Baroreflex sensitivity and heredity in essential hypertension.

BACKGROUND. Abnormalities in baroreflex control of heart rate may be important in the pathogenesis of essential hypertension. METHODS AND RESULTS. To investigate the influence of heredity on baroreflex function, we measured baroreflex sensitivity in 40 untreated patients with essential hypertension grouped by the presence (FH+) or absence (FH-) of a family history of hypertension and in 24 normotensive counterparts. Baroreflex sensitivity was assessed by both high-pressure (phenylephrine bolus) and low-pressure (amyl nitrite inhalation) stimuli. Subject groups were matched for age, blood pressure, body weight, and race. Baroreflex sensitivity (in milliseconds per millimeter of mercury) assessed by amyl nitrite inhalation was 24.3 +/- 2.8 in FH- normotensives, 12.3 +/- 1.7 in FH+ normotensives, 15.4 +/- 3.3 in FH- hypertensives, and 8.1 +/- 1.2 in FH+ hypertensives. Baroreflex sensitivity assessed by phenylephrine bolus was 28.8 +/- 5.6 in FH- normotensives, 19.3 +/- 2.8 in FH+ normotensives, 19.1 +/- 2.0 in FH- hypertensives, and 13.6 +/- 1.3 in FH+ hypertensives. Two-factor analysis of variance showed significant effects on baroreflex sensitivity for blood pressure status (normotensive versus hypertensive) and for family history of hypertension. After control line (controlling) for the effects of several variables, including age, mean arterial pressure, body weight, and race through multiple linear regression analysis, the effect of family history of hypertension on baroreflex sensitivity was still highly significant. Indeed, of all variables investigated, family history of hypertension was the strongest unique baroreflex sensitivity predictor. CONCLUSIONS. These data suggest that the impairment in baroreflex sensitivity in hypertension is in part genetically determined and may be an important hereditary component in the pathogenesis of essential hypertension.     

A 2D Echo color-Doppler study of the extracranial carotid arteries in borderline arterial isolated systolic hypertension

BACKGROUND: The aim of this study was to evaluate the prevalence of atherosclerotic carotid lesions in isolated systolic borderline arterial hypertension by 2D echo color-Doppler and effect of night-time pressure fall by ambulatory blood pressure monitoring. METHODS: Outpatients from January 1992 to December 1998 were examined. One hundred and twenty normotensive control subjects and 99 isolated systolic borderline untreated hypertensives were studied, based on blood pressure fall were divided into dippers, with nocturnal systolic and/or diastolic blood pressure fall of >10%, and non dippers. Subjects with ischemic heart disease, valvulopathies, heart failure, renal insufficiency, cerebrovasculopathies, hypercholesterolemia (total cholesterol >200 mg/dl) and diabetes. Normotensives and hypertensives were homogenous for cardiovascular risk factors. A thickness of =/> 0.95 mm, calculated as a mean of 5 measurements of the common carotid artery, 2-3 cm from the carotid bifurcation, was considered a sign of myointimal thickening, and the plaque as a focal thickening of =/> 2 mm, based on echogenic characteristics and site. RESULTS: Compared to normotensives, isolated systolic borderline hypertensives, showed carotid arteries with an intima-media thickening (p=0.002) with one or more plaques (p=0.0001) much more frequently, while normal carotid arteries (p=0.0001) were less frequent. In normotensives, like in hypertensives, the prevalence of vasal lesions was not significantly different in dippers compared with non dippers. Plaques were most often localized at level of the common carotid and lesions were hard. CONCLUSIONS: The conclusions is drawn that isolated systolic hypertension is the sign of major vascular atherosclerotic lesions. The night-time pressure fall does not affect the importance of the lesions.     

