Secondary prevention of coronary heart disease. A survey in an Italian primary care practice.

AIM: Management of patients with pre-existing coronary heart disease (CHD) relies for the most part on primary care physicians, an endeavour whose success is dependent upon acceptance and day-to-day application of guideline recommendations for secondary CHD prevention. The aim of this study is to analyze the status of secondary CHD prevention in an Italian primary care practice consisting of five partnered general practitioners attending 7006 subjects aged 15 years or more (3137 males, 3869 females) in Pontedera, Tuscany. METHODS: Retrieval of patients with history of CHD (previous myocardial infarction, [MI], and stable angina) from computerized records of the 5987 (2735 men, 3252 women) subjects aged 35-85 years enlisted in the practice. Patients with myocardial infarction <3 months at the time of the query were excluded. RESULTS: Search retrieved 153 (2.6%) subjects with history of CHD, 93 (3.4%) males and 60 (1.8%) females. Females were older and smoked more frequently than men. Antiplatelet drugs, beta-blockers, renin-angiotensin system blockers and statins were prescribed in 84%, 56%, 66% and 68% of the ischemic patients. LDL cholesterol targets of 100 and 70 mg/dL were achieved in only 60 (45%) and 11 (9%) respectively. Systolic blood pressure was above 140 mmHg in 25 out of 146 patients with available data. CONCLUSION: The surveys shows satisfactory uptake of guideline recommendations but also pitfalls in the implementation of secondary CHD prevention requirements. Targeted interventions on primary care physicians are critically needed to enhance further provider adherence to consensus guidelines for CHD risk reduction.

Dysglycaemia in non-diabetic hypertensive patients: comparison of the impact of two different classifications of impaired fasting glucose on the cardiovascular risk profile.

The clinical correlates and risk profile of prediabetes (fasting plasma glucose (FPG) values in the upper normal limits but below the diabetic threshold) in hypertension, an insulin-resistant, prodiabetogenic condition, are scarcely known. For this reason, we evaluated 982 non-diabetic (FPG,<126 mg 100 ml(-1) and no antidiabetic treatment) referred hypertensive patients without a history of cardiovascular disease grouped by mild (100-109 mg 100 ml(-1)) and advanced (110-125 mg 100 ml(-1)) dysglycaemia compared with normal FPG (<100 mg 100 ml(-1)). FPG, total and high density lipoprotein (HDL) cholesterol, triglycerides and total white blood cell count were assessed by standard methodologies; 10-year predicted coronary heart disease (CHD) risk was approximated by the Framingham risk score (FRS). Metabolic syndrome (MetS) was diagnosed by standard categorical criteria using either 110 or 100 mg 100 ml(-1) as a threshold for impaired fasting glucose (IFG). FPG was above 110 in 13% and between 100 and 109 in 20% of patients. In both dysglycaemic groups, perturbed glucose homeostasis was associated with abnormally high fasting triglycerides, low HDL cholesterol, obesity, worse CHD risk profile and higher white blood cell count. MetS was highly prevalent and its distribution pattern was markedly influenced by the definitions of IFG based on different FPG cutoffs. Thus, even mildly perturbed glucose homeostasis associates with atherogenic dyslipidaemia, obesity and adverse risk profile in non-diabetic hypertensive patients. Because of its prediabetic nature, dysglycaemia should prompt measures to prevent new-onset diabetes, although the role of IFG as an independent risk factor awaits specifically designed intervention trials.

Is transcutaneous oxygen and carbon dioxide monitoring indispensable in short- and long-term therapeutic management of non-reconstructable lower critical limb ischemia?

