=0.24, P<0.05) and 24-h diastolic BP (r=0.22, P<0.05), but not to LV mass. After 1 year of treatment with reduction in systolic BP (175+/-15 vs 151+/-17 mmHg, P<0.001) and diastolic BP (99+/-8 vs 88+/-9 mmHg, P<0.001), ICTP was unchanged (3.7+/-1.4 vs 3.8+/-1.4 microg/l, NS) while PICP (121+/-39 vs 102+/-29 microg/l, P<0.001) decreased. The reduction in PICP/ICTP was related to the reduction in sitting diastolic BP (r=0.31, P<0.01) and regression of IMT (r=0.37, P<0.05) in patients receiving atenolol and to reduction in heart rate in patients receiving losartan (r=0.30, P<0.01). In conclusion, collagen markers reflecting net synthesis of type I collagen were positively related to vascular hypertrophy and BP load, suggesting that collagen synthesis in the vascular wall is increased in relation to high haemodynamic load in a reversible manner.

Is inappropriate left ventricular mass related to neurohormonal factors and/or arterial changes in hypertension? A LIFE substudy.

We investigated whether inappropriately high left ventricular (LV) mass, defined as observed LV mass exceeding the level of individual LV mass predicted from gender, height, and stroke work, may be associated with an imbalance between growth-promoting and growth-inhibitory factors and/or structural vascular changes. In 53 patients with hypertension and electrocardiographic LV hypertrophy, 24-h ambulatory blood pressure (BP); echocardiographic LV mass, stroke volume and stroke work; minimal forearm vascular resistance (MFVR); and intima-media cross-sectional area in common carotid arteries (IMA) were evaluated after 2 weeks of placebo treatment. Serum insulin, plasma epinephrine, norepinephrine, endothelin, angiotensin II, aldosterone, and brain natriuretic peptide (BNP) were also measured. High observed LV mass was related to high IMA (r=0.46, P<0.001), MFVR (in men: r=0.36, P<0.05), 24-h ambulatory systolic BP (r=0.30, P=0.06), and lower plasma angiotensin II (r=-0.33, P<0.05), but not to other circulating growth factors. Stroke work was similarly related to IMA (r=0.42, P<0.01), MFVR (in men: r=0.41, P<0.05), and plasma angiotensin II (r=-0.32, P<0.05). Inappropriate LV mass, identified by the ratio between observed LV mass and the value predicted for gender, height, and stroke work, was not significantly related to any of the arterial or neurohormonal variables. In this small series of older hypertensive patients, inappropriate LV mass was not significantly related to arterial changes or to measured circulating growth factors, although weak relations cannot be excluded. Alternatively, inappropriately high LV mass might be related to unmeasured factors such as local myocardial alterations in growth factors and/or genetic predisposition to develop excessive LV hypertrophy.

Association between vascular dysfunction and reduced myocardial flow reserve in patients with hypertension: a LIFE substudy.

Impaired myocardial flow reserve (MFR) has been demonstrated in hypertension, and has been associated with peripheral vascular changes. We investigated whether MFR was impaired and associated with structural and/or functional vascular changes in hypertensive patients without evidence of coronary artery disease (CAD). We measured left ventricular (LV) mass index by echocardiography and MFR by positron emission tomography in 33 unmedicated, hypertensive patients with electrocardiographic LV hypertrophy without CAD, and 15 age- and gender-matched normotensive subjects. We also measured 24-h ambulatory blood pressure, minimal forearm vascular resistance (MFVR) by plethysmography, media:lumen ratio in isolated, subcutaneous resistance arteries by myography, intima-media cross-sectional area of the common carotid artery, and flow-mediated (FMD) and nitroglycerin-induced dilatation (NID) of the brachial artery by ultrasound. Compared to the controls, the patients had impaired MFR (2.4 (95% CI 1.95-2.8) vs 3.4 (2.7-4.2), P<0.01) due to increased resting myocardial blood flow (MBF) (0.82 (0.73-0.91) vs 0.65 (0.56-0.75) ml/g min), and decreased dipyridamole-stimulated MBF (1.80 (1.55-2.1) vs 2.3 (1.80-2.8) ml/g min, both P<0.05). The difference in resting MBF disappeared (80 (74-87) vs 86 (74-97) microl/kg mmHg, NS) when normalized for blood pressure and heart rate. MFR correlated negatively to median 24-h systolic blood pressure (r=-0.50, P<0.01) as well as to LV mass index (r=-0.45, P<0.05) and MFVR in men (r=-0.47, P<0.05), and positively to FMD (r=0.44, P<0.05) and NID (r=0.40, P<0.05). Hypertensive patients with electrocardiographic LV hypertrophy without CAD had impaired MFR associated with cardiovascular hypertrophy and vasodilatory dysfunction. This suggests that MFR is impaired by LV hypertrophy and structural/functional vascular damage in the coronary and noncoronary circulation.

