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Biomedical subjects

Damiano Rizzoni

Publications and source records attributed to Damiano Rizzoni.

At least 19 recordsLinked to original sources

A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients.

OBJECTIVES: We prospectively investigated the prevalence of curable forms of primary aldosteronism (PA) in newly diagnosed hypertensive patients. BACKGROUND: The prevalence of curable forms of PA is currently unknown, although retrospective data suggest that it is not as low as commonly perceived. METHODS: Consecutive hypertensive patients referred to 14 hypertension centers underwent a diagnostic protocol composed of measurement of Na+ and K+ in serum and 24-h urine, sitting plasma renin activity, and aldosterone at baseline and after 50 mg captopril. The patients with an aldosterone/renin ratio >40 at baseline, and/or >30 after captopril, and/or a probability of PA (by a logistic discriminant function) > or =50% underwent imaging tests and adrenal vein sampling (AVS) or adrenocortical scintigraphy to identify the underlying adrenal pathology. An aldosterone-producing adenoma (APA) was diagnosed in patients who in addition to excess autonomous aldosterone secretion showed: 1) lateralized aldosterone secretion at AVS or adrenocortical scintigraphy, 2) adenoma at surgery and pathology, and 3) a blood pressure decrease after adrenalectomy. Evidence of excess autonomous aldosterone secretion without such criteria led to a diagnosis of idiopathic hyperaldosteronism (IHA). RESULTS: A total of 1,180 patients (age 46 +/- 12 years) were enrolled; a conclusive diagnosis was attained in 1,125 (95.3%). Of these, 54 (4.8%) had an APA and 72 (6.4%) had an IHA. There were more APA (62.5%) and fewer IHA cases (37.5%) at centers where AVS was available (p = 0.002); the opposite occurred where AVS was unavailable. CONCLUSIONS: In newly diagnosed hypertensive patients referred to hypertension centers, the prevalence of APA is high (4.8%). The availability of AVS is essential for an accurate identification of the adrenocortical pathologies underlying PA.

Adrenal Cortex Neoplasms↗

Renal damage in primary aldosteronism: results of the PAPY Study.

Primary aldosteronism (PA) has been associated with cardiovascular hypertrophy and fibrosis, in part independent of the blood pressure level, but deleterious effects on the kidneys are less clear. Likewise, it remains unknown if the kidney can be diversely involved in PA caused by aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Hence, in the Primary Aldosteronism Prevalence in Italy (PAPY) Study, a prospective survey of newly diagnosed consecutive patients referred to hypertension centers nationwide, we sought signs of renal damage in patients with PA and in comparable patients with primary hypertension (PH). Patients (n = 1180) underwent a predefined screening protocol followed by tests for confirming PA and identifying the underlying adrenocortical pathology. Renal damage was assessed by 24-hour urine albumin excretion (UAE) rate and glomerular filtration rate (GFR). UAE rate was measured in 490 patients; all had a normal GFR. Of them, 31 (6.4%) had APA, 33 (6.7%) had IHA, and the rest (86.9%) had PH. UAE rate was predicted (P < 0.001) by body mass index, age, urinary Na+ excretion, serum K+, and mean blood pressure. Covariate-adjusted UAE rate was significantly higher in APA and IHA than in PH patients; there were more patients with microalbuminuria in the APA and IHA than in the PH group (P = 0.007). Among the hypertensive patients with a preserved GFR, those with APA or IHA have a higher UAE rate than comparable PH patients. Thus, hypertension because of excess autonomous aldosterone secretion features an early and more prominent renal damage than PH.

Albuminuria↗

Changes in extracellular matrix in subcutaneous small resistance arteries of patients with primary aldosteronism.

