Prevalence of carotid artery kinking in 590 consecutive subjects evaluated by Echocolordoppler. Is there a correlation with arterial hypertension?

OBJECTIVE: To assess a possible correlation between high blood pressure and prevalence of kinking in carotid arteries. DESIGN: Between July 1, 1997 and December 31, 1998, we evaluated the subjects submitted to Echocolordoppler examination of carotid arteries. SETTING: Patients were examined at the Laboratory for Noninvasive Vascular Diagnostics of the University Hospital in Verona. SUBJECTS: 590 consecutive subjects (M/F ratio, 1/1.2; mean age, 67 years; range, 36-86 years). MAIN OUTCOME MEASURES: An Echocolordoppler ultrasonograph to evaluate by means of the standard longitudinal and transverse scans the usual parameters of both intima-to-lumen interface and flow. Moreover, particular attention was paid to the analysis of the conformational characteristic of the vessels. Kinking has been classified in three classes according to the degree of bending. All the subjects were asked to compile a questionnaire that provided us with the clinical history. RESULTS: The prevalence of hypertension in the subjects with kinking appeared higher than in subjects without this abnormality (chi2 = 6.44, P < 0. 02). We found also a significant association between kinking and transitory ischaemic attacks (chi2 = 6.987, P < 0.01). CONCLUSIONS: The high prevalence of kinking in the hypertensives agrees with the pathogenetical hypothesis ascribing a role to the high endoluminal pressure. The presence of hypertension and kinking of the internal carotid artery suggests that they could be additive risk factors in the pathophysiology of a transitory ischaemic attack.

Prevalence of morphological alterations in cervical vessels: a colour duplex ultrasonographic study in a series of 3300 subjects.

BACKGROUND: In order to define the morphological variants involved in carotid elongation in terms of their clinical implications, we have analysed the prevalence of morphological alterations in patients routinely subjected to carotid colour duplex ultrasonography evaluation. METHODS: From January 1, 1993 to June 30, 1996, 3300 subjects were examined for central nervous system symptoms (41% of cases) or for screening related to ischaemic heart disease, lower limb arterial disease, hypertension or major dyslipidaemia (59% of cases). The chi(2)-test was used for statistical analysis. RESULTS: Morphological alterations increased with age. While kinking was more prevalent in females (female:male ratio 58% vs 42%), sharp kinking was significantly more frequent in males (39% vs 15%, p<0.001). Atheromatous plaques predominated in males (79% vs 46%, p<0.001), as well as cases with haemodynamically significant involvement (16% vs 7%, p<0.001). In patients with kinking there was a prevalence of haemodynamically significant lesions (chi(2)=52.7, p<0.001). A possible link between conformational abnormalities and hypertension appeared highly significant owing to a very different prevalence of high blood pressure in the group of subjects with kinking (chi(2)=239, p<0.001). We did not find a significant association between major neurological symptoms and the presence of kinking (chi(2)=0.215, p=0.643), but we found an association with transient ischaemic attacks (chi(2)=6.9, p<0.01). CONCLUSIONS: Conformational abnormalities like kinking, seem much more prevalent in subjects suffering from arterial hypertension. Even though high blood pressure is an important risk factor for transient ischaemic attacks, it is possible that the prevalence of atheromatous lesions and the flow turbulence linked to kinking may also play a role in their pathophysiology.

Postischemic hyperemia in subjects with lower limbs obstructive arteriopathy: role of PGI2 and endothelin.

The physiological basis of postischemic hyperemia is not yet fully understood. The present study investigated the effects of pharmacologic manipulation of the prostaglandin system on local hemodynamics. Strain-gauge plethysmography was used to study 8 normal subjects and 9 patients with obliterating arterial disease of the lower limbs. Hemodynamic evaluations were performed before treatment, after seven days of low-dose acetylsalicylic acid (100 mg/day) to inhibit platelet thromboxane synthesis, and after acute infusion of 1 g of acetylsalicylic acid to inhibit endothelial prostacyclin synthesis. In patients with arterial disease, the hemodynamic study was also carried out after infusion of iloprost, a synthetic prostacyclin analogue. Acute infusion of acetylsalicylic acid significantly reduced basal blood flow in normal subjects, but not in patients with arterial disease. In the latter group, iloprost affected neither basal nor maximal postischemic flow. The study also evaluated the role of endothelin in musculocutaneous hemodynamic regulation, both in physiological conditions and in atherosclerosis. This part of the study addressed the possibility that the hemodynamic effects of vasodilator prostanoids like prostacyclin might affect endothelin release in vivo. During reactive hyperemia, plasma endothelin was reduced in normal subjects (-1.02 pg/mL, 95% CI: -2.23, 0.08), but not in patients with atherosclerosis (-0.35 pg/mL, 95% CI: -1.45, 0.75). In both groups, plasma endothelin was not affected by aspirin. These findings confirm the role of prostacyclin in local hemodynamic regulation. In the normal subject, musculocutaneous blood flow seems to depend at least in part on the action of vasodilator prostanoids and endothelin. This is not the case in patients with arterial disease, in whom plasma endothelin does not seem to be affected by postischemic changes in blood flow. A possible explanation for this difference could be alteration of the endothelial function in patients with arterial disease, related to the functional and structural characteristics of the artery wall in atherosclerosis.