Hyperinsulinemia,family history of hypertension,and essential hypertension

The aim of this study was the evaluation of the relationships among hyperinsulinemia, a family history of hypertension, and essential hypertension. Insulin and C-peptide responses to an oral glucose load were studied in 175 lean normotensives (N) and untreated hypertensives (H) with (F+) and without (F−) a family history of hypertension: 30 NF-, 30 NF+, 45 HF-, and 70 HF+. The groups were comparable for age, sex, body mass index, and blood pressure. The following parameters were evaluated: plasma glucose (G), serum insulin (I), and C-peptide (Cp) before and 30, 60, 90, and 120 min after the glucose load, fasting glucose/insulin ratio (ISI), fasting insulin/C-peptide ratio (I/Cp), and 24-h ambulatory blood pressure monitoring. Plasma glucose was measured, fasting and during the test, and it and I/Cp were similar in the four groups. Serum insulin and Cp, both fasting and stimulated, were significantly higher and ISI lower in normotensives and hypertensives with hypertensive parents. Grouping the subjects first on the basis of blood pressure and then on the basis of family history, no differences were found between normotensives and hypertensives, whereas I and Cp, fasting and stimulated, were significantly higher and ISI lower in subjects with positive as compared to negative family history. The closest correlations between insulin and ambulatory blood pressure were found in normotensives with hypertensive parents; in hypertensives with hypertensive parents we only found a direct correlation between fasting Cp and nocturnal blood pressure fall; in hypertensives with normotensive parents insulin inversely correlated with nocturnal blood pressure fall. Insulin resistance seems to have a familial basis, independently of the presence of hypertension. Instead of showing a causal relationship between insulin resistance and hypertension, our results indicate that the two are partly independent components of a common familial pattern.     

Increased circulating CD31+/CD42- microparticles are associated with impaired systemic artery elasticity in healthy subjects

BACKGROUND: Impaired artery elasticity has been found in various pathological conditions related to endothelial dysfunction. Recently, CD31+/CD42- microparticles (MPs) emerged as a marker of endothelial injury. Whether CD31+/CD42- MPs, generated under physiological conditions, are correlated with artery properties has not been reported. METHODS: We evaluated brachia-ankle pulse-wave velocity (baPWV) (n = 76) and C1 large-artery and C2 small-artery elasticity indices (n = 56), using noninvasive devices for pulse-wave analysis in a group of healthy persons. The number of circulating CD31+/CD427- MPs (n = 76) was measured by flow cytometric analysis. RESULTS: Circulating CD31+/CD42- MPs were positively correlated with values of baPWV (r = 0.371, P = .008) and with C1 large-artery and C2 small-artery elasticity indices (r = -0.294, P = .037; and r = -0.310, P = .027, respectively). Multivariate analysis identified CD31+/CD42- MPs as potent contributors to the development of impaired systemic artery elasticity. CONCLUSIONS: The level of circulating CD31+/CD42- MPs, an important biomarker of dysfunctional endothelium and vascular injury, is closely associated with impaired systemic artery elasticity in healthy subjects. The present study suggests that CD31+/CD42- MPs may be a novel surrogate marker for the clinical evaluation of vascular damage.     

Pulse wave velocity as an index of arterial stiffness: a comparison between newly diagnosed (untreated) hypertensive and normotensive middle-aged Malay men and its relationship with fasting insulin

BACKGROUND: Arterial stiffness, an aging process which is accelerated by hypertension, is emerging as a useful index of vascular health. There are evidences to suggest that hyperinsulinaemia may be an independent risk factor for coronary artery disease, besides its possible pathogenic role in essential hypertension. The main objectives of this study were to compare arterial stiffness between untreated hypertensives and normotensives and to investigate the relationship between fasting serum insulin and arterial stiffness. METHODS: A cross-sectional observational study was designed. Forty normotensive (median age 47 +/- 6 yrs.) and twenty untreated hypertensive Malay men (median age 50 +/- 7 yrs.) without clinical evidence of cardiovascular complications were selected. Pulse wave velocity measured using the automated Complior machine was used as an index of arterial stiffness. Other measurements obtained were blood pressure, body mass index, fasting insulin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, glucose and creatinine level. RESULTS: The blood pressure and pulse wave velocity (PWV) were significantly higher in the hypertensives compared to the normotensives (blood pressure 169/100 mm Hg +/- 14/7 vs. 120/80 mm Hg +/- 10/4, p < 0.001; PWV 11.69 m/s +/- 1.12 vs. 8.83 m/s +/- 1.35, p < 0.001). Other variables such as body mass index, fasting insulin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and haematocrit were comparable among the two groups. Within each group, there was a significant positive correlation between pulse wave velocity and systolic blood pressure (r = 0.76, p < 0.001 in normotensives; r = 0.73, p < 0.001 in hypertensives) and mean arterial pressure (r = 0.74, p < 0.001 in normotensives; r = 0.73, p < 0.001 in hypertensives). No correlation was noted between pulse wave velocity and diastolic blood pressure, age, body mass index, fasting insulin level, cholesterol, HDL-cholesterol, LDL-cholesterol or triglyceride levels. CONCLUSION: Arterial stiffness as determined by PWV is increased in newly diagnosed untreated hypertensive subjects even before clinically evident cardiovascular disease. However, arterial stiffness is not correlated with the fasting insulin level in normotensives and newly diagnosed hypertensives.     

