Changes in rat ventricular isomyosins with regression of cardiac hypertrophy.

The changes in ventricular isomyosin composition and Ca2+-activated ATPase activity occurring with regression of both hypertension and cardiac hypertrophy were investigated by using polyacrylamide gel electrophoresis under nondenaturing conditions, heavy chain peptide mapping, and an enzymatic assay. Eight control male Wistar rats and 14 two-kidney, one clip (Goldblatt II) hypertensive rats were studied from the fifth week of age. At 10 weeks of age, five Goldblatt II rats and four normotensive controls were killed. Five other Goldblatt II rats underwent nephrectomy of the ischemic kidney, which resulted in subsequent normalization of blood pressure. The remaining four control, four Goldblatt II rats, and five nephrectomized rats were killed at 15 weeks of age. Both the 10- and 15-week-old hypertensive rats had a significantly higher (p less than 0.001) biventricular weight to body weight ratio than the age-matched controls (3.84 +/- 0.76 X 10(-2) vs 2.75 +/- 0.25 X 10(-2); 5.93 +/- 2.26 X 10(-2) vs 2.65 +/- 0.17 X 10(-2]. The 15-week-old nephrectomized rats had a biventricular weight to body weight ratio (2.90 +/- 0.25 X 10(-2] close to that of age-matched controls and significantly lower (p less than 0.05) than that of age-matched hypertensive rats. In both the 10- and 15-week-old hypertensive rats left ventricular myosin Ca2+-activated ATPase activity was significantly lower (p less than 0.001) than in the age-matched controls (0.44 +/- 0.03 vs 0.59 +/- 0.06; 0.24 +/- 0.05 vs 0.48 +/- 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular myosin and creatine-kinase isoenzymes in hypertensive rats treated with captopril.

In the myocardium, myosin and creatine kinase isoforms possess different capacities for using O2 and energy-rich phosphates. We studied electrophoretically the distribution of these isoforms in 19 hypertensive rats (two-kidney, one clip model of hypertension) and in age-matched controls. After 6 weeks of hypertension, seven rats were treated with captopril (2 mg/kg daily) for 4 weeks, six were left hypertensive for another 4 weeks, and the remaining rats were killed under ether anesthesia. In the latter, ventricular mass was significantly higher than in controls; V3 isomyosin was 32.3 +/- 6.8% versus 0%, and both creatine kinase-MB and -BB were increased at the expense of creatine kinase-MM (creatine kinase-MB = 29 +/- 2.8% vs. 14.7 +/- 1.8%, p less than 0.001; creatine kinase-BB = 3.1 +/- 0.6% vs. 1.7 +/- 0.8%, p less than 0.001). After 10 weeks of hypertension, ventricular mass, V3 isomyosin, and both creatine kinase-MB and -BB isoforms were found to be persistently higher than in controls. At the same time, captopril-treated rats showed reduced but not normalized blood pressure levels, normalized ventricular mass, and prevalence of the V1 isomyosin (56.9 +/- 22% vs. 47.9 +/- 23.8% in normotensive controls, p = NS). However, higher levels of creatine kinase-MB and -BB were still found in these rats in comparison with the normotensive controls (creatine kinase-MB = 22.4 +/- 5.4% vs. 15.8 +/- 2.8%, p less than 0.025; creatine kinase-BB = 2.3 +/- 0.1% vs. 1.8 +/- 0.3%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid--lipoprotein composition in hypercholesterolemic children and their parents.

In 13 hypercholesterolemic children, re-screened for serum cholesterol after a 1-year interval, hypercholesterolemia was confirmed in only 61.5% of the cases. A tentative explanation seems to be the statistical principle of regression towards the mean. The lipid--lipoprotein analysis showed that serum and LDL cholesterol concentrations in the 13 hypercholesterolemic children and their parents were significantly higher compared to controls (children and parents). At re-screening, hyper-LDL cholesterolemia was present in only 8 of the 13 children (61.5%); 4 cases exhibited hyper-HDL cholesterolemia (30.7%). The high prevalence of the parents repeating the lipoprotein abnormality and the electrophoretic pattern found in the propositi (children) confirms the familial aggregation of the hypercholesterolemic states (hyper-LDL and hyper-HDL cholesterolemia). In conclusion the results of our study stress the importance of determining the lipid--lipoprotein composition, rather then merely evaluating total serum cholesterol in order to make a correct diagnosis of the hypercholesterolemic state. It should also be emphasized that the lipoprotein disturbances and their familial aggregation may be detected early in childhood, suggesting that the familial screening for risk factors of atherosclerosis should be done at pediatric age.