AIM: The aim of this study was to evaluate the capacity of transcutaneous partial pressure of O(2) (TCpO(2)) and CO(2) (TCpCO(2)) to predict clinical response to pharmacological treatment in short- and long-term follow-up of unreconstructable critical limb ischemia (CLI) treated with prostanoids; to suggest a diagnostic and therapeutic algorithm able to define the possibility of prostanoid therapy in unreconstructable CLI at high risk of limb loss. METHODS: Twenty-six consecutive patients with CLI (21 with distal trophic lesions, 31 symptomatic limbs) considered unreconstructable after peripheral angiography and with a history of type 2 diabetes mellitus underwent daily parenteral Iloprost treatment for 2-3 weeks. RESULTS: Transcutaneous gas-analytic monitoring (TGM) in non-reconstructable CLI treated with Iloprost divided patients into 2 groups: early responders (ER) with increased TcpO(2) and normalization of TcpCO2, and non responders (NR) with unchanged TcpO(2) and TcpCO(2) parameters. In the NR who underwent a second cycle of Iloprost within a few months of the first, TGM further divided the patients into another subgroup of late responders (LR) with TcpO(2) and TcpCO(2) similar to the ER group and a subgroup of NR, who, after pharmacological treatment failure, should undergo eventual surgical re-timing and/or spinal cord stimulation in a final attempt to save the limb. CONCLUSIONS: In the short-term follow-up of CLI, a marked reduction in supine/dependent TcpO(2) and a marked increase in supine TcpCO(2) at the symptomatic forefoot proved to be significant predictors of major amputation risk. In the long-term follow-up period, TGM showed that, in ER and in LR, the favourable effect of pharmacological therapy observed in the first 6 months will disappear over the next 6 months, suggesting an algorithm of 2- to 3-week cycles of prostanoid therapy repeated every year. In NR treated with surgical and/or alternative therapies who did not undergo major amputations, prolonged instrumental TGM will provide a constant evaluation of metabolic parameters, thus providing the possibility to save the limb with additional pharmacological therapy.

Blood pressure independent association of microalbuminuria and left ventricular hypertrophy in hypertensive men.

BACKGROUND: Rather unique amongst the prognostic predictors, microalbuminuria (MA, albuminuria: 15-200 microg min-1) is associated with several cardiovascular risk factors including left ventricular hypertrophy (LVH). The relationship, usually assumed to reflect an increased blood pressure (BP) load on the heart and the kidney, may, however, represent more than a haemodynamic correlate. METHODS: To evaluate this possibility, we related MA to left ventricular mass index (LVMI) and other functional and structural echocardiographic parameters, office and 24-h BP, weight, lipids and smoking status in 330 never treated nondiabetic hypertensive men. RESULTS: The risk of MA increased linearly by ascending quartiles of LVMI and was 2.3-fold higher in the presence of LVH after adjustment for age, left atrial size, mean fractional shortening. Systolic BP, either office or 24 h, and smoking status were the only additional independent predictors in multivariate logistic regression models. The BP-adjusted risk of MA was about twofold higher in patients with LVH, either concentric or eccentric, and neutral in those with concentric remodelling compared with normal geometry. CONCLUSIONS: The association between elevated LVMI and MA independent of several other potential confounders, systolic BP in particular, is consistent with the existence of cardiac albuminuric factors, possibly of hormonal nature, which are to be identified more precisely. The extent to which LVH explains the predictive power of MA for morbid events independent of the BP load remains unknown.

Coronary microcirculation into different models of left ventricular hypertrophy-hypertensive and athlete's heart: a contrast echocardiographic study.

The study was carried out in two different models of left ventricular hypertrophy: athlete's heart and essential arterial hypertension. Three groups of strictly age-matched males were studied: one group of 10 young adult untreated essential hypertensive patients (H), a second group of 10 athletes (A), and a group of 10 healthy individuals as controls (C). A Sonos 5500 echograph with S4 harmonic transducer was used with Levovist (ultrasonic tracer) before and after dipyridamole injection; digitised images of quantitative myocardial contrast echocardiography were collected with Power Harmonic Doppler. Angio images were analysed using dedicated PC software by placing a region-of-interest on the septum. Peak intensity, half-time (HT), the area under the curve of appearance and disappearance of microbubbles at 2/3 of PI, both in absolute and indexed values (/LVMi), were sampled. The per cent increase of PI after dipyridamole was significantly higher in C (+73%, P < 0.01) than in H (+31%) and in A (+33%) (P < 0.05). The area of appearance was significantly lower in H in comparison with C and A, both at rest and after vasodilatation. The disappearance area after dipyridamole was significantly higher in C and in A (+124%) than in H (+104%) (P < 0.05). Some hypothesis could be made: an impairment in the coronary microcirculatory function in hypertensive patients could be because of an in-crease in the arteriolar resistance. Angiogenesis and several different functional adaptations are the mechanisms that allow an optimal distribution of oxygen and of substrates to the hypertrophied myocardium of the athletes.

