Associations between common carotid artery diameter, Framingham risk score and cardiovascular events.

BACKGROUND AND AIMS: Vascular biomarkers are associated with risk burden and are capable to predict the development of future cardiovascular (CV) events; yet, their additive predictive value over and above established risk algorithms seems to be only modest. The present study evaluated the cross-sectional associations between vascular biomarkers, 10-year Framingham risk (FR) and prevalent CV events in a population with a high prevalence of hypertension and diabetes. METHODS AND RESULTS: As many as 681 subjects (419 men, age = 60 ± 10 years, 282 diabetics, 335 hypertensives, mean FR score = 22.5 ± 16.5%) underwent an integrated vascular examination including: radiofrequency-based ultrasound of common carotid artery (cca) to measure intima-media thickness (IMT), inter-adventitial diameter (IAD) and local pulse wave velocity (PWV); applanation tonometry to assess carotid pulse pressure (PP) and augmentation index (AIx); carotid-femoral PWV (cfPWV) measurement. One hundred and thirty-five subjects (19.8%) had history of CV events, and CV events were independently associated with male sex, age, antihypertensive treatment, current smoking, HDL-cholesterol and ccaIAD. In logistic regression model, only ccaIAD was associated with prevalence of CV events after adjustment for FR score, with the OR of 1.71 [1.34-2.19] (P < 0.0001) that remained unchanged when ccaIMT was included into the model (OR = 1.76 [1.36-2.27]; P < 0.0001). The association between prevalent CV events and ccaIAD was significant (OR of 1.65 [1.24-2.20]; P = 0.0005) also in a subgroup of subjects being at a high 10-year risk of CV disease (N = 330). CONCLUSIONS: In a population with a high prevalence of diabetes and hypertension, ccaIAD was the only vascular measure associated with prevalent CV events, independently of FR score.

Hemodynamic overload and intra-abdominal adiposity in obese children: Relationships with cardiovascular structure and function.

BACKGROUND AND AIMS: Childhood obesity promotes adverse changes in cardiovascular structure and function. This study evaluated whether these changes are related to intra-abdominal adiposity and associated cardiometabolic risk or to body-size induced hemodynamic overload. METHODS AND RESULTS: 55 obese children/adolescents and 35 healthy-weight controls underwent carotid, cardiac and abdominal ultrasound to assess carotid artery intima-media thickness (IMT), diameter, distension and stiffness, left ventricular (LV) dimension, mass and function and extent of intra-abdominal adiposity. As compared to controls with healthy BMI, obese children had higher systolic blood pressure (BP), stroke volume and lower total peripheral resistance (P < 0.001-0.0001), higher plasma triglycerides, glycated hemoglobin, insulin and HOMA-IR index (P = 0.01-<0.0001), higher carotid IMT, diameter and distension (P < 0.005-0.0005), higher LV diameter, wall thickness and mass (P < 0.001-0.0001), and impaired LV diastolic function assessed by myocardial longitudinal performance (P < 0.005). In entire population, independent determinants of carotid diameter, LV diameter, wall thickness and mass were fat-free mass (or stroke volume, respectively) and BP. Carotid distension was determined by carotid diameter and BP, and carotid IMT by carotid diameter, BP, HDL-cholesterol and glycated hemoglobin. LV diastolic performance was inversely related to preperitoneal fat thickness and plasma insulin levels. CONCLUSIONS: Obese youths present signs of impaired lipid and glucose metabolism, hyperdynamic circulation and cardiovascular changes. Increase in LV dimensions and mass and in carotid diameter and distension seems to reflect adaptation to body-size induced increase in hemodynamic load, changes in LV diastolic performance a negative impact of intra-abdominal adiposity and associated metabolic risk, and increase in IMT both adaptive remodeling and metabolic risk.

Measures of atherosclerotic burden are associated with clinically manifest cardiovascular disease in type 2 diabetes: a European cross-sectional study.