Hematoporphyrin binding to cultured aortic smooth muscle cells from spontaneously atherosclerotic turkey.

Porphyrins are known to be accumulated in vivo by tumors and atherosclerotic plaques. We studied the interaction of cultured aortic smooth muscle cells (SMC) from spontaneously atherosclerotic Broad Breasted White Turkeys (BBWT) with free hematoporphyrin (Hp) and low density lipoprotein (LDL)-Hp complexes. A significantly higher binding of LDL-Hp to SMC as compared to free Hp was observed. These data indicate that porphyrin binding to vascular SMC represents a possible mechanism for porphyrin accumulation by atherosclerotic plaques. This process is mediated, at least in part, by LDL.

Left ventricular hypertrophy in hypertension. Changes in isomyosins and creatine-kinase isoenzymes.

In hypertension, the heart of small mammals can express different isoenzymic forms of proteins under the influence of overload and other modulating factors. The increase in ventricular mass is generally paralleled by progressive changes in the isoforms of at least two proteins that are involved in the contraction process, namely, myosin and creatine-kinase. This review summarizes the biochemical and molecular changes occurring during progression and with regression of cardiac hypertrophy in rats, humans, and other animals, and focuses on the role played by antihypertensive drugs in modulation of ventricular isomyosins. The implications of these observations for humans remain to be fully determined.

ACE inhibitor ramipril is more effective than the beta-blocker atenolol in reducing left ventricular mass in hypertension. Results of the RACE (ramipril cardioprotective evaluation) study on behalf of the RACE study group.

OBJECTIVES: To compare the effect of the angiotensin converting enzyme (ACE) inhibitor ramipril with that of the beta-blocker atenolol on reversal of left ventricular hypertrophy, on blood pressure and on other echocardiographic parameters. DESIGN: The study was conducted in accord with the PROBE (prospective randomized open blinded endpoint) design. Randomized treatment either with ramipril or with atenolol was continued for 6 months, and echocardiograms were recorded before and after 3 and 6 months of treatment. The echo tracings were blindly evaluated in a single reading centre. METHODS: M-mode, two-dimensional guided echocardiography was used to measure left ventricular wall thicknesses and dimensions, from which left ventricular mass was calculated, according to the Penn convention. RESULTS: Of 193 patients at 16 centres, 111 had echocardiograms that could be quantitatively evaluated. The primary analysis of the study was performed using data from those patients. In addition, echocardiograms of 88 patients were analysed on an 'according to protocol' basis (patients with preset values of left ventricular mass). Systolic and diastolic blood pressures were significantly reduced both by ramipril and by atenolol without any significant difference between the two drug treatments. The heart rate was significantly reduced by atenolol only. Both the 'primary' and the 'according to protocol' analyses showed that the left ventricular mass was significantly reduced by ramipril only. Comparison between treatments according to a multivariate analysis demonstrated a significantly greater reduction in left ventricular mass during ramipril than during atenolol treatment. CONCLUSIONS: The present study is the first of suitably large size in which a direct comparison of the effects of an ACE inhibitor and a beta-blocker on echocardiographic left ventricular mass has been performed. It has demonstrated that ramipril is more effective than atenolol in reversing left ventricular hypertrophy in essential hypertensive patients.

Clinical results of the Verapamil inHypertension and Atherosclerosis Study. VHAS Investigators.

OBJECTIVE: The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. DESIGN: After a 3-week placebo run-in period, 1414 hypertensive patients [692 men and 722 women, aged 53.2 +/- 7 years, blood pressure 168.9 +/- 10.5/ 102.2 +/- 5.0 mmHg (means +/- SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. RESULTS: After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P < 0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to < or = 90 mmHg or to < or = 95 mmHg with a > or = 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P < 0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P < 0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K < 3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P < 0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). CONCLUSION: Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.