Peripheral vascular disease is associated with abnormal arteriolar diameter relationships at bifurcations in the human retina.

Arterial diameters at branch points are believed to conform to design principles that optimize circulatory efficiency and maintain constant shear stress across arterial networks. The objective of this study was to examine whether optimality at bifurcations is affected in individuals with atherosclerosis. Retinal images were analysed in normotensive men with abnormal ankle brachial index (n=13) and healthy controls (n=8), matched for age and clinic blood pressure. Compared with controls, men with peripheral vascular disease had adverse metabolic profiles (relative insulin resistance and greater total cholesterol levels). In healthy men, retinal arterial diameters at bifurcations conformed to predicted optimal values but in men with peripheral vascular disease, junction exponents deviated significantly from the optimum. Retinal arteriolar bifurcation angles did not differ significantly between the groups. Atherosclerosis is associated with abnormalities in the arteriolar network of the retina. In view of the importance of the endothelium in maintaining network co-ordination of branch diameters this is suggestive of a generalized abnormality of endothelial function in atherosclerosis.

Coronary microcirculation in essential hypertension: a quantitative myocardial contrast echocardiographic approach.

AIMS: The aims of the present study were: (a) to demonstrate whether quantitative myocardial contrast echocardiography can detect the increase in coronary flow induced by dipyridamole infusion vasodilation through the myocardial opacification due to the transit of microbubbles, both at rest and after dipyridamole induced vasodilation; (b) to explore the coronary microcirculatory function before and after dipyridamole in two different models: asymptomatic and relatively young hypertensive patients with a mild degree of left ventricular hypertrophy, and healthy controls. METHODS AND RESULTS: Two groups of strictly age-matched males were studied (case-control study): 10, relatively young and asymptomatic essential hypertensive patients with a mild degree of left ventricular hypertrophy with a normal left ventricular function, and 10 healthy controls. The main findings were: the microbubbles' appearance area was significantly lower in hypertensive patients than in controls (P<0.05) because of a significantly lower time to peak. The peak intensity at rest was higher in hypertensives than in controls (P<0.05); but the per cent increase after vasodilatory stimulus was significantly higher in controls (+71% in controls vs +31% in hypertensives; P<0.05). The microbubbles' disappearance area was comparable in both groups at rest; the per cent increase of this parameter after dipyridamole was significantly higher in controls (+124%) than in hypertensives (+90%) (P<0.05). The results achieved in this study documented that the coronary microcirculation in hypertensive patients presenting a mild degree of left ventricular hypertrophy, explored with quantitative myocardial contrast echocardiography, showed a different behaviour in comparison with controls, in the vasodilatory response to dipyridamole. CONCLUSION: The coronary microcirculation in hypertensives showed a reduced vasodilation capacity of the resistance arterioles under dipyridamole induced vasodilatation, and a possible impairment of the endothelium dependent vasodilation. This happened despite an increase in the left ventricular mass, where the relation between capillary bed distribution and hypertrophied myocardium (rarefaction phenomenon) is not completely respected.

Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension.