BACKGROUND: There is a need to develop and validate surrogate markers of cardiovascular disease (CVD) in subjects with diabetes. The macrovascular changes associated with diabetes include aggravated atherosclerosis, increased arterial stiffness and endothelial dysfunction. The aim of this study was to determine which of these factors is most strongly associated with clinically manifest cardiovascular events. METHODS: Vascular changes were measured in a cohort of 458 subjects with type 2 diabetes (T2D) and CVD (myocardial infarction, stroke or lower extremity arterial disease), 527 subjects with T2D but without clinically manifest CVD and 515 subjects without T2D and with or without CVD. RESULTS: Carotid intima-media thickness (IMT) and ankle-brachial pressure index were independently associated with the presence of CVD in subjects with T2D, whereas pulse wave velocity and endothelial function provided limited independent additive information. Measurement of IMT in the carotid bulb provided better discrimination of the presence of CVD in subjects with T2D than measurement of IMT in the common carotid artery. The factors most significantly associated with increased carotid IMT in T2D were age, disease duration, systolic blood pressure, impaired renal function and increased arterial stiffness, whereas there were no or weak independent associations with metabolic factors and endothelial dysfunction. CONCLUSIONS: Measures of atherosclerotic burden are associated with clinically manifest CVD in subjects with T2D. In addition, vascular changes that are not directly related to known metabolic risk factors are important in the development of both atherosclerosis and CVD in T2D. A better understanding of the mechanisms involved is crucial for enabling better identification of CVD risk in T2D.

Gender-specific differences in carotid intima-media thickness and its progression over three years: a multicenter European study.

BACKGROUND AND AIMS: This multicentre European study evaluated, in a young-to-middle-aged healthy population without carotid atherosclerosis, the gender-related differences in carotid intima-media thickness (IMT) and its short-term (3-year) progression, and whether these differences are related to different vascular ageing rate, cardiovascular risk profile or different susceptibility to family predisposition to cardiovascular diseases (CVD). METHODS AND RESULTS: 366 men and 422 women (age between 30 and 60 years) underwent B-mode carotid ultrasound at baseline and after 3-year follow-up period. IMT in 3 carotid segments was higher in men than in women (p < 0.0001 for all segments). When evaluated according to age decade, differences between men and women disappeared in the 6th decade, as in this decade a 3-year IMT progression rate accelerated in women (p < 0.05 as compared to the 4th and 5th age decade). Age was a major determinant of baseline all-segment IMT in women; in men all-segment IMT was influenced by age and LDL-cholesterol. IMT progression did not correlate with established cardiovascular risk factors, their short-term changes or family predisposition to CVD. Yet, a 3-year IMT progression in common carotid artery (CCA) was higher in men (p = 0.01) and women (p < 0.01) in whom relative Framingham risk increased during the corresponding period. CONCLUSION: This study provides reference values on IMT and its short-term progression in healthy young-to-middle-aged population, and demonstrates gender-related differences in the susceptibility of carotid wall to ageing and LDL-cholesterol. Increase in Framingham risk accelerated a short-term CCA IMT progression rate in both genders, whereas family predisposition to CVD did not influence carotid IMT.

Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.