Changes in peripheral hemodynamics and vasodilating prostaglandins after high-dose short-term ibuprofen in chronically treated hypertensive patients.

The use of cyclooxygenase inhibitors has been seen to reduce the efficacy of many antihypertensive drugs. However, cyclooxygenase inhibitors are normally non-selective because they affect both vascular tissue, where the endothelial prostanoids exert principally a vasodilatory action, and the kidneys, where they also play an important role in regulating hydroelectrolytic metabolism by redistribution of intraparenchymal flow. To evaluate the relative importance of vascular district in the hypertensive patient, we administered ibuprofen - a drug acting with only a minimal antagonist activity. A group of 20 male hypertensives were randomly allocated, according to a single-blind protocol, to treatment with amlodipine (A, 10 mg/day) or lisinopril (L, 20 mg/day). Blood pressure was significantly reduced after 30 days, with a mean difference of -21.75 mmHg for systolic blood pressure (SBP) (95% confidence interval (Cl): -27.46 to -16.04; P< 0.0001) and -14.15 mmHg for diastolic blood pressure (DBP) (95% Cl: -17.13 to -11.17; P< 0.0001). Brachial artery compliance showed a mean increase of 1.657 x 10(-7) dyn-1 cm(4) (95% Cl: 1.188 to 2.126; P<0.001), and forearm resistances showed a mean decrease of -41.973 mmHg ml(-1)s (95% Cl: -75.479 to -8.467; P = 0.017). Changes in compliance were significantly related to those in SBP (r= -0.546; P= 0.013). The administration of ibuprofen (400 mg, three times a day for 3 days) was accompanied by a slight but significant increase in SBP, but not in brachial artery compliance or forearm resistances. Only SBP was affected, showing a mean increase of 4.25 mmHg (95% Cl: 1.26 to 7.24; P = 0.008). There was also reduced urinary excretion of PGI(2) and TXA(2) metabolites. The mean change in 6-keto-PGF(1 alpha) and 2,3-dinor-6-keto-PGF(1 alpha) was 45.71 ng per g urinary creatinine (uCr) (95% Cl: -0.16 to-91.25; P= 0.049) and -73.17 ng (g uCr)(-1) (95% Cl: -38.81 to -107.53; P<0.001), respectively. The mean decrease in TXA(2) catabolites was highly significant: -39.2 ng (g uCr)(-1) (95% Cl: -18.17 to-60.22; P< 0.001) and -102.87 ng (g uCr)(-1) (95% Cl: -61.86 to -143.88; P< 0.001) for TXB(2) and 2,3-dinor-TXB(2), respectively. Our study highlighted an inverse correlation between changes in blood pressure and those in urinary 2,3-dinor-6-keto-PGF(1alpha) excretion, irrespective of antihypertensive regimen. This suggests that, in the hypertensive patient treated with NSAIDs, inhibition of vascular prostanoid synthesis may play an important role in countering the efficacy of an important vascular tone regulatory mechanism.

Correlation between peripheral hemodynamic changes and left ventricular diastolic function in hypertensive patients treated with urapidil.

