Biomedical subjects

A C Pessina

Publications and source records attributed to A C Pessina.

At least 19 recordsLinked to original sources

PubMed2006

Glomerular hyperfiltration predicts the development of microalbuminuria in stage 1 hypertension: the HARVEST.

Factors related to the development of microalbuminuria in hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration precedes the development of microalbuminuria in hypertension. We assessed 502 never-treated subjects screened for stage 1 hypertension without microalbuminuria at baseline and followed up for 7.8 years. Creatinine clearance was measured at entry. Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up until subjects developed sustained hypertension needing antihypertensive treatment. Subjects with hyperfiltration (creatinine clearance >150 ml/min/1.73 m2, top quintile of the distribution) were younger and heavier than the rest of the group and had a greater follow-up increase in urinary albumin than subjects with normal filtration (P<0.001). In multivariable linear regression, creatinine clearance adjusted for confounders was a strong independent predictor of final urinary albumin (P<0.001). In multivariable Cox regression, patients with hyperfiltration had an adjusted hazard ratio for the development of microalbuminuria based on at least one positive measurement of 4.0 (95% confidence interval (CI), 2.1-7.4, P<0.001) and an adjusted hazard ratio for the development of microalbuminuria based on two consecutive positive measurements of 4.4 (95% CI, 2.1-9.2, P<0.001), as compared with patients with normal filtration. Age, female gender, and 24 h systolic blood pressure were other significant predictors of microalbuminuria. In conclusion, stage 1 hypertensive subjects with glomerular hyperfiltration are at increased risk of developing microalbuminuria. Early intervention with medical therapy may be beneficial in these subjects even if their blood pressure falls below normal limits during follow-up.

Adult↗

PubMed2006

Effect of doxazosin on oxidative stress related proteins in essential hypertensive patients.

The role of oxidative stress in the pathophysiology of hypertension has stimulated the investigation of strategies to reduce oxidative stress via antioxidant defenses. Using a molecular biology approach, we report, in essential hypertensive patients, the effect of doxazosin treatment on the mononuclear cell gene and protein expression of two major elements in the oxidative stress and vascular remodeling-related pathways: p22(phox) and PAI-1. Ten essential hypertensive patients were treated with Doxazosin (4 mg/day) for two weeks (EH + D) and compared with ten untreated hypertensive patients (EH) and ten normotensive subjects (C). In EH p22(phox) and PAI-1 mRNA and protein level was increased compared with C. In EH + D, doxazosin reduced p22(phox) and PAI-1 gene and protein expression, which was similar to that of C. These results demonstrate for doxazosin an inhibitory effect on oxidative stress related proteins at gene and protein level, which confirms at molecular level a powerful antioxidant potential for this agent that could translate, in the long term, into a powerful antiatherosclerotic effect.

Adult↗

PubMed2006

Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients.

OBJECTIVE: To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non-CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P = 0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.

Adiponectin↗

PubMed2005

Clinical efficacy and tolerability of alpha-blocker doxazosin as add-on therapy in patients with hypertension and impaired glucose metabolism.

BACKGROUND AND AIM: The aim of this trial was to evaluate the effect of doxazosin as add-on therapy in patients with hypertension not adequately controlled on current antihypertensive therapy, and impaired glucose metabolism. The effect of doxazosin administered as add-on therapy was to be considered significant both from clinical and statistical viewpoints if the proportion of patients with adequate control of blood pressure (BP<130/85 mmHg) would be at least 30% after 16 weeks of combined therapy. METHOD AND RESULTS: It was an open, multicenter phase IV study, lasting 19 weeks: 3-week qualifying/placebo run-in period+16-week dose titration/add on therapy period, involving 264 out-patients (158 m and 106 f; mean age+/-SD: 60.9+/-8.6 years; mean BMI+/-SD: basal 29.5+/-5.1, final 30.2+/-4.6) with blood pressure still >130/85 mmHg in spite of the antihypertensive treatment (ACE inhibitors 44%, AT II antagonists 21%, Ca antagonists 12%, other drugs 8%, polytherapy 15%) and affected by type 2 diabetes (n=219), impaired fasting glucose (IFG; n=16) or impaired glucose tolerance (IGT; n=29). Following a run-in, 3-week qualifying phase during which placebo was added to ongoing antihypertensive treatment, 16-week treatment with doxazosin was added at dosages from 1 up to 8 mg/day. Main outcome measures were: the percentage of patients with blood pressure <130/85 mmHg at the end of treatment; the effects of the combination therapy on glyco-lipidic metabolism: fasting plasma glucose, fasting insulin, glycated hemoglobin, insulin resistance (HOMA-R), plasma lipids; and the effect on the 10-year CHD risk (Framingham equation). RESULTS: 35% of patients were responsive (BP<130/85 mmHg) to add-on treatment with doxazosin (CI 90%: 30.3%-40.4%; P<0.05, stat. an. intention to treat). During the run-in phase with placebo, mean SBP/DBP (+/-SD) decreased from 155.6+/-13.2/91.8+/-6.8 mmHg (Week -3) to 151.9+/-12.9/90.1+/-7.2 mmHg (Week -1) and to 151.2+/-11.5/90.1+/-6.9 mmHg (Week 0). During add-on treatment with doxazosin, mean SBP/DBP (+/-SD) further decreased to 144.9+/-15.2/86.3+/-8.3 mmHg (Week 4), 139.7+/-15.3/83.4+/-7.9 mmHg (Week 8), 135.5+/-14.3/81.7+/-7.6 mmHg (Week 12) and 136.4+/-14.5/81.0+/-7.0 mmHg (Week 16). Overall, mean BP changes reached a plateau of about -15 mmHg (SBP) and -9 mmHg (DBP) after 16 weeks of treatment; at each visit the mean decreases from baseline were statistically significant. The following mean values of metabolic parameters were reduced during the study: fasting plasma glucose (-4.1mg/dl; -2.8%), fasting insulin (-2 microU/ml; -12.3%; P<0.05), glycated hemoglobin (-0.12%; -1.7%), HOMA-R (-1.03; -18.2%; P<0.05), total cholesterol (-1.85 mg/dl; -1.1%), LDL cholesterol (-1.35 mg/dl; -0.8%) and triglycerides (-5.64 mg/dl; -2.4%); mean HDL cholesterol increased (+1.79 mg/dl; +3.9%; P<0.01). At the end of study treatment, the percentage of patients with lab values returned within normal ranges, in comparison with basal values, was statistically significant (P<0.05) for the following parameters: fasting plasma glucose (6.3%), fasting insulin (7.5%), LDL cholesterol (6.0%). Ten-year CHD risk (+/-SD) decreased from 16.4+/-7.8% to 13.6+/-7.4% (final vs. basal: -2.87+/-3.9; -17%; P<0.01). Six patients (2.3%) reported 8 adverse drug reactions: dizziness (3), edema (2), headache (2), asthenia (1). In one out of these 6 patients, in whom doxazosin was associated to the ACE inhibitor quinapril, adverse reaction (peripheral edema) led to treatment withdrawal. CONCLUSION: In patients not responsive to antihypertensive treatment and concomitantly affected by impaired glucose metabolism, achievement of target BP was obtained in more than one third of cases after 16-week add-on treatment with doxazosin. Changes in glyco-lipidic parameters and reduction of 10-year CHD risk observed during the study, although of moderate extent, confirm the overall favourable effect of antihypertensive combinations including doxazosin.