Insulin-mediated vasodilation has been proposed as a determinant of in vivo insulin sensitivity. We tested whether sustained vasodilation with adenosine could overcome the muscle insulin resistance present in mildly overweight patients with essential hypertension. Using the forearm technique, we measured the response to a 40-min local intraarterial infusion of adenosine given under fasting conditions (n = 6) or superimposed on a euglycemic insulin clamp (n = 8). In the fasting state, adenosine-induced vasodilation (forearm blood flow from 2.6 +/- 0.6 to 6.0 +/- 1.2 ml min-1dl-1, P < 0.001) was associated with a 45% rise in muscle oxygen consumption (5.9 +/- 1.0 vs 8.6 +/- 1.7 mumol min-1dl-1, P < 0.05), and a doubling of forearm glucose uptake (0.47 +/- 0.15 to 1.01 +/- 0.28 mumol min-1dl-1, P < 0.05). The latter effect remained significant also when expressed as a ratio to concomitant oxygen balance (0.08 +/- 0.03 vs 0.13 +/- 0.04 mumol mumol-1, P < 0.05), whereas for all other metabolites (lactate, pyruvate, FFA, glycerol, citrate, and beta-hydroxybutyrate) this ratio remained unchanged. During euglycemic hyperinsulinemia, whole-body glucose disposal was stimulated (to 19 +/- 3 mumol min-1kg-1), but forearm blood flow did not increase significantly above baseline (2.9 +/- 0.2 vs 3.1 +/- 0.2 ml min-1dl-1, P = NS). Forearm oxygen balance increased (by 30%, P < 0.05) and forearm glucose uptake rose fourfold (from 0.5 to 2.3 mumol min-1dl-1, P < 0.05). Superimposing an adenosine infusion into one forearm resulted in a 100% increase in blood flow (from 2.9 +/- 0.2 to 6.1 +/- 0.9 ml min-1dl-1, P < 0.001); there was, however, no further stimulation of oxygen or glucose uptake compared with the control forearm. During the clamp, the ratio of glucose to oxygen uptake was similar in the control and in the infused forearms (0.27 +/- 0.11 and 0.23 +/- 0.09, respectively), and was not altered by adenosine (0.31 +/- 0.9 and 0.29 +/- 0.10). We conclude that in insulin-re15-76sistant patients with hypertension, adenosine-induced vasodilation recruits oxidative muscle tissues and exerts a modest, direct metabolic effect to promote muscle glucose uptake in the fasting state. Despite these effects, however, adenosine does not overcome muscle insulin resistance.

Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents.

OBJECTIVES: We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans. BACKGROUND: The mechanisms underlying postischemic LV dysfunction are largely unknown. METHODS: Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77+/-5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline. RESULTS: Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8% and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in control subjects. CONCLUSIONS: LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.

Obesity and carotid artery remodeling.

BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP). SUBJECTS/METHODS: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 µm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 µm, P=0.001, P<0.05 and P=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, P<0.0001). As compared with gender- and age-matched lean individuals, obese subjects had highly increased CCA LD and BP (P<0.0001 for both), but only slightly higher CWS (P=0.05) due to a significant increase in IMT (P=0.005 after adjustment for confounders). CONCLUSIONS: Our findings suggest that in obese subjects, the CCA wall thickens to compensate the luminal enlargement caused by body size-induced increase in SV, and therefore, to normalize the wall stress. CCA diameter in obesity could represent an additional biomarker, depicting the impact of altered hemodynamics on arterial wall.

111In platelet scintigraphy for the noninvasive detection of carotid plaque thrombosis.

BACKGROUND AND PURPOSE: Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect. METHODS: We compared the performance of (111)In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%. RESULTS: Positivity at (111)In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque. CONCLUSIONS: Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.

Impaired insulin action on skeletal muscle metabolism in essential hypertension.

Previous studies have shown that essential hypertension is frequently associated with insulin resistance. The tissues responsible for this metabolic alteration have not been defined. We tested the hypothesis that skeletal muscle is the site of insulin resistance of essential hypertension with the use of the perfused forearm technique. Eight hypertensive (age 42 +/- 3 years, body mass index 27 +/- 1 kg/m2, intra-arterial mean blood pressure 126 +/- 4 mm Hg) and seven normotensive (age 48 +/- 3 years, body mass index 26 +/- 1 kg/m2, mean blood pressure 95 +/- 4 mm Hg) male volunteers were studied. After glucose ingestion (40 g/m2), normal glucose tolerance in the patients was maintained at the expense of a heightened plasma insulin response, suggesting the presence of insulin resistance. During graded, local (intra-arterial) hyperinsulinemia encompassing the physiological range (12-120 milliunits/l), glucose uptake by forearm tissues was significantly (p less than 0.03) reduced in the hypertensive subjects as compared with the controls at each of five insulin steps, by 43% on the average. In addition, forearm lactate and pyruvate release were significantly less stimulated in the hypertensive than in the normotensive group (p less than 0.01 for both), presumably as a consequence of the decreased glucose influx. Forearm exchange of oxygen, carbon dioxide, lipid substrates (free fatty acids, glycerol, and beta-hydroxybutyrate), and potassium were similar in the hypertensive and normotensive groups in the basal state. Insulin had no effect on oxygen consumption, carbon dioxide production, and respiratory quotient in either study group, whereas it stimulated free fatty acids, glycerol, and potassium uptake to the same extent in the hypertensive and normotensive groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic angiotensin converting enzyme inhibition on glucose tolerance and insulin sensitivity in essential hypertension.