Ethnic differences in left ventricular structure: relations to hemodynamics and diurnal blood pressure variation

Background Previous studies have suggested that African Americans have a greater left ventricular relative wall thickness than whites with similar levels of blood pressure (BP), whereas other investigators have documented an attenuated nocturnal decline in BP and early remodeling of the resistance vessels in African Americans. Methods To further evaluate the contributions of diurnal BP variation and vascular remodeling to ethnic differences in left ventricular geometry, we measured ambulatory BP, systemic hemodynamics, minimum forearm vascular resistance, and left ventricular structure in a biracial sample of 171 men and women between the ages of 25 and 45 years. Results Despite similar resting BPs, African Americans had a greater indexed peripheral resistance, a greater minimal forearm vascular resistance, and a smaller nocturnal decline in BP than white subjects. African Americans also had a greater left ventricular relative wall thickness (0.41 ± 0.07 v 0.38 ± 0.08, P = .048) and a trend toward a greater indexed left ventricular mass (41.1 ± 8.7 v 38.6 ± 8.6 g/m 2.7, P = .087). Ethnic differences in relative wall thickness were no longer significant when adjusted for either indexed peripheral resistance ( P = .173) or sleep systolic BP ( P = .124). Conclusions In our cohort of young men and women, African Americans had a greater left ventricular relative wall thickness than whites with similar levels of resting BP. This early concentric remodeling of the left ventricle in African Americans may be mediated, in part, by hemodynamic influences, including a greater peripheral vascular resistance and a smaller nocturnal decline in BP.

Hypertension and Triglyceride Catabolism: Implications for the Hemodynamic Model of the Metabolic Syndrome

Objective: We sought to determine if hypertensive adults have a blunted triglyceride catabolic rate (TG K2) and if related hemodynamic and vascular alterations are determinants of TG K2.Methods: Fasting levels of insulin, glucose, lipoproteins and plasma catecholamines were measured in 10 normotensive and 10 hypertensive adults. TG K2 was determined by an intravenous fat tolerance test. Forearm blood flow, maximum forearm blood flow and minimal forearm vascular resistance were determined by strain gauge plethysmography. Vascular compliance and systemic hemodynamics were measured by computerized arterial pulse waveform analysis.Results: Compared to normotensives, hypertensives had a significantly elevated blood pressure (145 ± 8/94 ± 11 versus 111 ± 15/74 ± 14 mm Hg, p < 0.001), systemic vascular resistance (1695 ± 441 versus 1172 ± 430 dynes × sec × cm−5, p = 0.02) and reduced large vessel compliance (11.7 ± 3.6 versus 15.1 ± 3.1 ml/mm Hg × 100, p = 0.04). There were no significant group differences in TG K2 (3.07 ± 2.01 versus 2.88 ± 2.12 mg/dL/min, p = 0.85) or other metabolic and anthropometric variables. TG K2 was not predicted by the forearm vascular measures or the hemodynamic variables, but was correlated to waist/hip ratio (r = −0.71, p = 0.001), fasting triglycerides (r = −0.64, p = 0.003), and male gender (r = 0.56, p = 0.012). An enhanced TG K2 was independently predicted by a reduced small vessel compliance (r = −0.61, p = 0.006).Conclusions: Elevated blood pressure per se and hypertension-related hemodynamic and vascular alterations are not associated with reduced TG K2 or other metabolic abnormalities. Rather, aspects of the insulin resistance syndrome are closely related to abdominal adiposity. The independent association between small vessel compliance and TG K2 deserves further investigation.