Arterial properties of early hypertension.

In addition to high blood pressure, hypertension is characterised by metabolic and cardiovascular abnormalities, including decreased arterial compliance. To evaluate arterial involvement in early hypertension, we have employed a technique that analyses the arterial pulse wave contour to separately quantify proximal compliance (aorta and large arteries) and distal compliance (small arteries and arterioles). Proximal compliance was 24% lower in patients with borderline (diastolic BP 90-99 mmHg, n = 22) and 33% lower in patients with established (n = 19) hypertension than in normals (n = 15); distal compliance was 58% and 61% lower. These differences were not age-dependent, for in 27 age-matched pairs, proximal and distal compliances were 22% (P less than 0.01) and 55% (P less than 0.01) lower in hypertensives (diastolic BP greater than or equal to 95 mmHg) than in normotensives. Moreover, independent of BP or age, both proximal (P less than 0.05) and distal (P less than 0.01) compliance values were significantly lower in subjects with a family history of hypertension than in those without. Proximal compliance correlated inversely with indices of BP variability and heart work measured by automated whole-day blood pressure monitoring. Thus, changes in the elastic properties of the distal arterial circulation, reflected by decreased compliance, occur at the initiation of hypertension and may be an early diagnostic marker. Low proximal compliance appears to be associated with established hypertension, and might be a determinant of cardiovascular prognosis.     

Above-normal left ventricular systolic performance during exercise in young subjects with mild hypertension

Debate continues on whether left ventricular (LV) systolic functionduring exercise is abnormal in young subjects with mild hypertensionand on whether the abnormal blood pressure (BP) trend observedin hypertensives during prolonged exercise is due to impairedLV function. LV function was measured by means of M-mode echocardiographyduring prolonged exercise in 13 physically trained, young, mildhypertensives and 12 age-matched, trained normotensives withsimilar working capacity. Systolic BPIend-systolic volume (SBPIESV) and end-systolic stress/ESVat rest were greater in the hypertensives (P<0.0001 and P–0.034),while LV filling was impaired (P–0.05). BP clianges duringthe first 20 min of exercise were similar in the two groups,but thereafter the between-group BP difference tended to declineprogressively. LV diastolic dimension was similar at rest. Duringexercise it slightly increased in the normotensives and slightlydecreased in the hypertensives (P–0.032). Exercise ejectionfraction (P–0.018), SBPIESV (P<0.0001) and stress/ESV(P–0.027) were greater in the hypertensives throughoutthe test. SBPIESV normalized for LV wall thickness (P<0.0001)and the changes in SBPIESV from rest to exercise were also greaterin the hypertensives (P–0.002). Stroke volume increasedto a lower extent in the hypertensives, but the between-groupdifference was not statistically significant. The increase inSBPIESV from rest to exercise was related to the concentricremodelling of the ventricle in the hypertensives (P<0.0001)and the subjects grouped together (P<0.0001), but not inthe normotensives. In conclusion, increased LV systolic performance is presentearly in hypertension not only at rest but also during vigorousexercise. It is partly due to concentric remodelling of theleft ventricle and partly to enhanced inotropic state.     