The relation between the renin-angiotensin-aldosterone (RAA) system and carbohydrate metabolism and insulin sensitivity in essential hypertension has not been investigated systematically. Twenty nondiabetic patients (age, 49 +/- 1 years; body mass index (BMI), 26.1 +/- 0.4 kg/m2) with essential hypertension (blood pressure, 155 +/- 3/105 +/- 1 mm Hg) received an oral glucose tolerance test (OGTT) at the end of a 1-month placebo period and again monthly during 3 months of angiotensin converting enzyme (ACE) inhibition (cilazapril, 5 mg/day). Furthermore, a two-step euglycemic insulin clamp was performed after placebo and again at the end of treatment. Blood pressure fell by 7 +/- 4/10 +/- 3 mm Hg (p less than 0.001), while BMI remained stable. On the euglycemic clamp, insulin-mediated (plasma insulin, 470 pM) whole body glucose use averaged 42.5 +/- 1.6 mumol.min-1.kg-1 before and 43.6 +/- 1.9 after ACE inhibition (p = NS). Substrate concentrations and oxidative rates and energy expenditure (as estimated by indirect calorimetry) were not altered by ACE inhibition, either in the fasting state or in response to insulin. In contrast, oral glucose tolerance was significantly (p less than 0.05) improved after treatment (area under OGTT curve (AUC), 240 +/- 24 versus 282 +/- 23 mmol 2 hr.l-1). The latter change was associated with enhanced (+16%, p less than 0.05) insulin responsiveness to glucose (estimated as the insulin AUC divided by the glucose AUC) throughout the 3 months of ACE inhibition. At baseline, both the OGTT and the clamp had a marked hypokalemic effect (mean decrements in plasma potassium of 0.75 +/- 0.05 and 0.92 +/- 0.05 mmol/l, respectively) in association with plasma aldosterone reductions of 30% and 50%. Chronic ACE inhibition caused a further 20% (p less than 0.03) lowering of plasma aldosterone concentrations but attenuated insulin-induced hypokalemia. Plasma sodium, which was unaltered by the pretreatment tests, fell during the posttreatment tests (by 3 mmol/l, p less than 0.001). In the urine, the ratio of the fractional excretion of potassium to that of sodium was decreased by both oral glucose (-22%, p less than 0.01) and ACE inhibition (-21%, p less than 0.001). Higher plasma potassium levels before treatment predicted a better blood pressure response to ACE inhibition (r = 0.60, p less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Seasonal influences on blood pressure in high normal to mild hypertensive range.

To investigate the seasonal influences on various arterial blood pressure measurements, 22 subjects in the high normal to mild hypertensive range were examined twice following the same protocol. In one group (13 subjects), measurements were first done in warm conditions and repeated 5-7 months later in cold conditions; in the second group (nine subjects) a reverse sequence was followed. Blood pressure was measured under casual conditions during a hand grip exercise test, mental arithmetic test, and submaximal multistage bicycle exercise test; during the following 24 hours, blood pressure was measured serially with a noninvasive ambulatory blood pressure recorder. Daily outdoor maximum and indoor laboratory temperatures were also obtained. In the cold season, significantly higher values (on the average by 5-10 mm Hg, p less than 0.01) were obtained in both groups for mean diastolic daytime blood pressure. For other measurements, a trend toward higher values in the cold season was observed in both groups, although statistical significance was not obtained in all instances. For nighttime measurements, irrespective of the seasonal sequence, lower values were observed in the second session. Significant correlations were found between the differences in the average daytime ambulatory blood pressures and the corresponding changes of daily maximum outdoor temperatures after 5-7 months. These observations indicate that arterial blood pressure may be strongly influenced by environmental temperature. This phenomenon should be taken into account both in the evaluation of the individual hypertensive patients and in the design and analysis of studies on arterial hypertension, especially when ambulatory blood pressure techniques are employed.