Prevalence of episodes of ST-segment depression among mild-to-moderate hypertensive patients in northern Italy: the Cardioscreening Study.

OBJECTIVES: To assess the prevalence of episodes of ST-segment depression in a population of consecutive patients with mild-to-moderate essential hypertension who are free of clinical signs of coronary artery disease. METHODS: The study involved 28 Italian centers that enrolled 414 hypertensive patients (aged 50-70 years; diastolic blood pressure > or = 95-115 mmHg or systolic blood pressure > or = 150-220 mmHg, or both, 10 days after withdrawal of medications). Silent myocardial ischemia was assessed by means of exercise stress testing and 48 h Holter monitoring. An ischemic episode was defined as a horizontal or downward sloping ST-segment depression > or = 100 microV, occurring 80 ms after the J point, and lasting for at least 1 min. RESULTS: Of the 414 patients enrolled, 411 completed the exercise stress test. During the test significant ST-segment depression occurred for 25 patients (6.1%) and all episodes but one were asymptomatic and not associated with arrhythmias. Of the 396 patients for whom we analyzed a 48 h Holter recording, 43 (10.9%) had at least one episode of ST-segment depression and seven of these had also had one during the exercise stress test The median number of episodes per patient was five (range 1-19), median duration was 9 min (range 1-20 min), and the mean amplitude of the ST-segment depression was 190 +/- 180 microV. None of these episodes was associated with symptoms and all of them occurred under resting condition. Patients with (n = 61) and without (n = 335) ST-segment depression during Holter monitoring or exercise stress testing had similar ages (59 +/- 6 versus 58 +/- 6 years) and did not differ for tobacco smoking, plasma lipid levels, blood pressure values and prevalence of echocardiographic left ventricular hypertrophy (57% of patients had left ventricular mass indexes > or = 134 g/m2 for men and > or = 110 g/m2 for women in both groups). Women had a higher prevalence of ST-segment depression than did men during Holter monitoring [32 of 183 (17.5%) versus 11 of 213 (5.2%)], whereas the prevalences of ischemia during the exercise stress test were similar. Female sex was the only significant factor associated with the occurrence of silent myocardial ischemia [odds ratio 2.56 (95% confidence interval 1.40-4.71)]. CONCLUSIONS: Our results show that 15% of patients with mild-to-moderate hypertension, who are free of clinical signs of coronary artery disease, experience episodes of ST-segment depression during Holter monitoring or exercise stress testing. Most of these episodes are asymptomatic and are not associated with the severity of hypertension, the presence of left ventricular hypertrophy, and other risk factors for coronary artery disease. Episodes of ST-segment depression are more common for women than they are for men, particularly during Holter monitoring. The early detection of silent myocardial ischemia by Holter monitoring or by the exercise stress test might be useful for the identification of hypertensive patients who should be investigated further and administered a more specific treatment.

The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness.