This paper reviews the existing epidemiological and clinical evidence about the relationships of non-diabetic microalbuminuria with cardiovascular risk factors such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy, adverse metabolic status, smoking habits, elevated angiotensin II levels, endothelial dysfunction, acute and perhaps subclinical inflammation. Because of that unique property of reflecting the influence of so many clinically relevant parameters, microalbuminuria may legitimately be defined as an integrated marker of cardiovascular risk, an unique profile among the several prognostic predictors available to stratify risk in hypertensive patients. Recent cohort studies also showed associations with cardiovascular morbidity and mortality independently from conventional atherogenic factors. This behaviour, whose understanding still needs further elucidation, suggests to measure albuminuria and to screen patients at a higher absolute risk in whom preventive treatment is expected to be more beneficial than in those with a lower absolute risk.

Calcium channel blockers, postural vasoconstriction and dependent oedema in essential hypertension.

Treatment with calcium channel blocker (CCB)s, dihydropyridines and others, is frequently complicated by dependent oedema in the absence of sodium retention or cardiac failure, a bothersome side effect of unclear aetiology. The present paper reviews our own and other work dealing with the antagonism exerted by such drugs on postural vasoconstriction, a mechanism triggered by limb venous congestion during orthostasis and controlled through a local sympathetic axo-axonic reflex and increased myogenic tone in response to changes in transmural pressure. By stabilising capillary pressure, postural vasoconstriction counteracts fluid hyperfiltration consequent to gravitational stimuli, and consistent evidence shows attenuation of this response by L-type calcium channel blockers. Interference with the postural reflex control of skin blood flow may therefore contribute to dependent oedema, although cannot entirely explain its development. Attenuation of postural vasoconstriction may amplify the fluid hyperfiltration induced by CCBs through other mechanisms, such as imbalanced intracapillary pressure or enhanced vascular permeability, which are the main factors determining net fluid filtration into the interstitial compartment.

Cyclic variation of the myocardial integrated backscatter signal in hypertensive cardiopathy: a preliminary study.

BACKGROUND: Ultrasound tissue characterization studies realized through integrated backscatter analysis with end-diastolic sampling in hypertensive cardiopathy have demonstrated that abnormalities in the left ventricular myocardial ultrasonic texture are present in extreme forms of left ventricular hypertrophy (LVH). Such abnormalities are not evident in the athlete's heart. The aim of the present study was to analyze the ultrasonic backscatter myocardial indexes both as peak end-diastolic signal intensity and as cardiac-cyclic variation in two models of LVH: hypertensive cardiopathy and athlete's heart. METHODS: Three groups of 10 subjects each, all men of mean age (31.6+/-3.5 years), and of comparable weight and height, were analyzed. Group A comprised 10 cyclists of good professional level, while hypertensive patients were grouped in Group H. Both groups presented a comparable left ventricular mass (LVM). Group C included 10 healthy subjects acting as controls. The men with hypertension were selected on the basis of the results of ambulatory monitoring of the blood pressure according to ISH-World Health Organization guidelines (International Society of Hypertension). A 2D-color Doppler echocardiography with a digital echograph Sonos 5500 (Agilent Technologies, Andover, Massachusetts, USA), was carried out on all the subjects in the study for conventional analysis of the LVM and function. The ultrasonic myocardial integrated backscatter signal (IBS) was analyzed with an 'acoustic densitometry' module implemented on a AT echograph. The signal was also sampled with a region of interest (ROI) placed at interventricular septum and at posterior left ventricular wall level. The systo-diastolic variation of the backscatter was also considered, as cyclic variation index (CVIibs). RESULTS: According to the inclusion criteria, the LVM was comparable in groups A and H, but it was significantly higher than group C (left ventricular mass (body surface) (LVMbs)=154.5+/-18.7 (A), 146.8+/-25.5 (H), 101.4+/-12.4 (C), p < 0.001). The end-diastolic IBS did not show significant statistical differences among the three groups. The CVI(IBS) both at septum (30.5+/-5.3 (A), 13.2+/-13.1 (H), 27.2+/-7.3(C), p < 0.002) and posterior wall level (43.7+/-9.1 (A), 16.5+/-12.1 (H), 40.7+/-9.1 (C), p < 0.001) though, was significantly lower in the hypertensive patients than in both the athletes and the control group, where the results were comparable. CONCLUSION: A significant alteration of the myocardial CVIibs (both for septum and posterior wall) was found in the hypertensive model. This was probably the expression of an alteration in the intramural myocardial function.