Effects of aging and hypertension on the microcirculation

Alterations of structure and function of the microcirculation in hypertension in the elderly and changes with normotensive aging have not been fully clarified. We studied capillary pressure, density, and skin microvascular function in 46 subjects in 3 groups: elderly subjects (aged >60 years) with untreated hypertension (n=16), elderly normotensive subjects (n=16), and young normotensive subjects (age <45 years, n=14). In a subgroup of 19 subjects, we also studied resistance artery function in the isometric myograph. Capillary pressure was higher in both elderly groups (elderly hypertensives: 18.6+/-4.7 mm Hg, elderly normotensives: 17.6+/-4.0 mm Hg) compared with young normotensives (13.9+/-2.6 mm Hg, P<0.05), but capillary density did not differ between the groups. Skin vasodilating responses to acetylcholine were greater in young normotensives compared with both elderly groups (P<0.05). In isolated resistance arteries, there was a greater inhibitory effect from blockade of the l-arginine-NO pathway in elderly normotensives (P<0.05) and a reduction in the maximal inhibitory effect of combined blockade of NO, prostanoids, and endothelium-derived hyperpolarizing factor in elderly hypertensives (P<0.05). This study has demonstrated a significant effect of aging but no additional effect of hypertension on capillary pressure and no effect of either on capillary density. Our findings with both in vivo and in vitro methods suggest that normotensive aging may depend on relative preservation of NO-dependent vasodilatation in resistance arteries at the expense of a rise in capillary pressure.     

Susceptible and protective eNOS haplotypes in hypertensive black and white subjects

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been inconsistently associated with hypertension. This inconsistency may derive from population stratification secondary to ethnic diversity, and consideration limited to only one rather than combinations of polymorphisms. We studied three genetic variations in the eNOS gene: a single nucleotide polymorphism in the promoter region (T-786C), in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (b/a) of the eNOS gene in hypertensives (112 whites and 91 blacks) and normotensives (113 whites and 87 blacks). In addition, we also examined the association of eNOS gene haplotypes with hypertension in white and black subjects. No differences were observed in the frequencies of genotypes and alleles of the three polymorphisms when white hypertensives and white normotensives were compared, or when black hypertensives and black normotensives were compared (all P>0.05). Conversely, the haplotypes "T Asp b" and "C Glu b" were more common among white (16 and 24%, respectively) and black (17 and 16%, respectively) normotensives than in white (7 and 8%, respectively) and black (4 and 6%, respectively) hypertensives, respectively (all P<0.0039). In addition, the haplotype "C Asp b" was more commonly found in white hypertensives than in white normotensives (P=0.0007). These results suggest a contribution of eNOS haplotypes to the development of hypertension that is obscured when specific eNOS genotypes alone are considered. In addition, our results suggest two eNOS haplotypes associated with a protective effect against hypertension in both ethnic groups, and one eNOS haplotype conferring susceptibility to hypertension in white subjects.     

Ascending aortic blood pressure waveform is related to coronary atherosclerosis in hypertensive as well as in normotensive subjects

Ascending aortic blood pressure-derived indices were shown to be related to coronary atherosclerosis. However, no study so far has analyzed the relation between ascending aortic pulsatility and the extent of coronary atherosclerosis in normotensives. Therefore, the aim of the present analysis was to assess the relation between central blood pressure-derived indices and the presence and extent of coronary artery disease in patients with and without hypertension. The study group consisted of 821 patients (590 men and 231 women; mean age: 57.3 +/- 10.0 years) with preserved left ventricular function (ejection fraction>50%) undergoing coronary angiography. Hypertension was diagnosed in 639 (77.8%) patients. Ascending aortic blood pressure during catheterization was measured. After multivariate stepwise adjustment the odds ratio (OR) and confidence interval (CI) of coronary artery disease was: pulsatility per standard deviation (SD) OR 1.36 (95% CI 1.01-1.82) in hypertensives and OR 3.96 (1.95-8.07) in normotensives; pulsatility index per SD OR 1.36 (95% CI 1.01-1.85) in hypertensives and OR 4.41 (2.03-9.56) in normotensives. Stepwise linear regression analysis revealed that pulsatility is related to the mean stenosis in the coronary tree in hypertensives (beta = 0.0862, SE = 0.0448, p<0.05) as well as in normotensives (beta = 0.1704, SE = 0.0718, p<0.05). In conclusion, ascending aortic pulsatility is related to the extent of coronary atherosclerosis irrespectively of the presence of hypertension.     