Vasodilatory capacity and vascular structure in long-standing hypertension: a LIFE substudy

Background Flow-mediated dilatation (FMD), which is considered a measure of endothelial function, has been found impaired in hypertension. However, it is unclear whether this impairment is explained solely by endothelial dysfunction, or whether it is associated with structural vascular changes and reduced vasodilatory capacity. Methods In 42 unmedicated patients with hypertension and electrocardiographic left ventricular hypertrophy, we measured the following: 24-h ambulatory blood pressure (BP), minimal forearm vascular resistance (MFVR) by plethysmography, intima-media cross-sectional area of the common carotid arteries (IMA), FMD, and nitroglycerin-induced dilatation (NID) in the brachial artery by ultrasound. Results: We found that FMD was correlated positively with NID (r = 0.38, P < .05). However, FMD as well as NID correlated negatively to 24-h systolic BP (r = −0.41, P = .01 and r = −0.52, P = .001), IMA/height (r = −0.41, P < .01 and r = −0.53, P < .001) and MFVR men (r = −0.44, P < .05 and r = −0.42, P < .05). Conclusions Low FMD as well as low NID were related in parallel to high systolic BP and to the severity of vascular changes in different vascular beds, suggesting that elevated BP load in hypertension induces parallel abnormalities in conduit artery structure and overall vasodilatory capacity. Therefore, the decrease in FMD observed in severe hypertension may be caused by endothelial dysfunction as well as by structural vascular changes, suggesting difficulties in interpreting FMD solely as a measure of endothelial dysfunction in hypertensive patients with left ventricular hypertrophy.

Lower Plasma Noradrenaline and Blood Viscosity on Carvedilol vs Atenolol in Men with Recent Myocardial Infarction

The Carvedilol Acute Myocardial Infarction Study (CAMIS) investigates cardiac remodeling in patients ( n = 250) randomized to carvedilol vs atenolol and treated for 12 months after acute myocardial infarction. In a sub-study, we compared sympathetic, hemorrheological and vascular effects in small but particularly well-matched groups of participants who had been on reasonably equipotent but unchanged doses of carvedilol ( n = 10) or atenolol ( n = 10) for at least 4 weeks. Blood pressures ( p < 0.05), plasma adrenaline ( p = 0.034), plasma vasopressin ( p = 0.022) and whole blood viscosity at shear rate 0.5 cp ( p = 0.050), 1.1 cp ( p = 0.023), 5.8 cp ( p = 0.049) and 201 cp ( p = 0.060) taken in the laboratory at baseline before 2 h of using the hyperinsulinemic, isoglycemic glucose clamp were lower on carvedilol. Plasma noradrenaline was lower on carvedilol at baseline and throughout the clamp ( p < 0.0005). Forearm vascular resistance as measured by plethysmography during the clamp tended to be lower on carvedilol ( p = 0.074). No significant difference was found between the groups in glucose disposal rate measured by clamp, maximal forearm blood flow and minimal forearm vascular resistance after 10 min of ischemia, or in ambulatory blood pressure and heart rate taken a few days later. Thus, potential benefits of carvedilol vs atenolol were seen in these post-infarction patients in a laboratory setting. These findings suggest that the inhibitory effects on the sympathetic nervous system and related blood viscosity are stronger with carvedilol than with atenolol.