BACKGROUND: It is unclear whether the carotid intima-media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principal results of the ultrasound substudy of the randomized, prospective, controlled, Verapamil in Hypertension and Atherosclerosis Study (VHAS). DESIGN AND METHODS: In 498 hypertensive patients in eight Italian centres, randomized to either verapamil (240 mg once a day) or chlorthalidone (25 mg once a day), a B-mode ultrasound scan was performed according to a standardized procedure at baseline and after 3, 12, 24, 36 and 48 months of treatment. The maximum intima-media thicknesses of the far walls of common, bifurcation and internal carotid arteries were measured bilaterally, and the following indices calculated: the mean thickness at the six measured sites, the mean thickness at the common and bifurcation sites and the single maximum thickness. The primary endpoint for treatment efficacy was the slope of the change over 4 years (rate of change, mm/year), corrected by using the initial mean over the six sites (baseline + 3 months) as a covariate (mm/year per mm). The patients were also classified into three strata according to their baseline single maximum thickness: those with normal carotid arteries (single maximum ( 1 mm), those with thickened carotid arteries (single maximum > 1 and < or = 1.5 mm and those with carotid plaques (single maximum > 1.5 mm). RESULTS: Among the 456 patients with satisfactory baseline ultrasound readings, 33% were classified with normal carotid arteries, 27% with thickened carotid arteries and 40% with plaques. In the intention-to-treat population (377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years), the rate of change in the mean thickness at the six sites measured was rather small (0.015 mm/year), but significantly (P < 0.05) smaller in patients with plaques (0.003 mm/year) than in patients with thickened or with normal carotids (0.023 and 0.025 mm/year, respectively). When related to initial values, the rate of change in the mean thickness at the six sites had a negative slope (-0.059 mm/year per mm, P < 0.01). Although rates of change in the carotid intima-media thickness in unstratified patients were not different in those treated with verapamil or with chlorthalidone, when changes in the mean thickness of six sites were related to the initial value, the slope of this relationship was significantly different in the two treatment groups (verapamil -0.082 versus chlorthalidone -0.037 mm/year per mm, P < 0.02). The blood pressure-lowering effect of the two randomized treatments was similar. Taking fatal and nonfatal, major and minor cardiovascular events together, there were 19 events in the verapamil group and 35 in the chlorthalidone group, with a significantly (P < 0.01) greater incidence in patients with plaques, and among patients with plaques in those who were randomized to chlorthalidone (P < 0.05). CONCLUSIONS: In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions. Changes in the carotid intima-media thickness were small in both groups, and the differences between the changes under the two treatments were consequently small, but the observation that these small differences in carotid wall changes were paralleled by differences in the incidence of cardiovascular events (better intima-media thickness regression with verapamil paralleled by a lower cardiovascular event rate) suggests that even small effects on carotid plaques may have clinical and prognostic relevance.

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis.

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universität München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.

Effects of captopril on renal function in hypertensive patients.

The effects of captopril (SQ 14225) on renal function were studied in 10 hypertensive patients. After 7 weeks of treatment (75 to 500 mg/day) renal plasma flow was practically unchanged and glomerular filtration rate was only slightly decreased despite a significant decrease in blood pressure. All indexes of glomerular capillary permeability and of tubular anatomic integrity remained normal during the treatment period.

Preliminary clinical experience with calcium antagonists in atherosclerosis. Verapamil in Hypertension Atherosclerosis Study Investigators.

Animal experiments have shown that the administration of calcium antagonists can prevent or slow the progression of atherosclerosis by inhibiting calcium overload and interfering with lipid metabolism and deposition. These encouraging results have prompted clinical trials to evaluate the effects of calcium antagonists (dihydropyridines and diphenylalkylamines) on atherosclerotic plaque formation. In patients with coronary heart disease, several studies have already shown that calcium antagonists can have a positive effect on plaque evolution, while in hypertensive patients no such study has been published to date. The Verapamil in Hypertension Atherosclerosis Study is an ongoing multicentre randomised double-blind parallel group trial comparing the antihypertensive efficacy of verapamil SR 240 mg/day with that of chlorthalidone 25 mg/day in 1464 patients with essential hypertension aged 40 to 65 years. In a randomised subgroup of patients (n = 550), who will be followed up for 3 years, B-mode ultrasonography is being employed to evaluate the effects of the 2 drugs on carotid wall thickness and carotid plaque development. Ultrasonographic evaluations are performed at baseline, after 3 months, and 1, 2 and 3 years after a standardised protocol to determine intimal-medial thickness in 4 segments of the extracranial carotid tree. The most interesting result to date is the high incidence of carotid alterations, with plaques present in 35% and arterial wall thickening in 31.8% of the 311 asymptomatic hypertensive patients processed so far. A preliminary evaluation of the antihypertensive efficacy of the trial medications after 6 months of double-blind treatment indicates a 63.5% response rate to monotherapy and a 7.8% drop-out rate because of drug inefficacy or intolerance.

Na/H and Li/Na exchange in red blood cells of normotensive and hypertensive patients with insulin dependent diabetes mellitus (IDDM).