Ultrasonic myocardial tissue characterization: a methodological review.

Ultrasonic myocardial tissue characterization represents a relatively new diagnostic tool which allows integration of the conventional echocardiographic evaluation, in order to obtain specific textural parameters which reflect the myocardial ultrastructural texture. In particular, through this approach it is possible to obtain two different types of information: the first is static and consists of the absolute myocardial echo intensity that reflects the ultrastructural myocardial changes in different diseases; the second is dynamic and is related to the variations of echo intensity during the cardiac cycle which seem to be linked, even though not linearly, to the intrinsic myocardial contractility. Our research group has extensively applied this methodological approach to different pathophysiological models, in particular to essential hypertension. In the present review the technological evolution of the method and comparison with other research groups' experience with the specific pathophysiological models, are shown and discussed.

Microalbuminuria, pulse pressure, left ventricular hypertrophy, and myocardial ultrasonic tissue characterization in essential hypertension.

Microalbuminuria (UAE) may be considered a marker of systemic vascular dysfunction, while pulse pressure (PP) is an indicator of the stiffness of vascular conduits. Both these parameters, together with left ventricular hypertrophy (LVH), are linked to cardiovascular morbidity in hypertensive patients. The aim of this study was the analysis of the possible relationships among UAE, PP, and LVH with ultrasonic myocardial textural parameters, which are altered in hypertensives patients. A group of male (n = 70) essential hypertensive patients (mean age: 58 +/- 7 yr) was analyzed with a group of age-comparable normotensive healthy subjects as controls (n = 32). Ambulatory blood pressure monitoring (ABPM) was performed with an oscillometric monitor; UAE was measured by nephelometry. A conventional 2D-Doppler echocardiography (to analyze left ventricular mass: LVM) and a quantitative analysis of the echocardiographic digitized imaging with the use of a calibrated digitization system (to calculate the septum and the posterior wall textural parameters) were performed on all subjects. The myocardial mean gray level was calculated to derive the cyclic variation index (CVI). The CVI was significantly lower in hypertensives both for the septum (- 16.3 +/- 22.8 vs 34.7 +/- 15.3%; p < 0.001) and for the posterior wall (- 15.2 +/- 23.6 vs 38.2 +/- 15.4%; p < 0.001). A significant negative correlation was found between logUAE and the CVI of the septum (r = -0.42; p < 0.001), between the PP and the CVI of the septum (r = -0.40; p < 0.002) and between the CVI and the LVM (r = -0.38; p < 0.001). Multiple regression analysis having as dependent variable the CVI at septum level showed as significantly related independent variables: PP (p < 0.01), logUAE (p < 0.001), and LVM (p < 0.05) (multiple R: 0.76, squared multiple R: 0.57; p < 0.001). It was found that LVM, logUAE, and PP are all correlated with textural parameters, and the CVI can be considered a sensitive parameter in the identification of an abnormal myocardial texture in hypertension. A high level of arterial stiffness and the presence of vascular dysfunction in essential hypertension could participate in the determination of myocardial alterations and permit the identification of patients with the worst prognosis in terms of morbidity or mortality due to cardiovascular events.

Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular disease.

Subclinical increases in albuminuria (microalbuminuria) predict morbid events, but the reasons for that are still not understood in full. This paper reviews the existing evidence regarding the relationships of non-diabetic microalbuminuria and cardiovascular disease, the underlying assumption being that endothelial dysfunction contributes both to atherosclerotic macrovascular disease and renal microvascular disease of which albuminuria is a marker. Much data support that concept, and suggest a preferential link with endothelial activation in response to acute and subclinical inflammatory stimulation, although further studies are needed to establish the exact cause-effect mechanisms. Epidemiological studies also show associations with cardiovascular events, and some recent prospective results also indicate the power of microalbuminuria to predict risk independently from conventional atherogenic factors. Thus, microalbuminuria might be considered as an integrated marker of cardiovascular risk sensitive to systemic vascular status in addition to other parameters such as blood pressure levels, glucose metabolism, smoking habits, a profile rather unique among the prognostic predictors available to stratify risk in hypertensive patients.