Salt taste perception and relationship with blood pressure in type 2 diabetics

Patients with type 2 diabetes (normotensives, n=59; hypertensives, n=56) and matched controls (n=60) had salt taste perception determined using graded NaCl solutions ( 0-400 mmol 1(-1)). Diabetic hypertensives, diabetic normotensives and controls differed significantly in taste threshold to NaCl recognition (F=4.4, P=0.01) and prevalence of NaCl taste insensitivity (P=0.003). Taste threshold to NaCl recognition correlated positively with duration of diabetes (r=0.402, P=0.04) and was associated with mean arterial pressure (P<0.001), the association being significant after adjustment for age (P<0.001), gender (P< 0.001), family history of hypertension ( P< 001), body mass index (P<0.01), antihypertensive medication ( P<0.01) and proteinuria ( P<0.04).     

Safety and feasibility of dobutamine and dipyridamole stress echocardiography in hypertensive patients

OBJECTIVES : To establish whether safety and feasibility of dobutamine and dipyridamole stress echocardiography are affected by history of hypertension. METHODS : Data on 2200 consecutive pharmacologic stress echocardiography (959 dobutamine and 1241 dipyridamole) performed between October 1990 and February 2001 at a single cardiology centre, were analysed. RESULTS : There were two complications (1/480 tests) during dobutamine (one sustained ventricular tachycardia and one severe asthmatic attack following antidote administration) and two (1/620 tests) during dipyridamole (one non-Q wave myocardial infarction and one sustained ventricular tachycardia) stress. Complications or limiting side effects were observed in 83/959 patients (48/430 hypertensives and 35/529 normotensives) with dobutamine and in 34/1241 patients (17/571 hypertensives and 17/670 normotensives) with dipyridamole stress. Therefore, the overall feasibility was 88.8% in hypertensives and 93.4% in normotensives (P = 0.013) for dobutamine, and 97% in hypertensives and 97.5% in normotensives (P = 0.64) for dipyridamole. Dipyridamole was significantly more feasible than dobutamine in both hypertensive (P < 0.0001) and normotensive (P = 0.0006) subjects. Logistic regression analysis failed to identify clinical or echocardiographic predictors of adverse reactions with dipyridamole, while history of hypertension [odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.1-2.8, P = 0.0138] was the only independent predictor of cumulative adverse reactions with dobutamine stress. In addition, history of hypertension (OR = 3.2, 95% CI, 1.2-8.5, P = 0.0166), resting wall motion abnormalities (OR = 1.8, 95% CI, 1.1-3.1, P = 0.0282), and age over 70 years (OR = 4.8, 95% CI, 1.5-15.3, P = 0.0087) predicted hypertensive response, ventricular tachycardia, and atrial fibrillation, respectively. No covariate was associated with hypotensive response during dobutamine test. CONCLUSIONS : Dipyridamole has a slightly better safety profile and significantly higher feasibility than dobutamine stress both in hypertensives and in normotensives. In addition, the history of systemic hypertension is an independent predictor of cumulative adverse effects during dobutamine but not during dipyridamole stress.     

Sleep-disordered breathing and hypertension among African Americans

This study investigated differences in sleep-disordered breathing (SDB) between hypertensives without a family history of hypertension and hypertensives with a family history. Furthermore, it examined whether these two groups differed in the severity of SDB. Patients were African Americans (n=162, mean age=51.19+/-13.77 years; mean body mass index (BMI)=37.85+/-9.51 kg/m2, male=57%), who were referred to the clinic because of a sleep complaint. Sleep was recorded in the laboratory using standard physiological parameters; all parameters were analysed by a trained scorer. Altogether, 91% of the patients received an SDB diagnosis. Of these patients, 25% were hypertensives without a family history, 20% were hypertensives with a family history, and 55% were normotensives. We found a significant difference between these patient groups regarding the severity of SDB (F14,158=1.823, P<0.05), but no significant group difference was observed in the rate of SDB. Increasing weight was accompanied by increasing severity of SDB. The finding that hypertensive patients with or without a positive family history showed worse oxygenation and respiratory characteristics than did normotensives is consistent with previous research. Of note, hypertensives reporting a family history were characterized by a greater number of oxygen desaturations and apnoea hypopnoea index than those typified only by a current diagnosis of hypertension. Hypertensives with a family history are likely to show a profile of greater blood pressure, higher BMI, and more severe SDB, which by all accounts are more common among African Americans.     