It has been shown that red blood cell Li/Na exchange, also called countertransport (Li/Na CTT) is increased in patients with insulin dependent diabetes mellitus (IDDM) with clinical or subclinical nephropathy and elevated blood pressure. Because recent experimental evidence confirms that red cell Li/Na CTT is a mode of functioning of the Na/H exchange (Na/H CTT), we have measured both transport modes in 23 IDDM (16 hypertensive and seven normotensive) and in eight normotensive controls with normal glucose tolerance. Na/H and Li/Na CTT were significantly increased in hypertensive compared to normotensive diabetics and controls. Na/H CTT was 78 +/- 28 mmol/L cell/h in hypertensive IDDM, 50 +/- 21 in normotensive IDDM, and 55 +/- 24 in the controls. Li/Na CTT was 0.37 +/- 0.13 mmol/L cell/h, 0.27 +/- 0.10, and 0.25 +/- 0.11, respectively. Na/H and Li/Na CTT were significantly correlated (r = .38, P less than .05). The proximal tubule sodium reabsorption, measured as the fractional Li+ reabsorption, was significantly correlated to red cell Na/H CTT (r = .38, n = 29, P less than .05), but not to the Li/Na CTT (r = .21, n = 29). In conclusion this work confirms that Na/H and Li/Na CTT are function modes of the same transporter and that an increased activity of Na/H CTT might play a role in the blood pressure increase in IDDM.

Beats modulate blood pressure during running.

Blood pressure (BP) changes during running were studied in 25 subjects with intraarterial monitoring. Periodic pulse pressure variations ranging from 20 to 200 mm Hg were recorded throughout the exercise. To prove that these pressure oscillations were due to a "beat" phenomenon 10 athletes ran with a Teruflex container filled with saline: pressure changes up to +/- 62 mm Hg were recorded in the container. These pressure waves were added by computer to the sphygmic waves recorded intraarterially in the same subject during bicycle ergometry: the resultant tracing showed a beat-shaped pattern similar to that recorded during running.

Excess prevalence of extracranial carotid artery lesions in renovascular hypertension.

High renin hypertension has been associated with a higher risk of stroke than low-to-normal renin hypertension. Accordingly, we investigated prospectively the prevalence of the extracranial carotid artery lesions in a case-control study of 70 patients (38 women and 32 men, aged 16 to 77 years) without history or symptoms of cerebrovascular disease. Renovascular hypertension was diagnosed in 35 patients on the basis of the angiographic demonstration of renal artery stenosis and of the favorable outcome after revascularization. It was caused by atherosclerosis in 20 patients and by fibrodysplasia in 15. Each renovascular hypertensive patient was individually matched with a control with primary hypertension for sex, race, age, blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. Carotid arteries were evaluated by a High Resolution Duplex system (Biosound 2000, probe 4 cm, 8 mHz). Our results show that after the matching the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). In renovascular hypertensives the prevalence of carotid artery lesions (82.6%) was significantly (P less than .01) higher than in primary hypertensives (42.9%). The higher prevalence of lesions in renovascular hypertension was observed not only in patients with atherosclerosis (100% v 55%, P less than .001), but also in those with fibrodysplasia (57% v 27%, P less than .01). Thus, for the same demographic features and overall cardiovascular risk profile, renovascular hypertension carries a more detrimental effect on the carotid artery than primary hypertension.

Blood pressure changes during running in humans: the "beat" phenomenon.

In 20 runners the intra-arterial blood pressure changes determined by a long-distance run and by a maximal bicycle ergometric test were recorded by means of the portable Oxford system. A peculiar pattern of the phasic waves was observed throughout the run: continuous rhythmic pulse pressure oscillations ranging in frequency between 4 and 28/min and unrelated to respiration were detected. The shape of these oscillations prompted us to investigate whether they were due to a "beat" phenomenon, that is, to the combined effect of two waves with a nearly equal frequency. To test this hypothesis, during the run 10 athletes carried a fluid-filled container around the chest. The pressure waves recorded in the container were added by computer to those recorded intra-arterially during bicycle ergometry. The resultant harmonic showed a pattern similar to that recorded in the athlete's radial artery during running. Conversely, by subtracting the pressure waves recorded in the container from those simultaneously recorded at the radial artery during running, nearly flat tracings were obtained. The source of the beat phenomenon has therefore been identified in the wave, which generates inside the aorta and the great vessels at each foot-strike shock.

Hypertension and atherosclerosis.