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men.

BACKGROUND: The reasons why microalbuminuria (albuminuria > or = 15 microg/min), an expression of a renal microcirculatory abnormality, predicts cardiovascular disease in essential hypertension are unsettled. To test the hypothesis that microalbuminuria represents a marker of subclinical atherosclerosis, we evaluated its association with common carotid artery (CCA) intima media thickness (IMT), a measure of preclinical atherosclerosis and an independent predictor of cardiac and cerebrovascular events, in uncomplicated essential hypertensive individuals. MATERIALS AND METHODS: Albuminuria, ultrasonographic CCA IMT (the mean of six bilateral far wall measurements within 1.5 cm proximally to the flow divider), brachial blood pressure (BP), smoking habits and lipids were evaluated in 136 stage 1-3 untreated essential hypertensive men free of cardiovascular disease. RESULTS: CCA IMT did not differ between normo- (n = 99) and microalbuminuric (n = 37) patients. The correlation between CCA IMT and albuminuria was not significant, and the prevalence of microalbuminuria across IMT quartiles was not different. Microalbuminuric patients showed higher systolic BP and that parameter was the only independent correlate in a multivariate logistic regression model including also age, CCA IMT, diastolic BP, lipids and smoking habits as independent variables and microalbuminuria as the dependent one. CONCLUSION: This cross-sectional study in hypertensive subjects free of cardiovascular disease has shown a dissociation between microalbuminuria and CCA IMT, a surrogate measure of subclinical atherosclerosis, and a parameter linearly related to cardiovascular events. The data do not support the theory of microalbuminuria as a surrogate measure of subclinical atherosclerosis, while confirming the importance of systolic BP levels as an independent correlate of increased albuminuria in essential hypertension. Journal of Human Hypertension (2000) 14, 831-835

Simvastatin, capillary permeability, and acetylcholine-mediated vasomotion in atherosclerotic, hypercholesterolemic men.

OBJECTIVES: The aim of this study was to test the effect of high-dose simvastatin therapy on vascular permeability, a key variable in the atherogenic process, and endothelial-mediated vasodilator responses in patients with hypercholesterolemic atherosclerosis. METHODS: The transcapillary albumin escape rate (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of macromolecular permeability of capillary endothelium) and forearm vasodilatation (venous plethysmography) to intraarterial acetylcholine and sodium nitroprusside (7.5, 15, 30 microg/min and 0.8, 1.6, and 3.2 microg/min respectively, 5 minutes at each rate) to account for endothelium-dependent and independent mechanisms, were measured at baseline and after 1-month simvastatin (40 mg once daily) in 16 hypercholesterolemic (low-density lipoprotein cholesterol >130 mg/dL), atherosclerotic men. Thirteen healthy, untreated subjects were the controls. RESULTS: Baseline TERalb was higher and responsiveness to both acetylcholine and sodium nitroprusside was depressed in patients compared with controls. One-month high-dose simvastatin reduced low-density lipoprotein cholesterol by 39%, normalized TERalb, and improved local vasomotor responses to acetylcholine, without modifying those to sodium nitroprusside. Changes in TERalb and acetylcholine-mediated vasodilatation were dissociated and unrelated to lipid modifications. CONCLUSIONS: Low-density lipoprotein cholesterol reduction through 1 month of high-dose simvastatin normalized the exaggerated transvascular albumin leakage of patients with hypercholesterolemic atherosclerosis, perhaps by restoring an exaggerated endothelial permeability, apparently through mechanisms independent of circulating lipids. Improvements in acetylcholine-mediated vasomotion were also evident, but were dissociated from TERalb, demonstrating a heterogeneous behavior of the 2 indices of endothelial function in response to high-dose statin treatment.

The potential prognostic value of ultrasonic characterization (videodensitometry) of myocardial tissue in essential arterial hypertension.