Mechanisms of coronary flow reserve impairment in human hypertension. An integrated approach by transthoracic and transesophageal echocardiography.

The purpose of this study was to investigate the different mechanisms responsible for an impairment of coronary vasodilator capacity in hypertensive subjects by an integrated echocardiographic approach, including transesophageal Doppler echocardiography, which allows noninvasive monitoring of coronary flow velocity in the left anterior descending artery during pharmacological vasodilation. The study population consisted of 17 healthy control subjects and 33 hypertensive subjects: 10 without hypertrophy, 16 with mild to moderate hypertrophy, and 7 with severe left ventricular hypertrophy. Mean systolic and diastolic flow velocities were monitored basally (together with indexes of myocardial oxygen demand, such as heart rate, myocardial inotropism, and left ventricular wall stress) and during infusion of low-dose (0.56 mg/kg per 4 minutes) and high-dose (0.84 mg/kg per 9 minutes) dipyridamole. Coronary reserve was assessed as the ratio of mean diastolic velocity after high-dose dipyridamole and basal diastolic velocity, and minimum coronary resistance as the ratio of diastolic blood pressure and diastolic velocity after high-dose dipyridamole. Compared with the control group, in all hypertensive groups, coronary reserve was similarly decreased (3.54 +/- 0.84 versus 2.59 +/- 0.42, 2.29 +/- 0.46, and 2.43 +/- 0.71; P < .01) and minimum resistance increased (0.56 +/- 0.15 versus 0.75 +/- 0.31, 0.75 +/- 0.19, and 0.78 +/- 0.21 mm Hg.s-1.cm-1; P = NS). These results confirm that coronary reserve in hypertensive individuals is reduced even before the occurrence of left ventricular hypertrophy. The reduction in coronary reserve depends on both an increase in resting coronary flow and an impairment in maximal vasodilator capacity. An increase in resting flow is dependent on higher heart rate and wall stress in hypertensive subjects without ventricular hypertrophy and on increased myocardial mass in hypertensive subjects with hypertrophy. Hypertensive subjects with ventricular hypertrophy also demonstrated a significantly blunted response to low-dose dipyridamole.

Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study.

Subclinical hypothyroidism (sHT) is associated with dyslipidemia and enhanced cardiovascular risk. We assessed carotid artery intima-media thickness (IMT, high-resolution ultrasonography) and lipoprotein profile in 45 sHT patients (aged 37 +/- 11 yr) at baseline and after 6 months of randomized, placebo-controlled L-T(4) replacement. In comparison with 32 age- and sex-matched controls, sHT patients had elevated total and low-density lipoprotein (LDL) cholesterol and ApoB levels (P = 0.002, P = 0.0007, and P = 0.01, respectively) and higher mean-IMT values (P < 0.0001). In stepwise regression analysis, mean-IMT was positively related (r(2) = 0.71, P < 0.0001) to age, TSH, and LDL cholesterol. L-T(4) replacement significantly reduced both total and LDL cholesterol (P < 0.0001 for both) and mean-IMT (by 11%, P < 0.0001). The decrement in IMT was directly related to the decrements of both total cholesterol and TSH (P = 0.02 and P = 0.0001, respectively). We conclude that early carotid artery wall alterations are present in sHT patients. Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall cannot be clearly decided on the basis of the present results. However, the fact that L-T(4) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in subclinical hypothyroidism.

Renal scintigraphic captopril test in the diagnosis of renovascular hypertension.