We evaluated the modifications induced by chronic treatment with an alpha 1-adrenolytic hybrid drug, urapidil, on the hemodynamic parameters in peripheral artery and left ventricle diastolic function. Fifteen mild to moderate essential hypertensive patients (13 men, 2 women; mean age 42 years, range 32-54 years) received urapidil (60 mg b.i.d.) for 6 months. Peripheral hemodynamic and cardiac parameters were evaluated by duplex scanner, coupled with a plethysmographic method, basally (T0) and after 6 weeks' (T1) and 6 months' treatment (T2). Mean blood pressure (BP) showed a reduction after 6 weeks of -9.07 mm Hg (confidence intervals [CI] 95%: -9.21; -8.92; P < 0.01), which was maintained after 6 months (-8.21 mm Hg, CI 95%: -8.97; -7.43; P < 0.01), while no significant change was seen in heart rate. Compliance showed highly significant changes after both 6 weeks (+1.073 dyn-1.cm4.10(-7), 95% CI: +0.965; +1.181, P < 0.001) and 6 months (+0.933 dyn-1.cm4. 10(-7), 95% CI: +0.903; +0.963, P < 0.001), as well as characteristic impedance (T1:-16.689 dyn.s.cm-5/10(2), 95% CI: -16.914; -16.463 P < 0.001; T2: -15.98 dyn.s.cm-5. 10(2), 95% CI: -18.186; -13.784; P < 0.001) and forearm resistances (T1: -26.153 mm Hg.ml-1.s, 95% CI: -34.553; -17.753, P < 0.01; T2: -43.587 mm Hg.ml-1.s, 95% CI: -52.711; -34.464, P < 0.01). Similarly, we have recorded a similar change in left ventricular end-diastolic posterior wall thickness (T1: -1.067 mm, 95% CI: -1.099; -1.035, P < 0.01; T2: -2.866 mm, 95% CI: -3.044; -2.688, P < 0.01), end-diastolic interventricular septum thickness (T1: -0.921 mm, 95% CI: -1.511; -0.289, P < 0.05; T2: -2.711 mm, 95% CI: -3.211; -2.199, P < 0.01), end-diastolic volume (T1: +6.4 ml, 95% CI: +6.343; +6.456, P < 0.01; T2: +19.867 ml, 95% CI: +18.564; +21.170, P < 0.01), and mass/volume index (T1: -0.11, 95% CI: -0.118; -0.101, P < 0.01; T2: -0.218, 95% CI: -0.221; -0.217, P < 0.01). Changes in arterial compliance have shown a statistically significant correlation with changes in mass/volume index (r = -0.468; P < 0.03), end diastolic volume (r = 0.501; P < 0.02), as well as left ventricle rapid filling phase (r = 0.426; P < 0.05) and left ventricle end diastolic posterior wall thickness (r = -0.478, P < 0.03). Our results suggest that the antihypertensive efficacy of urapidil coupled with the restoration of the dumping function of the large arteries, and the reduced activation of reflex sympathetic activation, may play a considerable role among the mechanisms allowing the regression of the functional modifications affecting the left ventricular diastole.

Amlodipine and haemodynamic effects of cyclo-oxygenase inhibition.

1. The haemodynamic effects of calcium antagonists could depend at least in part on the activity of vasoactive prostanoids. 2. We set out to study the effect of the cyclo-oxygenase inhibitor ibuprofen, 400 mg three times daily for 3 days, by a randomised cross-over study vs placebo in 12 mild to moderate essential hypertensive patients who had been treated for 1 month with amlodipine. 3. Blood pressure, heart rate and vascular resistances in the upper limb (Doppler ultrasound) were measured. Plasma renin activity and urinary aldosterone, as well as indices of renal function, were evaluated. Urinary 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2, as well as 6-keto-PGF1 alpha and TXB2, were measured as indices of systemic and renal PGI2 and TXA2 synthesis. 4. Amlodipine normalised blood pressure and reduced upper limb vascular resistances; it did not affect urinary prostanoid excretion. Short-term combined administration of ibuprofen resulted in, by comparison with placebo, inhibition of systemic PGI2 (-80.5 ng 24 h-1, 95% CI -99.2, -61.4; P < 0.001) and TXA2 (-216.1 ng 24 h-1, 95% CI -276.5, -155.8; P < 0.001), together with an increase in systolic (+7.8 mm Hg, 95% CI +3.1, +12.3; P < 0.01) and diastolic (+3.9 mm Hg, 95% CI +1.2, +6.6; P < 0.01) blood pressure; it had no significant effect on regional vascular resistances (+4.7 mm Hg ml-1 s, 95% CI -5.6, +15.0). Effects of ibuprofen on renal prostanoid synthesis were less marked, and there was no change in indices of renal function or hydro-electrolytic balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes induced by nicardipine slow release in forearm and myocardial hemodynamics of subjects with essential hypertension.