BACKGROUND: Left ventricular hypertrophy (LVH) and the geometric shape of the left ventricle are well-established important risk factors for cardiovascular morbidity and mortality in the hypertensive population. Videodensitometry is an alternate echocardiographic approach to the study of myocardial structural and functional alterations in essential hypertension. OBJECTIVES: To analyze the behavior of the ultrasonic videodensitometric parameter for various subgroups of a hypertensive population; first according to the severity of LVH (group A, without LVH; group B, with mild-to-moderate LVH; and group C, with severe LVH) and second according to geometric adaptation of left ventricle to pressure-volume overload of essential hypertension (group NG, normal geometry; group CR, concentric remodeling; group CH, concentric hypertrophy; and group EH, eccentric hypertrophy). METHODS: For 70 male, essential hypertensive patients and 32 normotensive healthy subjects matched for age (58 +/- 7 years) and sex as controls (group N) we performed ambulatory blood pressure measurements for the evaluation of 24 h mean systolic and diastolic blood pressures, conventional two-dimensional Doppler echocardiography to evaluate left ventricular performance and left ventricular mass index, and digitization of left ventricular parasternal long-axis echocardiographic images. For regions of interest selected within the septum and the posterior wall, the mean gray levels were calculated at end-systole and end-diastole. The resulting values were used to estimate the percentage cyclic variation index (CVI). RESULTS: The results according to left ventricular mass index were CVI for septum group N 34.7 + 16.3%; group A - 0.18 +/- 16%, group B - 13 +/- 19%, and group C - 22 +/- 12% (P < 0.001); and CVI of posterior wall, group N 38.2 +/- 15.4%, group A -0.75 +/- 16%, group B -16 +/- 16% and group C -16 +/- 13% (P< 0.001). According to left ventricular geometry CVI for septum were group NG 0.6 +/- 24%, group CR 1.9 +/- 17%; group CH - 25.4 +/- 18%, and group EH -17.1 +/- 20% (P < 0.01). CVI of posterior wall were group NH -5.8 + 24%, group CR 6.4 +/- 23%, group CH -29 +/- 20%, group EH -20 +/- 21 (P < 0.01). CONCLUSIONS: Our results demonstrate that subjects with high left ventricular masses and those with concentric hypertrophy, which have the worst prognostic impacts, have the most significant changes in CVI. Furthermore, videodensitometric findings are quite different even among the subgroups with mild-to-moderate left ventricular hypertrophy and eccentric hypertrophy. Therefore this videodensitometric approach could provide some useful information for better definition of cardiovascular risk in hypertension.

Transvascular albumin leakage and forearm vasodilatation to acetylcholine in essential hypertension.

The impact of hypertension on microvascular permeability and nitric oxide-mediated endothelial vasomotion in humans has been studied by measuring either the transcapillary albumin escape rate (TERalb, a measure of permeability through systemic capillary endothelium where most of the albumin permeation takes place) and forearm vasodilatation to locally infused acetylcholine (used as a probe for the nitric oxide-releasing potential of arteriolar endothelial cells). It is unknown, however, how the two parameters relate to each other in the same hypertensive subject. This piece of evidence may enhance our understanding about the relative effect of hypertension on two biological functions (ie, permeability and nitric oxide-mediated vasomotion), both dependent on vascular endothelium, and also may allow to appreciate in greater detail the profile of parameters frequently used as markers of microvascular dysfunction in human hypertension. For these reasons, TERa1b (the 1-h decline rate of intravenous 125I-albumin) and forearm vasodilatation (strain gauge venous plethysmography) to graded intraarterial acetylcholine infusion were measured in 44 never-treated men with uncomplicated essential hypertension, and 15 male normotensive controls with comparable age, lipids, and proportion of current smokers. TERalb was increased in patients, whereas acetylcholine-mediated vasodilatation did not differ significantly between the two groups, indicating a heterogeneous impact of elevated blood pressure on capillary permeability and endothelial vasomotion in still uncomplicated mild to moderate essential hypertensive patients. The dissociation between TERalb and forearm responsiveness to acetylcholine also demonstrates that different endothelial-dependent biologic parameters do not behave uniformly in human hypertension.