Relationship between small-artery structure and systolic, diastolic and pulse pressure in essential hypertension

OBJECTIVE: Studies of cerebral arterioles have suggested that pulse pressure may be a more important determinant of small-artery structure than systolic, diastolic or mean blood pressure in stroke-prone spontaneously hypertensive rats and in rats with an arterio-venous shunt. A study of small arteries has suggested that this is not the case in human essential hypertension. We therefore investigated the role of hemodynamic determinants on small-artery structure in hypertensive patients. DESIGN AND METHODS: To determine whether pulse pressure contributes to structural alterations in human essential hypertension, small arteries (lumen < 300 microns) were obtained from gluteal subcutaneous biopsies of 40 normotensive subjects aged 40.7 +/- 1.2 years and 45 untreated essential hypertensive humans aged 46.5 +/- 1.3 years. The relationship between the media: lumen ratio of the small arteries and levels of systolic, diastolic and mean blood pressure and pulse pressure was investigated. RESULTS: The media: lumen ratio (5.33 +/- 0.001%) of small gluteal subcutaneous arteries of normotensive subjects was significantly smaller and the lumen diameter (306 +/- 13 microns) significantly larger than in untreated hypertensive patients (7.42 +/- 0.001% and 244 +/- 9.7 microns respectively, P < 0.001). The media: lumen ratio of both groups examined together correlated with systolic blood pressure (r = 0.45, P < 0.001), diastolic blood pressure (r = 0.56, P < 0.001) and mean arterial pressure (r = 0.55, P < 0.001). The media: lumen ratio of vessels from hypertensive patients correlated with diastolic blood pressure (r = 0.22, P < 0.01) but not with systolic or mean blood pressure. There was no correlation between the media: lumen ratio of small gluteal subcutaneous arteries and pulse pressure in this population of normotensive and hypertensive subjects, examined together or separately. CONCLUSION: These results suggest that in 30- to 65-year-old humans with systolodiastolic essential hypertension, pulse pressure does not appear to be an important determinant of small-artery structure.     

Platelet Na(+)-H+ exchanger activity in normotensive and hypertensive subjects: effect of enalapril therapy upon antiport activity.

OBJECTIVE: Primary hypertension has been reported to be associated with an enhancement of Na(+)-H+ exchange. However, details of the kinetic properties of the Na(+)-H+ exchanger in hypertensives and its dependence upon age and gender in normotensives are unknown. PARTICIPANTS: We determined the activity of the platelet Na(+)-H+ exchanger in 20 normotensives and 26 untreated primary hypertensives. INTERVENTIONS: In eight hypertensive individuals antihypertensive treatment was interrupted for 1 week. Treatment for 6 weeks with a daily single dose of 10 mg enalapril decreased mean arterial pressure to 105.7 +/- 11.6 mmHg. METHODS: Platelets were loaded with the intracellular pH (pHi) indicator 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein (BCECF) and acidified by propionic acid. Initial velocities of pH recovery were determined and used for calculation of maximum velocity (Vmax), baseline pHi and the pHi value for half maximal activation (pH0.5) of the Na(+)-H+ exchanger in each individual. RESULTS: In normotensives, Vmax averaged 0.05 +/- 0.01 dpHi/min independently of age, gender and actual diastolic blood pressure. In hypertensives, two different subgroups were defined bearing either low or high Na(+)-H+ exchange activity. Values of pHi and pH0.5 were identical in all subgroups irrespective of Vmax. The twofold enhancement of Na(+)-H+ exchange in the second group was preserved in thrombin-stimulated platelets. Vmax values remained unaffected by enalapril treatment. CONCLUSIONS: Enhanced Na(+)-H+ exchange activity in hypertensives is primarily characterized by an increase in Vmax. This enhancement is refractory to antihypertensive treatment and therefore appears to be a relatively fixed parameter.     

Impact of arterial elastance as a measure of vascular load on left ventricular geometry in hypertension.