Maximal exercise capacity is related to cardiovascular structure in patients with longstanding hypertension. a LIFE substudy

Background Cardiovascular hypertrophy and remodeling in patients with never-treated hypertension has been associated with impaired exercise capacity, but whether this relationship remains in patients with longstanding hypertension and target organ damage is less elucidated. Methods: In 43 unmedicated patients with essential hypertension and electrocardiographic left ventricular (LV) hypertrophy, we measured maximal workload and oxygen reserve by bicycle test, 24-h ambulatory blood pressure (BP), LV mass index by magnetic resonance imaging (LVMI MRI, n = 31), LVMI echo and systemic vascular compliance by echocardiography, minimal forearm vascular resistance (MFVR) by plethysmography, and intima media thickness and distensibility in the common carotid arteries by ultrasound. Results The patients did not achieve the maximal workload as predicted by age, gender and body composition (146[129–163] v 162[146–179] Watt, P = .01). This impaired exercise capacity, calculated as the ratio between achieved and predicted maximal workload, was in simple regression analyses related to lower distensibility of the common carotid artery (r = 0.38, P = .01) and lower oxygen reserve (r = 0.68, P < .001). In multiple regression analyses, lower oxygen reserve was related to higher LVMI MRI (β = −0.44), lower systemic vascular compliance (β = −0.36), and higher MFVR (β = −0.52) (adjusted R 2 = 0.53, P < .001). Conclusions: Patients with longstanding hypertension and target organ damage cannot achieve the predicted maximal workload. This impaired exercise capacity was associated with lower common carotid distensibility and lower oxygen reserve. The latter was independently related to LV hypertrophy, low systemic vascular compliance and peripheral vascular remodeling, suggesting that cardiovascular hypertrophy and remodeling may reduce exercise capacity by itself.

Soluble e-selectin in essential hypertension: a correlate of vascular structural changes

Background: Increased expression of the endothelial leukocyte adhesion molecule E-selectin is implicated in vascular disease and may accompany the development of hypertension. We evaluated plasma soluble (s) E-selectin to assess its relationship with endothelium-dependent and endothelium-independent vasodilation in patients with hypertension. Methods: Thirty-one previously untreated and uncomplicated essential hypertensive patients were compared with 16 normotensive controls for changes in forearm blood flow (by strain-gauge plethysmography) in response to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine, and of the endothelium-independent vasodilator sodium nitroprusside. As an index of structural changes, minimal forearm vascular resistances were calculated as the ratio between maximal vasodilation after 13 min of ischemia and mean blood pressure. Results: Responses to acetylcholine were significantly lower and minimal forearm vascular resistances higher in hypertensives versus controls, whereas responses to nitroprusside were comparable. Baseline sE-selectin concentrations were (mean ± SEM) 37.4 ± 1.8 ng/mL in hypertensives and 27.8 ± 0.7 ng/mL in normotensives ( P < .001). In essential hypertensive patients, a significant ( P < .01) correlation with the response to nitroprusside (r = −0.47) was found, but not with the response to acetylcholine or minimal forearm vascular resistances. sE-selectin was also positively correlated with age and LDL cholesterol. At multivariate analysis, sE-selectin remained significantly correlated with nitroprusside responses and LDL cholesterol. Conclusions: In patients with essential hypertension, plasma levels of sE-selectin are higher than in normotensive controls and mostly related to structural vascular changes.