CONTEXT AND OBJECTIVE: It has been previously demonstrated that aldosterone may possess a strong profibrotic action in vitro and in animal models of genetic or experimental hypertension. Our aim was to evaluate whether such a profibrotic action is present also in the human microcirculation. DESIGN AND PATIENTS: We investigated 13 patients with primary aldosteronism, seven patients with essential hypertension, and 10 normotensive controls. All subjects were submitted to a biopsy of gluteal sc fat tissue. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media to internal lumen ratio was measured. MAIN OUTCOME MEASURES: The total collagen content within the tunica media was detected (Sirius red staining and image analysis), and collagen subtypes were evaluated using polarized light microscopy; under this condition thicker type I collagen fibers appear orange or red, whereas thinner type III collagen fibers are yellow or green. RESULTS: Tunica media to internal lumen ratio was significantly increased in primary aldosteronism and in essential hypertension compared with normotensive controls. Clinic blood pressure values were similar in primary aldosteronism and in essential hypertension, and greater than in normotensive controls. Normotensive controls had less total and type III collagen (3.23 +/- 0.58 and 1.60 +/- 0.22%, respectively) in respect to the two hypertensive groups (P < 0.001). Total collagen and type III vascular collagen were significantly greater in primary aldosteronism (total collagen, 8.17 +/- 1.38%; type III collagen, 6.06 +/- 0.74%; P < 0.05) than in essential hypertension (total collagen, 6.84 +/- 1.15%; type III collagen, 5.25 +/- 0.80%). CONCLUSIONS: Our results indicate that, in small resistance arteries of patients with primary aldosteronism, a pronounced fibrosis may be detected, even more evident than in blood-pressure-matched patients with essential hypertension.

Adipose Tissue↗

Small artery remodeling in hypertension and diabetes.

The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small artery smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, whereas in some secondary forms of hypertension and in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling may be detected. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients. Various antihypertensive drugs seem to have different effects on vascular structure. A complete normalization of small resistance artery structure was demonstrated in hypertensive patients, after prolonged and effective therapy with angiotensin-converting enzyme inhibitors, angiotensin II-receptor blockers, and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard.

Arteries↗

Headache: Prevalence and relationship with office or ambulatory blood pressure in a general population sample (the Vobarno Study).

UNLABELLED: The association of headache and arterial hypertension is still controversial, although headache is usually considered a symptom of hypertension. The aim of this study is to evaluate the prevalence of headache in a general population sample and the relationship with arterial hypertension, as diagnosed by office measurements and ambulatory monitoring of blood pressure (BP). PATIENTS AND METHODS: In the randomized sample of the Vobarno population, 301 subjects (126 males, 175 females, age range 35-50 years) underwent a structured standardized headache questionnaire, office and 24-h ambulatory BP monitoring. RESULTS: Prevalence of lifetime headache and of migraine was greater in females than in males. Office and 24-h BP values did not differ between subjects without headache and subjects with headache. No differences in headache prevalence (58% vs 55%), migraine prevalence (32% vs 28%) and use of analgesic drugs in the presence of headache (82% vs 78%) were observed between hypertensive patients (93.5% newly diagnosed, 6.5% treated) and normotensive subjects. CONCLUSIONS: In a general population sample, hypertension (diagnosed by office and/or 24-h BP) is not associated with headache.

Adult↗

Lack of prognostic role of endothelial dysfunction in subcutaneous small resistance arteries of hypertensive patients.

OBJECTIVE: The presence of endothelial dysfunction in the coronary circulation or in the brachial artery has been found to be associated with a greater incidence of cardiovascular events. However, no data are presently available about the prognostic role of endothelial dysfunction in human small resistance arteries. DESIGN AND METHODS: Ninety subjects were included in the present study. They were: 10 normotensive subjects, 36 patients with essential hypertension, 10 patients with phaeochromocytoma, 11 patients with primary aldosteronism, 10 patients with renovascular hypertension, and 13 normotensive patients with non-insulin-dependent diabetes mellitus (NIDDM). All subjects were submitted to a biopsy of subcutaneous fat from the gluteal or the anterior abdominal region. Small resistance arteries were dissected and mounted on an isometric myograph, and the concentration-response curves to acetylcholine (from 10 to 10 mol/l) (endothelium-dependent vasodilatation) and sodium nitroprusside (from 10 to 10 mol/l) (endothelium-independent vasodilatation) after precontraction of the vessels with norepinephrine were evaluated. The subjects were re-evaluated (by clinical visits or telephone interviews) after an average follow-up time of 5.5 years. RESULTS: Twenty-nine subjects had a documented fatal or non-fatal cardiovascular event (5.87%/year). The endothelium-dependent vasodilatation in the subcutaneous small arteries was similar in subjects with or without cardiovascular events. Also, endothelium-independent vasodilatation to sodium nitroprusside was similar in the two groups. Similar results were obtained by subdividing patients in the different subgroups (essential hypertension, secondary hypertension, etc.). CONCLUSIONS: Our results indicate that endothelial dysfunction in the microcirculation does not predict cardiovascular events. It is possible that a prognostic role of endothelial dysfunction may be observed when other vascular districts prone to atherosclerosis are evaluated, or it might be detected only in patients at low to medium cardiovascular risk, in whom endothelial dysfunction is less advanced.