Ultrasonic myocardial textural parameters and midwall left ventricular mechanics in essential arterial hypertension.

BACKGROUND: The evaluation of the systolic left ventricular performance in hypertensive patients presents some problems related to left ventricular hypertrophy (LVH) which alters the ventricular geometry. The videodensitometric textural ultrasonic analysis of hypertensive myocardium has provided evidence of impairment in the cyclic variation of the mean gray level. This might be considered as an index of intrinsic myocardial function. OBJECTIVES: The aim of the present study was to analyse the connection between the midwall fractional shortening and end-systolic stress. The ultrasonic textural parameters in hypertensive patients, arranged in different groups according to the level of LVH and relative wall thickness, were also evaluated. METHODS: A group of age-matched (58 +/- 7 years) male essential hypertensive patients (n = 70) were compared to a group of normotensive and healthy subjects used as controls (n = 32). All subjects performed a conventional 2D-Doppler echocardiography to analyse the left ventricular performance. A quantitative analysis of the echocardiographic digitised imaging was also carried out with the help of a calibrated digitization system in order to calculate the septum and the posterior wall textural parameters. The myocardial mean gray level was calculated to derive the cyclic variation index (CVI). RESULTS: When subjected to a higher meridional end-systolic stress, the hypertensive patients showed a significantly lower midwall fractional shortening than the control patients. The CVI was also significantly lower in the hypertensives group, both for the septum wall (-16.3 +/- 22.8 vs34.7 +/- 15.3%; P < 0.001) and the posterior wall (-5.2 +/- 23.6 vs 38.2 +/- 15.4%; P < 0.001). A significant correlation was found between the midwall fractional shortening (MFS) and the textural parameters, and between these two variables and the end-systolic stress. CONCLUSION: The CVI was found to be a highly sensitive parameter in the identification of abnormal echodensity in essential hypertension. The CVI was significantly lower in patients with concentric hypertrophy in comparison with other left ventricular geometric models. This parameter could be considered as an index of the intrinsic myocardial function, being related, in essential hypertension, to midwall fractional shortening and to end-systolic stress. Journal of Human Hypertension (2000) 14, 9-16.

Amlodipine, enalapril, and dependent leg edema in essential hypertension.

Calcium channel blockers (CCBs) blunt postural skin vasoconstriction, an autoregulatory mechanism that minimizes gravitational increases in capillary pressure and avoids fluid extravasation when standing. To evaluate the dose-response relation between this pharmacological interference and dependent edema, a frequent side effect of CCBs during antihypertensive treatment, skin blood flow (laser Doppler flowmetry) at the dorsum of the foot, both supine and with the limb passively placed 50 cm below the heart level, and leg weight (Archimedes principle) were measured at baseline, during increasing doses of the dihydropyridine amlodipine (5 and 10 mg UID each for 2 weeks), and after drug withdrawal in 10 hypertensive men. Because angiotensin-converting enzyme inhibitors may attenuate ankle swelling by CCBs, those parameters were evaluated according to a similar design during amlodipine (10 mg UID) and enalapril (20 mg UID) combined (n=10). As a control, the effect of enalapril monotherapy (10 and 20 mg UID for 2 weeks each) was evaluated in a third series of patients (n=8). Amlodipine (5 mg UID) increased leg weight without modifying postural vasoconstriction (the percent skin blood flow decrease from horizontal to dependent position), which indicates that extravascular fluid shift was independent of postural skin vasoconstriction. At 10 mg UID, however, amlodipine blunted postural vasoconstriction and increased leg weight further, which suggests that skin blood flow autoregulation limited additional fluid transfer. Both parameters normalized after drug withdrawal. Enalapril per se did not affect cutaneous vasomotion or leg weight but reduced the amount of dependent fluid extravasation by the CCB despite a persistent antagonism for postural vasoconstrictor responses.