Vascular reactivity in patients with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome

Objective: Early structural and functional changes in the systemic vasculature have been proposed to play a major pathogenetic role in preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. The aim of the study was to determine vascular reactivity in patients with preeclampsia with and without HELLP syndrome with respect to those in healthy pregnant control subjects. Study Design: Forearm blood flow was measured by strain gauge plethysmography with the venous occlusion technique in 12 hypertensive patients with HELLP syndrome, in 8 patients with preeclampsia without HELLP syndrome, and in 8 healthy normotensive pregnant control subjects. To determine vascular reactivity the forearm blood flow was measured at baseline and after forearm occlusion for a period of 5 minutes (reactive hyperemia). The investigations were repeated 4 to 6 months post partum. Forearm vascular resistance was calculated as the ratio of mean arterial pressure to forearm blood flow. Results: Mean arterial pressure at rest was elevated in patients with preeclampsia (116 ± 20 mm Hg) and in patients with HELLP syndrome (110 ± 16 mm Hg) with respect to healthy pregnant control subjects (86 ± 10 mm Hg; P <.05). Forearm blood flow at rest was not statistically different in patients with preeclampsia (5.1 ± 2.6 mL/min per 100 mL) and with HELLP syndrome (4.7 ± 1.5 mL/min per 100 mL) with respect to pregnant control subjects (5.9 ± 3.1 mL/min per 100 mL); however, forearm vascular resistance at rest was elevated in patients with preeclampsia (25.9 ± 9.5 units; P <.05) and in patients with HELLP syndrome(24.6 ± 6.9 units; P <.05) with respect to healthy control subjects (17.0 ± 6.1 units). During reactive hyperemia the peak forearm blood flow, which is an indicator of maximal vasodilatory capacity, was impaired in patients with preeclampsia (21.9 ± 8.2 mL/min per 100 mL; P <.05) but not in patients with HELLP syndrome (37.4 ± 17.5 mL/min per 100 mL) and healthy control subjects (44.9 ± 15.0 mL/min per 100 mL). Consequently, minimum forearm vascular resistance was higher in women with preeclampsia (6.1 ± 1.9 units) than in both women with HELLP syndrome (3.5 ± 1.6 units) and the control subjects (2.8 ± 2.4 units). Conclusion: Despite similarly elevated forearm vascular resistances at rest in patients with HELLP syndrome and in patients with preeclampsia, forearm vascular resistance during reactive hyperemia did not differ significantly from that in healthy control subjects in the women with HELLP syndrome but was increased in women with preeclampsia. Vasodilatory reactivity thus is reduced in preeclampsia but not in HELLP syndrome, which suggests different alterations of the vasculature. (Am J Obstet Gynecol 2000;183:1489-94.)

Relative influence of insulin resistance versus blood pressure on vascular changes in longstanding hypertension. ICARUS, a LIFE sub study

Insulin resistance is associated with hypertension. The relative influences of hyperinsulinaemia and high blood pressure on vascular hypertrophy and carotid distensibility is unclear in patients with longstanding hypertension. In 88 unmedicated patients with stage II-III hypertension and left ventricular hypertrophy on electrocardiogram we measured blood pressure, minimal forearm vascular resistance (MFVR) using plethysmography, intima-media thickness (IMT) and the wall distensibility of the common carotid arteries using ultrasound, and insulin sensitivity using a 2-h isoglycaemic hyperinsulinaemic clamp. IMT was positively correlated to systolic blood pressure (r= 0.26, P < 0.05), whole body glucose uptake index (M/IG; r= 0.22, P< 0.05), age (r= 0.24, P< 0.05) and negatively correlated to body mass index (r= -0.24, P < 0.05); IMT did not correlate to fasting serum insulin (r= -0.14, NS). In men (n = 64) MFVR was positively correlated to systolic blood pressure (r = 0.30, P < 0.05), but was unrelated to M/G and serum insulin. The distensibility of the common carotid arteries was negatively correlated to systolic blood pressure (r = -0.40, P< 0.001) and in untreated patients (n = 22) positively correlated to M/IG (r = 0.47, P < 0.05). High systolic blood pressure was related to vascular hypertrophy, whereas hyperinsulinaemia and insulin resistance were not, suggesting that longstanding high blood pressure is a far more important determinant for structural vascular changes than insulin resistance at this stage of the hypertensive disease. However, hyperinsulinaemia and insulin resistance were associated with low distensibility of the common carotid arteries in the subgroup of never treated hypertensive patients.