Acetylcholine↗

Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus.

Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.

Adult↗

Determination of arterial compliance using blood pressure waveform analysis with the CR-2000 system: Reliability, repeatability, and establishment of normal values for healthy European population--the seven European sites study (SESS).

BACKGROUND: We determined the reliability and repeatability of measurements of arterial compliance (AC) and gender- and age-specific normal ranges for a healthy European population. METHODS: Three hundred eight healthy volunteers from seven sites were evaluated. Two measurements were taken during the first visit, repeated on a second visit 1 to 4 weeks later. We used the HDI/PulseWave CR-2000 for measurements of AC. RESULTS: Intravisit measurements, taken 5 min apart, differed by less than 3% (range, 0.36% to 2.97%). All intervisit measures differed by less than 4% (range, 0.24% to 3.67%); none of these differences was statistically significant. All correlation coefficients for pairs of AC parameters measured 5 min apart at the same visit were significant at P < .0001. Paired AC parameters at visit 1 and 2 were highly correlated (P < .0001). Repeated measures GLM (general linear model) failed to detect a significant association between either of the AC parameters and visit (first or second), time (first or second measure at the same visit), and visit-by-time (the interaction of the two preceding factors), suggesting that order of measure had no effect on the final value. Analysis of reliability was used to develop a strictly parallel model estimate of unbiased reliability. Both intravisit and intervisit estimates of reliability indicate good repeatability of measure and were significant (P < .0001). The AC values were found to differ significantly by age group, with an inverse association between each of the AC parameters and age group. CONCLUSIONS: Measurement of the arterial waveform with the CR-2000 system is highly reproducible in healthy subjects.

Adolescent↗

Effects of olmesartan and enalapril at low or high doses on cardiac, renal and vascular interstitial matrix in spontaneously hypertensive rats.

We have evaluated the effects of different doses of an angiotensin-converting enzyme (ACE) inhibitor, enalapril (ENA) and of an angiotensin II type 1 receptor blocker olmesartan (OLM), on extracellular matrix of the heart, kidney, aorta and mesenteric artery of spontaneously hypertensive rats (SHR). Forty SHR and eight Wistar-Kyoto controls (WKY) were included in the study. Eight SHR were treated with high-dose OLM 15 mg/kg per day, eight with high-dose ENA 25 mg/kg per day, eight with low-dose OLM 1 mg/kg per day and eight with low-dose ENA (2 mg/kg per day). Eight SHR and eight WKY were kept untreated as controls. Treatment was from age 4 to 12 weeks. Systolic blood pressure (SBP) was measured non-invasively every week. The left ventricular weight to body weight (RLVM) was measured, and the cardiac, aortic and glomerular interstitial collagen content was evaluated using Sirius red staining and image analysis. Mesenteric small arteries were dissected and mounted on a micromyograph, and the media:lumen ratio (M/L) was calculated. Collagen subtypes were evaluated by polarized light microscopy. The SHR treated with high-dose OLM or ENA showed a normalization of SBP. The RLVM was significantly increased in untreated SHR compared with untreated WKY, whereas significantly lower values were observed in the groups of SHR treated with high-dose OLM or ENA. A significant increase in cardiac and glomerular collagen content was observed in untreated SHR. Both high- or low-dose OLM and ENA normalized collagen content in the heart and the kidney. Both high-dose OLM and high-dose ENA normalized M/L ratio; however, OLM proved to be more effective than ENA in normalizing collagen pattern. In fact, aortic collagen content was normalized by both high-dose and low-dose OLM, but only by high-dose ENA. In conclusion, both OLM and ENA were significantly and equally effective in the prevention of cardiac and renal damage in SHR, whereas OLM was more effective than ENA in terms of effects on vascular extracellular matrix.

Animals↗

Effects of nifedipine GITS 20 mg or enalapril 20 mg on blood pressure and inflammatory markers in patients with mild-moderate hypertension.