OBJECTIVE: To evaluate the modifications induced by chronic treatment with a new formulation of nicardipine (slow release) on the hemodynamic parameters in peripheral artery and left ventricle diastolic function. MATERIALS AND METHODS: Ten mild to moderate essential hypertensive male patients (mean age 42 years, range 32-54 years) received nicardipine slow release (40 mg b.i.d.) for six months. Peripheral hemodynamic and cardiac parameters were evaluated by duplex scanner, coupled with a plethysmographic method, basally (T0) and after 1 (T1) and 6 months' treatment (T2). RESULTS: Blood pressure showed a significant reduction after 1 month (mean blood pressure 109 +/- 2 vs 124 +/- 3 mmHg, M +/- SE, p < 0.001), which was maintained after 6 months (mean blood pressure 112 +/- 3 mmHg, p < 0.001), while heart rate showed only a slight, non-significant increase. There were highly significant changes in distensibility (0.29 +/- 0.02 vs 0.16 +/- 0.01 s2.cm-2, T2 vs T0, p < 0.001), characteristic impedance (55 +/- 3 vs 78 +/- 3 dyn.s.cm-5.10(2), T2 vs T0, p < 0.001) and local resistances (71 +/- 5 vs 118 +/- 4 mmHg.ml-1. s, T2 vs T0, p < 0.001) in the brachial artery, and also in left ventricle posterior wall diastolic thickness (10.2 +/- 0.4 vs 11.5 +/- 0.3 mm, T2 vs T0, p < 0.05), end diastolic volume (127 +/- 3 vs 109 +/- 3 ml, T2 vs T0, p < 0.01) and mass/volume index (1.21 +/- 0.03 vs 1.35 +/- 0.03, p < 0.05). CONCLUSIONS: The antihypertensive efficacy of nicardipine slow release, with only two daily administrations, allows the restoration of the dumping function of the large arteries, and the regression of the functional modifications affecting the left ventricular diastole.

Hemodynamic changes induced by cilazapril and atenolol during isometric stress in hypertensive patients.

We studied 16 mild to moderate essential hypertensive patients (14 male, 2 female; mean age 45 years, range 34-55 years) in order to investigate the effects of an ACE inhibitor, cilazapril (5 mg o.d.) and a selective beta-blocker, atenolol (100 mg o.d.) on the hemodynamics of the brachial and carotid arteries after an isometric stress test with a handgrip. Both drugs caused a statistically significant decrease in blood pressure after three months' treatment, but only cilazapril reduced it after the first dose. Heart rate was reduced only by atenolol (61 +/- 3 vs 71 +/- 3 bpm; p < 0.01). Changes in forearm compliance and characteristic impedance showed a difference statistically significant both for acute test and after three months of treatment. The increase in blood pressure during handgrip did not differ appreciably between the two treatment groups. On the contrary, after handgrip only cilazapril caused a significant increase of the reactive hyperemia.

Effects of sustained-release isradipine on blood pressure and peripheral hemodynamics in hypertensive patients.

In a double-blind crossover study, 16 hypertensive patients (mean age, 41 years) were randomly assigned to receive placebo or 5 mg of an extended-release formulation of isradipine for 30 days. Blood pressure and heart rate were recorded by an automatic device and hemodynamics measured by a duplex scanner and plethysmography. After the first dose and after 30 days' treatment with isradipine, blood pressure was significantly reduced (mean arterial pressure 4 hours after the first dose, 106 +/- 3 vs 120 +/- 4 mmHg, P < 0.01; 22 hours after the last dose, 108 +/- 3 mmHg, P < 0.01) with no significant changes in heart rate. The compliance of the brachial artery was significantly increased (2.823 +/- 0.358 vs 1.204 +/- 0.156 dyn-1.cm4.10(-7), P < 0.002) and the characteristic impedence decreased (49 +/- 6 vs 91 +/- 12 dyn.s.cm-5.10(2), P < 0.05) as well as local resistances (71 +/- 5.6 vs 198 +/- 18 mmHg.ml-1.s, P < 0.001). After 30 days of isradipine treatment, 22 hours after the last dose, compliance was still increased (2.575 +/- 0.453 dyn-1.cm4.10(-7), P < 0.01) whereas impedance and forearm vascular resistances were reduced (59 +/- 8 dyn.s.cm-5.10(2), P < 0.05, and 97 +/- 14 mmHg.ml-1.s, P < 0.001, respectively). The results indicate that sustained-release isradipine ensures good blood pressure control up to the time of the following dose and restores the large artery dumping function against cyclic variations in intraluminal pressure.

Changes in the haemodynamics of large arteries induced by single doses of nicardipine, enalapril, atenolol and urapidil.

Haemodynamic changes in the carotid and brachial arteries produced by single doses of four anti-hypertensive drugs (nicardipine, enalapril, atenolol, and urapidil) have been studied in 12 patients with essential hypertension. Measurements were performed noninvasively using a mechanographic method and B-mode pulsed Doppler ultrasonography. Within 7 h all of the drugs had caused a significant reduction in blood pressure, whereas heart rate showed a significant change only after atenolol. All the drugs produced a marked reduction in brachial pulse-wave velocity. Only nicardipine caused a significant reduction in vessel wall tension both in the carotid and brachial arteries, while brachial peripheral resistance was significantly reduced by all the drugs except atenolol. Neither atenolol nor enalapril caused any significant reduction in carotid peripheral resistance. The results show that all four antihypertensive drugs led to a beneficial increase in arterial compliance despite their different effects on peripheral resistance.