Angiotensin converting enzyme (ACE) inhibitor-induced renal failure has been reported in bilateral renal artery stenosis and in stenosis in solitary kidneys, but not in unilateral renal artery stenosis. In these patients, however, a functional impairment of the kidney ipsilateral to the stenosis can often be detected after ACE inhibition by scintigraphic techniques employing glomerular radionuclide tracers like 99mTc-diethylenetriamine pentaacetic acid (DTPA). Dynamic renal scintigraphy with 99mTc-DTPA before and 1 hour after administration of captopril, 25 mg (renal scintigraphic captopril test; RSCT), was performed in a selected series of 39 hypertensive subjects with suspected renovascular hypertension. Changes in glomerular filtration rate induced by captopril on the individual kidney were estimated by assessing the early (120-180 seconds) DTPA uptake by the kidney. Values were expressed as the ratio between the kidney with the lower uptake and the contralateral one in 34 patients and as the ratio of the kidney counts to the injected dose in five patients with solitary kidneys, aortic coarctation, or both. Compared with precaptopril values, postcaptopril uptake decreased markedly in 14 subjects (-62.42 +/- 30.94 [SD]%; range, -25 to -100%) and decreased modestly or even increased in the other 25 (+0.57 +/- 9.83%; range, +28 to -13%). Of the 14 subjects considered to be RSCT-positive diagnostic workup revealed either established (10) or strongly suspected (2) renal artery stenosis in 12 and aortic coarctation in 2 subjects. In another patient with established renovascular hypertension, results of the RSCT were negative when performed in the supine position but became positive when repeated in the sitting position.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular filling: relationship with arterial blood pressure, left ventricular mass, age, heart rate and body build.

The relationships of age, heart rate, body build and, in particular, of arterial blood pressure and left ventricular mass to several Doppler indexes of diastolic function were evaluated in a series of 80 subjects with a wide range of blood pressure levels (106-217/68-144 mmHg). Body build and age results were inversely correlated to the indexes, reflecting the early contribution to left ventricular filling, whereas the increase in heart rate was associated with an increase in late diastolic contribution. Strong correlations (in most instances, P less than 0.0001) were observed with arterial blood pressure and left ventricular mass: the increase of these parameters was associated with a decrease of early transmitral peak velocity (E peak) and of early filling fraction, with an increase of late diastolic transmitral peak velocity (A peak) and of A:E ratio and, finally, with an increase of both deceleration time of E peak and acceleration time to A peak. Blood pressure or left ventricular mass were also confirmed as strong predictors of nearly all the Doppler-derived diastolic indexes by stepwise multiple regression analysis. When the subjects were subdivided into quintiles according to diastolic blood pressure and the average values of the five subgroups were compared, age, heart rate and body build results were similar in the quintiles while diastolic blood pressure increased stepwise by 10 mmHg. Analysis of variance showed significant differences for all the indexes of left ventricular filling except deceleration time of and acceleration time to E peak (P less than 0.05 to P less than 0.0001) and almost all the echo-Doppler indexes showed a linear trend with diastolic blood pressure and left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Early impairment of coronary flow reserve and increase in minimum coronary resistance in borderline hypertensive patients.

OBJECTIVE: To evaluate relations between coronary flow velocity and myocardial oxygen demand at rest, as well as coronary vasodilator capacity and flow reserve, in asymptomatic subjects with borderline hypertension as compared to normotensive controls and patients with sustained high blood pressure (HBP) and without left ventricular hypertrophy (LVH). SUBJECTS AND METHODS: Forty-two asymptomatic males were studied: 13 healthy normotensive volunteers; 12 subjects with borderline HBP and 17 asymptomatic subjects with sustained systemic hypertension. Coronary flow velocity in left anterior descending artery and coronary flow reserve were assessed by transesophageal echo-doppler at baseline and during intravenous adenosine infusion. Left ventricular mass, peak systolic wall stress (PSWS; Pa), and midwall fractional shortening (MFS; %) were obtained from M-mode images of the left ventricle in transthoracic long-axis view and in transesophageal transgastric view. RESULTS: Coronary flow velocity at baseline was not significantly different in the three groups, despite significantly higher rate-pressure product (RPP) in the hypertensive groups as compared with controls. Only in control subjects, was resting coronary flow velocity significantly correlated with RPP (y = 4279 + 200x, r = + 0.58, P < 0.05) and PSWS (y = 17.2 + 5.1 x, r = + 0.62, P < 0.05). Coronary reserve was 3.5 +/- 0.65 in controls and significantly lower (P < 0.05) in borderline hypertensive (2.87 +/- 0.46) and in sustained hypertensive subjects (2.66 +/- 0.56). Minimum coronary resistance was significantly increased in both hypertensive groups (1.30 +/- 0.29 and 1.39 +/- 0.48 mmHg/s per cm) as compared to normotensive controls (0.93 +/- 0.20 mmHg/s per cm, P < 0.01). CONCLUSIONS: In asymptomatic subjects with borderline hypertension and without LVH, a significant reduction in coronary flow reserve is already detectable and appears almost entirely related to an impaired coronary vasodilator capacity rather than to an increased myocardial oxygen demand.