OBJECTIVE: Calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and other drug classes either alone or in combination have been recommended for the treatment of hypertension. Nifedipine gastrointestinal therapeutic system (GITS) 20 mg is a new low-dose formulation with an improved tolerability. The aim of the present study was to compare the effects of nifedipine GITS 20 mg and enalapril 20 mg on blood pressure and circulating adhesion molecules in hypertensive patients. METHODS: This randomized, double-blind, multicentre trial compared the blood pressure lowering effects of a 12-week treatment of nifedipine GITS 20 mg vs enalapril 20 mg in 264 patients with mild-to-moderate hypertension. RESULTS: Nifedipine GITS 20 mg induced a reduction of clinic blood pressure, which was similar to that observed with enalapril 20 mg. Nifedipine GITS and enalapril lowered mean sitting diastolic blood pressure by 11.8 and 12.4 mmHg, respectively, while systolic blood pressure was reduced by 15.3 and 16.3 mmHg, respectively. Ambulatory blood pressure monitoring-derived blood pressure data showed similar results in both groups without any statistically significant differences between treatments. Both enalapril and nifedipine tended to reduce ICAM-1 and E-selectin, while only nifedipine reduced von Willebrand factor. Both treatments were well tolerated. CONCLUSIONS: Our findings demonstrate a similar antihypertensive effectiveness of a low dose (20 mg) of nifedipine GITS in comparison with a standard dose of enalapril (20 mg). Given its clinical efficacy and good tolerability, low-dose nifedipine GITS may be considered a valuable treatment option for hypertensive patients.

Adult↗

Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension.

An enormous number of studies in the last two decades have been devoted to investigating the role of the endothelium in cardiovascular diseases. Nonetheless, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, molecular genetic tests and invasive and non-invasive tools with and without pharmacological and physiological stimuli have been introduced. Furthermore newer pharmacological tools have been proposed. However, the application of these methodologies should fulfil a number of requirements in order to provide conclusive answers in this area of research. Thus, the most relevant methodological issues in the research on endothelial function and dysfunction are summarized in this paper.

Endothelium, Vascular↗

Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension.

Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with atherosclerosis and is therefore held to be an early feature in atherogenesis. However, the mechanisms by which endothelial dysfunction occurs in smoking, dyslipidaemia, hyperhomocysteinaemia, diabetes mellitus, arterial hypertension, cerebrovascular diseases, coronary artery disease and heart failure are complex and heterogeneous. Recent data indicate that endothelial dysfunction is often associated with erectile dysfunction, which can precede and predict cardiovascular disease in men. This paper will provide a concise overview of the mechanisms causing endothelial dysfunction in the different cardiovascular risk factors and disease conditions, and of the impact of the intervention measures and treatments.

Cardiovascular Diseases↗

Small artery structure and hypertension: adaptive changes and target organ damage.

Hypertension is known to be associated with an increase in the wall/lumen ratio (W/L) of the resistance arteries. Growth, eutrophic remodelling and changes in arterial distensibility can all contribute to an increase W/L. Wall stress may stimulate growth, whereas remodelling and/or reduced distensibility may be the result of prolonged contraction. Impaired or overwhelmed pressure-induced myogenic constriction, causing increased wall stress, may explain the small artery growth seen in diabetes and secondary hypertension, respectively. We find that small artery growth is a greater predictor of cardiovascular events than an increased W/L.

Adaptation, Physiological↗

Effects of candesartan cilexetil and enalapril on inflammatory markers of atherosclerosis in hypertensive patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: Circulating adhesion molecules may have a prognostic significance as markers of endothelial damage. Drugs which inhibit the renin-angiotensin system may be effective in reducing circulating or tissue adhesion molecules, albeit data available are scarce. The aim of the study was to investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor, enalapril and a highly selective angiotensin receptor blocker, candesartan cilexetil, on circulating adhesion molecules in a large sample of patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was comparative, multicenter, randomized and double blind, with two parallel groups. PATIENTS AND METHODS: NIDDM patients with a diagnosis of mild (grade 1) essential hypertension were included in the study, at the end of a 2-week placebo run-in period. The primary end-point of the study was to evaluate changes of intercellular adhesion molecule-1 (ICAM-1) plasma levels during treatment. The secondary end-points were: changes in vascular cells adhesion molecule-1 (VCAM-1), von Willebrand factor (vWF), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) circulating levels and of urinary albumin excretion rate (AER) as well; 129 patients were randomized: 66 in the candesartan group and 63 in the enalapril group, 118 of them completed the scheduled 24-week treatment period. RESULTS: Candesartan and enalapril equally reduced circulating level of ICAM-1 and exerted comparable effects on changes of other adhesion molecules and coagulation factors. A similar blood pressure-lowering effect was observed with the two drugs (candesartan: from 148/90 +/- 11/8 to 132/82 +/- 12/7 mmHg, P < 0.01, enalapril: from 148/91 +/- 12/8 to 131/85 +/- 14/6 mmHg, P < 0.01). Candesartan was more effective than enalapril in the reduction of albuminuria (P < 0.05 between treatments), although urinary protein excretion can be considered normal in the majority of patients. The two drugs were comparable in terms of adverse events reported. CONCLUSION: Candesartan and enalapril showed similar effects on blood pressure and on circulating adhesion molecules. In this study urinary protein excretion was reduced more by candesartan.