OBJECTIVE: Effective arterial elastance (Ea), integrating the pulsatile component of left ventricular (LV) afterload, is an estimate of aortic input impedance. We evaluated relationships of Ea with left ventricular anatomy and function in essential hypertension. DESIGN: A cross-sectional analysis in 81 normotensive and 174 untreated hypertensive individuals enrolled in a referral hypertension centre. METHODS: Using echocardiography we determined left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume (SV), endocardial (FSe) and midwall (FSm) fractional shortening and total peripheral resistance (TPR). Carotid pressure waveforms were obtained by arterial tonometry, and end-systolic pressure (Pes) was measured at the dicrotic notch. Ea index (EaI) was calculated as Pes/(SV index); LV elastance (Ees) was estimated as Pes/LV end-systolic volume, and ventriculo-arterial coupling was evaluated by the Ea/Ees ratio. RESULTS: EaI was higher in hypertensives than in normotensives (3.02 +/- 0.63 versus 2.40 +/- 0.52 mmHg/l per m2; P< 0.0001). Using the 95% upper confidence limit in normotensives, hypertensives were divided in two groups with normal or elevated EaI. The 38 hypertensives with elevated EaI had higher RWT (0.41 +/- 0.06 versus 0.37 +/- 0.05), lower LVMI (87.5 +/- 18.5 versus 96.8 +/- 19.3 g/m2), higher TPR (2247 +/- 408 versus 1658 +/- 371 dynes/cm s(-5)) and lower FSe and FSm (35 +/- 5 versus 39 +/- 5 and 16 +/- 2 versus 18 +/- 2%; all P< 0.05) than patients with normal EaI. Ea/Ees ratio was increased and cardiac output was reduced in hypertensives with elevated EaI. CONCLUSIONS: High values of EaI identify a minority of hypertensive patients characterized by elevated TPR, left ventricular concentric remodelling, depressed left ventricular systolic function and impaired ventriculo-arterial coupling.     

Association of serum bilirubin with pulsatile arterial function in asymptomatic young adults: the Bogalusa Heart Study

The inverse association between serum bilirubin, a potent antioxidant, and oxidative stress-mediated diseases like cardiovascular disease is known. However, information is scant regarding the influence of bilirubin in relation to traditional cardiovascular risk factors on pulsatile arterial function in asymptomatic younger adults. The present study examines this aspect in 777 black and white subjects (71% white, 42% male) aged 18 to 44 years. Pulsatile arterial function was assessed in terms of large-artery (capacitive) and small-artery (oscillatory) compliances by radial artery pressure pulse contour analysis. In bivariate analysis adjusted for race and sex, bilirubin related significantly and positively to large- and small-artery compliances and high-density lipoprotein cholesterol, and inversely to age, body mass index, blood pressure variables, non-high-density lipoprotein cholesterol, triglycerides, and insulin resistance index. In multivariable analysis including race, sex, body surface area, and risk factor variables mentioned above, bilirubin did not relate to large-artery compliance, without or with smoking status in the model, whereas bilirubin associated beneficially with small-artery compliance (P=.01) in a model that excluded smoking status. When smoking status was included in the model, this association became less strong (P=.04); and smoking entered the model as an adverse predictor (P=.003). The observed beneficial association of serum bilirubin on pulsatile arterial function, albeit the attenuating effect of smoking on this relationship, in asymptomatic younger adults supports the antioxidant function of bilirubin in providing protection against oxidative stress-mediated vascular dysfunction.     

Natriuretic hormones in young hypertensives and in young normotensives with or without a family history of hypertension.

The behavior of plasma atrial natriuretic factor (ANF) and digoxin-like substance (DLS), and the daily urinary excretion of kallikrein (uKK) were evaluated in young hypertensives and in young normotensives with or without a family history of essential hypertension. Each group was also evaluated, separating those with low plasma renin activity from the total sample. The sample group was made up of 75 young males; 31 hypertensives (mean age 22.7 +/- 2.5 years), 28 normotensives with hypertensive heredity (normotensives F+) (mean age 22.2 +/- 1.9 years) and 16 normotensives (mean age 22.0 +/- 2.1 years). An inverse correlation between ANF and PRA was shown in all groups. In hypertensives, ANF was inversely correlated with uKK (r = -0.664, P less than .0001). Plasma ANF (P less than .012) and DLS (P less than .0001) were higher in hypertensives than in normotensives, while uKK excretion was lower (P less than .0001). Plasma levels of DLS were higher in F+ normotensives than in normotensives (P less than .003). Low renin hypertensives showed the lowest uKK excretion (P less than .0001 v normal-high renin hypertensives). Furthermore, low renin hypertensives showed the highest plasma levels of ANF (P less than .0001 v normal high renin hypertensives) and DLS (P less than .012 v normal-high renin hypertensives). Plasma ANF (P less than .0001) was higher, while uKK was lower (P less than .045) in low renin F+ normotensives than in normal-high renin ones. In conclusion, our data indicate that plasma ANF and DLS are elevated since the early phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood pressure normalization is associated with normal left ventricular mass but not carotid geometry: the ICARe Dicomano Study