Echocardiographic versus hemodynamic monitoring during attacks of variant angina pectoris.

Six attacks of variant angina (2 spontaneous, 4 induced by ergonovine) were studied in 6 patients by combined echocardiographic and hemodynamic monitoring. A decrease of percent systolic thickening of the ischemic wall, which occurred as early as the decrease in peak dP/dt of contraction, was detected before the onset of ST-segment elevation ("pre-electrocardiographic phase"). At this stage, no significant change in left ventricular (LV) end-diastolic pressure or end-diastolic diameter was observed. Subsequently, in the presence of clear-cut ST-segment elevation ("electrocardiographic phase"), percent systolic thickening (an index of regional function) reached its nadir, while dP/dt of contraction (an index of global function) was almost back to preischemic values. In this phase, a significant increase in LV end-diastolic diameter and end-diastolic pressure could be also detected. In the recovery phase, when the ST segment had returned to the isoelectric line ("post-electrocardiographic phase"), percent systolic thickening and dP/dt of contraction showed supernormal values, while LV end-diastolic pressure and end-diastolic diameter decreased below basal values. Thus, echocardiographic signs of impairment in LV mechanics are as early and sensitive as hemodynamic indexes during attacks of variant angina. Furthermore, information on morphologic characteristics and regional LV function, not available with hemodynamic monitoring, can be obtained by echocardiography.

Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group.

The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional myocardial blood flow and coronary reserve in hypertensive patients. The effect of therapy.

Patients with essential arterial hypertension demonstrate abnormal vasodilator capacity either during increased cardiac metabolic demand or during pharmacological vasodilation. Structural and functional damage to the coronary microcirculation has been proposed as one of the major causes of impaired coronary reserve in this disease. To assess the role of microvascular impairment in regional myocardial blood flow (MBF), 27 patients with essential hypertension were evaluated by dynamic positron emission tomography (PET) at rest, during atrial pacing and after dipyridamole infusion and compared with 13 healthy subjects. All patients had normal coronary arteries, 17 had moderate to severe hypertension and 10 had mild hypertension. Baseline mean MBF of 0.97 +/- 0.25 ml/min/g was significantly increased to 1.60 +/- 0.38 during atrial pacing and 2.35 +/- 0.95 after dipyridamole infusion (p < 0.01); however, mean flow during atrial pacing and after dipyridamole infusion was significantly lower than in healthy subjects (2.15 +/- 0.73 and 3.71 +/- 0.86 ml/min/g, p < 0.05 and p < 0.01, respectively). The MBF response to atrial pacing and dipyridamole infusion was similarly depressed in patients with mild and severe hypertension. The study was repeated after 6 months of antihypertensive treatment with the calcium antagonist verapamil or the angiotensin converting enzyme (ACE) inhibitor enalapril in a subgroup of 20 patients as part of a randomised, single-blind clinical trial. This study is still in progress; the initial 16 patients treated with verapamil or enalapril showed an obvious improvement in MBF values during atrial pacing and after dipyridamole infusion after 6 months of therapy (mean MBF: 2.10 +/- 0.64 and 2.99 +/- 1.63 ml/min/g, respectively, p < 0.05 vs pretreatment values). In conclusion, obvious impairment of MBF during atrial pacing and after dipyridamole infusion was observed in hypertensive patients with normal coronary arteries and this appeared unrelated to the severity of hypertension. Therapy with verapamil or enalapril improved coronary reserve and MBF response to an increase in myocardial oxygen demand.