Adult↗

Prevalence of fetal-type smooth muscle cells in the media of microvessels from hypertensive patients.

Significant structural and functional changes in smooth muscle cells (SMCs) of microvessels (diameter 30 to 300 microm) occur in hypertension. However, in microvessels of hypertensive patients, the differentiation pattern of SMCs underlying such changes remains undefined. To analyze the differentiation pattern of SMCs (adult, postnatal, or fetal), 49 muscle biopsies (rectus abdominis) were analyzed: 16 from children (aged 11 months to 11 years), 15 from normotensive adults (aged 55 to 74 years), 18 from hypertensive adults (aged 55 to 74 years). Transverse cryosections of specimens were studied by immunocytochemistry using monoclonal antibodies SM-E7 and NM-F6, which recognize smooth muscle myosin heavy chain (MyHC) and A(pla1)-like nonmuscle MyHC, respectively. The total number of microvessels was assessed via SM-E7 staining. The number of NM-F6 positive (fetal-type SMC) or negative (adult-type SMC) microvessels was assessed. The number of microvessels per area unit was considerably lower (P<0.0005) in normotensive adults (0.22+/-0.17) than in children (0.98+/-0.61). Even more significant reduction was found in hypertensive adults compared with control adults (P=0.013) and children (P<0.0005). The qualitative immunocytochemistry analysis by NM-F6 revealed 2 differentiation patterns of the media layer of microvessels: positive or negative. In hypertensive subjects, the percentage of microvessels positive to NM-F6 was 49.8+/-35.6%, close to that found in children (50.6+/-12.6%), whereas in normotensive subjects it was significantly lower (24.4+/-21.1%). The following conclusions were drawn. (1) The medial layer of microvessels is heterogeneous in terms of SMC differentiation. (2) In hypertension, a prevalence of fetal-type SMCs takes place in microvessels, resembling that of children. Compared with children, a rarefaction of microvessels is present in normotensive adults that is even more remarkable in hypertensive adults.

Aged↗

Left ventricular concentric geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients.

Left ventricular (LV) mass and geometry predict risk for cardiovascular events in hypertension. Regression of LV hypertrophy (LVH) may imply an important prognostic significance. The relation between changes in LV geometry during antihypertensive treatment and subsequent prognosis has not yet been determined. A total of 436 prospectively identified uncomplicated hypertensive subjects with a baseline and follow-up echocardiogram (last examination 72+/-38 months apart) were followed for an additional 42+/-16 months. Their family doctor gave antihypertensive treatment. After the last follow-up echocardiogram, a first cardiovascular event occurred in 71 patients. Persistence of LVH from baseline to follow-up was confirmed as an independent predictor of cardiovascular events. Cardiovascular morbidity and mortality were significantly greater in patients with concentric (relative wall thickness > or =0.44) than in those with eccentric geometry (relative wall thickness <0.44) in patients presenting with LVH (P=0.002) and in those without LVH (P=0.002) at the follow-up echocardiogram. The incidence of cardiovascular events progressively increased from the first to the third tertile of LV mass index at follow-up (partition values 91 and 117 g/m2), but for a similar value of LV mass index it was significantly greater in those with concentric geometry (OR: 4.07; 95% CI: 1.49 to 11.14; P=0.004 in the second tertile; OR: 3.45; 95% CI: 1.62 to 7.32; P=0.001 in the third tertile; P<0.0001 in concentric versus eccentric geometry). Persistence or development of concentric geometry during follow-up may have additional prognostic significance in hypertensive patients with and without LVH.

Adolescent↗