A minimum level of blood pressure is necessary for atherosclerosis to develop, even in the presence of hypercholesterolemia. Experimentally and clinically we have both examples of atherosclerosis in which hypercholesterolemia is the dominant pathogenetic factor and others in which hypertension prevails (BBWT). The pathogenetic role of hypertension may be direct (wall stress) or mediated through humoral factors which characterize the different types of hypertension (renin, angiotensin, cathecholamines, endothelin, aldosterone). Probably, different forms of atherosclerosis will be identified in the future, with a different prognosis and therapeutical approach.

Atherosclerosis and calcium antagonists: the VHAS. The Verapamil-Hypertension Atherosclerosis Study (VHAS) Investigators.

Whether or not some classes of antihypertensive drugs have an anti-atherogenic action independent of the antihypertensive one has been investigated through a large series of experimental studies, primarily involving calcium antagonists. Most experimental investigations have shown a significant anti-atherogenic action of calcium antagonists, but only when the drug is administered simultaneously with the atherogenic stimulus (mainly cholesterol feeding). When the drug is administered weeks or months after the beginning of the atherosclerotic process (as in the Watanabe heritable hyperlipidemic rabbit), with a single exception, no antiatherogenic effect has been shown. The few clinical studies completed so far have been on symptomatic coronary patients. Little is known of the effects of calcium antagonists on asymptomatic lesions in the carotid arteries of hypertensive patients, in whom carotid plaques can be identified and followed-up by non-invasive ultrasound techniques. However, two such trials are underway. The Verapamil in Hypertension Atherosclerosis Study (VHAS) is an ongoing randomized trial, comparing the antihypertensive efficacy of verapamil 240 mg SR with chlorthalidone 25 mg in 1,464 essential hypertensives aged 40-65 years. In a random subgroup of patients (500), who will be followed for three years, B-mode ultrasonography is being carried out blindly to evaluate the effect of the two drugs on carotid wall thickness and on carotid plaques, when present. Preliminary baseline data are available in 440 of the hypertensive patients in whom ultrasound investigation was performed. The mean (+/- SD) age of these patients was 53.7 +/- 6.9 years; 32.5% had echocardiographically normal carotid walls; 30.9% showed intima-media thickening; and 36.6% had one or more plaques.(ABSTRACT TRUNCATED AT 250 WORDS)

INTERSALT in Italy: findings and community health implications.

In INTERSALT, an international cooperative study on electrolytes and blood pressure, significant associations were found, in the pooled data for 52 centres, between systolic BP and sodium (Na) excretion, body mass index (BMI), high alcohol intake and low potassium (K) excretion. We have assessed the status of the four Italian centres (Mirano, Gubbio, Bassiano, Naples) on these variables. The four centres examined a total of 794 men and women aged 20-59 years. Combined values were similar to overall INTERSALT levels for daily Na excretion (170 mmol) and BMI (25 kg/m2). The Italian centres had slightly higher potassium excretions (57 vs. 55 mmol/day), a higher prevalence of drinkers and a greater average alcohol consumption. Participants were divided into those below or above median levels of Na, K, BMI, and by alcohol intake (below or above 300 ml/week). Both systolic BP and diastolic BP were found to be lower in the more favourable stratum, for each variable. When all four factors were combined, those below median Na excretion and BMI, above median K, and with alcohol intake less than 300 ml/week had age-adjusted systolic BP 7.5 mmHg lower than those with less favourable levels of all four variables. The difference in adjusted diastolic BP was 4.3 mmHg. The data indicate the potential for lower population average BP with improved lifestyles.

Prevalence of atherosclerotic involvement of the internal carotid artery in hypertensive patients.

The prevalence of atherosclerotic involvement of the internal carotid arteries, as diagnosed through an echo-Doppler imaging system with pulsed Doppler spectral analysis was evaluated in 49 hypertensives who had a negative history for neurological symptoms and 49 matched controls. The prevalence was 24.5% in the hypertensive group and 10.2% in the controls with a statistically significant difference (chi-square = 6.07, P less than 0.01). Two hypertensives had severe stenosis (above 50% diameter reduction) and 7 had potentially embolic lesions (irregular surface, inhomogeneous appearance). No one of the matched controls was as severely involved. We conclude that arterial hypertension can account for enhanced prevalence of carotid artery disease in asymptomatic patients.