OBJECTIVE: While many studies have examined the relation between antihypertensive treatment and ventricular hypertrophy, relatively few data are available regarding changes in arterial structure due to blood pressure reduction. Therefore, we compared normotensive to untreated hypertensive subjects to uncontrolled (treated with elevated blood pressure values) or controlled (treated with normal blood pressure values) hypertensive older subjects. PATIENTS: Community-dwellers (age >or= 65 years) of a small town in Italy (Dicomano) underwent extensive clinical examination, echocardiography, carotid ultrasonography, and applanation tonometry. Of the 614 participants, 173 subjects were normotensive; among the hypertensive subjects, 225 were untreated (51%), 177 (40%) were uncontrolled, and only 39 (9%) were controlled. RESULTS: The majority of treated hypertensive subjects were on monotherapy (82%). Subjects with a history of coronary artery disease or stroke were more frequently treated. Controlled hypertensives had left ventricular mass index similar to normotensives but lower than uncontrolled and untreated hypertensives. There were no differences among the three hypertensive groups in carotid artery structure. Only the pressure-independent stiffness index was reduced in the treated hypertensive subjects compared to untreated hypertensives, with no difference between controlled and uncontrolled subjects. CONCLUSIONS: In our community-based, older population, antihypertensive treatment was associated with a normal left ventricular mass only when blood pressure was well controlled. In contrast, carotid artery remodeling and atherosclerosis were independent of antihypertensive treatment as well as of achievement of satisfactory blood pressure control. However, antihypertensive treatment was associated with significantly higher carotid compliance even in the absence of detectable changes in carotid structure.     

Persistent remodeling of resistance arteries in type 2 diabetic patients on antihypertensive treatment

We hypothesized that resistance arteries from diabetic patients with controlled hypertension have less remodeling than vessels from untreated hypertensive subjects. Eight normotensive subjects (aged 44+/-3 years, 3 men; values are mean+/-SEM), 19 untreated hypertensive subjects (46+/-2 years, 9 men), and 23 hypertensive subjects with type 2 diabetes mellitus under antihypertensive treatment (58+/-1 years, 15 men) were studied. Resistance arteries dissected from gluteal subcutaneous tissue were assessed on a pressurized myograph. Most diabetic patients (70%) were being treated with angiotensin-converting enzyme inhibitors. Although systolic blood pressure was still above the normotensive range in these patients (144+/-2 versus 150+/-3 mm Hg in hypertensive and 114+/-4 mm Hg in normotensive subjects), diastolic blood pressure was well controlled (83+/-2 mm Hg) and significantly lower compared with that in untreated hypertensives (100+/-1 mm Hg; P<0.001) but higher than in normotensives (76+/-3 mm Hg; P<0.05). Thus, pulse pressure was higher in diabetic patients (P<0.05). The media-to-lumen ratio of resistance arteries was greater in hypertensives (0.083+/-0.002) compared with normotensive controls (0.059+/-0.003; P<0.05) and was even higher in diabetic hypertensive subjects (0.105+/-0.004; P<0.001 versus normotensive controls). The medial cross-sectional area was greater in diabetic and hypertensive patients compared with normotensive controls (P<0.001). Acetylcholine-induced relaxation was impaired in vessels from hypertensive patients and from patients with both diabetes mellitus and hypertension (P<0.05 versus normotensive controls), whereas endothelium-independent vasorelaxation was similar in all groups. Despite effective antihypertensive treatment, resistance arteries from hypertensive diabetic patients showed marked remodeling, greater than that of vessels from untreated, nondiabetic, hypertensive subjects, in agreement with the high cardiovascular risk of subjects suffering from both diabetes and hypertension.