Adrenergic alpha-Antagonists↗

PubMed2005

Homocysteine-lowering treatment in coronary heart disease.

Homocysteine (Hcy) is a sulphur-containing amino acid product of methionine's metabolism. Hyperhomocysteinemia (HHcy) is considered an independent risk factor for cardiovascular (CV) disease, at least in high-risk patients. In fact, evidence indicates that although mild HHcy may be regarded as a minor risk factor for CHD in low-risk patients, it can play a role in triggering new events in patients with known CHD, also by interacting with the "classical" CV risk factors. This is of much interest because HHcy represents a correctable risk factor, inasmuch vitamin supplementation as has been shown to effectively lower total homocysteine plasma levels (tHcy). While case-control and cross-sectional studies have consistently demonstrated an association of HHcy with CV disease, prospective studies have given conflicting results. Moreover, the effect of the homocysteine-lowering treatment in preventing CV events is still under debate. Thus, it remains unclear which patients should be screened for HHcy and which ones should be treated to lower tHcy. In this paper we shall report and discuss knowledge on the potential role of HHcy in the development of CHD and on the benefits due to tHcy-lowering treatment with vitamins.

Adult↗

PubMed2003

Total cholesterol and mortality in the elderly.

OBJECTIVE: To evaluate, at a population level, whether total cholesterol (TC) is a risk factor of mortality. To verify whether or not this is true for both genders. DESIGN: Population-based, long-lasting, prospective study. SETTING: Institutional epidemiology in primary care. SUBJECTS: A total of 3257 subjects aged 65-95 years, recruited from Italian general population. INTERVENTION: None. MAIN OUTCOME MEASURES: Total cholesterol was measured, analysed as a continuous variable and then divided into quintiles and re-analysed. For each quintile, the multivariate relative risk (RR) of mortality adjusted for confounders was calculated in both genders. Stratification of mortality risk by TC quintiles, body mass index and cigarette smoking was also performed in both genders. RESULTS: Total cholesterol levels directly predicted coronary mortality in men [RR being in the fifth rather than in the first quintile: 2.40 (1.40-4.14)] and any other mortality in women. It also inversely predicted miscellaneous mortality in both genders. This trend was more evident when low cholesterol was associated with malnutrition or smoking. CONCLUSIONS: High TC remains a strong risk factor for coronary mortality in elderly men. On the other hand, having a very low cholesterol level does not prolong survival in the elderly; on the contrary, low cholesterol predicts neoplastic mortality in women and any other noncardiovascular mortality in both genders.

Aged↗

PubMed2002

Weak effect of hypertension and other classic risk factors in the elderly who have already paid their toll.

The aim of the CASTEL, a population-based (n=3282) prospective study which began 14 years ago, was to identify those items which had a prognostic impact in the elderly, and to evaluate whether the typical cardiovascular risk factors, particularly arterial hypertension, play a role after the age of 65 years. Initial screening, final follow-up and annual detection of mortality were performed. Mantel-Hanszel approach and multivariate Cox model were used for statistics. Cardiovascular mortality was 23.3% in normotensive, 23.3% in borderline, and 25% in the sustained hypertensive subjects (insignificant difference). In women, the incidence of stroke and coronary artery disease weakly depended on pulse pressure. Historical stroke and myocardial infarction predicted cardiovascular mortality in women; diabetes, uricaemia and high heart rate in men. In the very old, the predictors were less numerous, and blood pressure was not a predictor whatsoever; pulse blood pressure and murmurs at the neck were especially predictive in women, historical heart failure, proteinuria and tachycardia in men, historical stroke and myocardial infarction, pulmonary disease, left ventricular hypertrophy, diabetes and uricaemia in both genders. The elderly have a different cardiovascular risk pattern compared to younger people. Hypertension is not a predictor of coronary and stroke mortality. Prognosis depends on pulse pressure rather than on the label 'hypertension'. Hypercholesterolaemia is not a risk factor. This could simply indicate that elderly persons are the survivors in a population where significant mortality has already made its mark, eliminating those with the worst risk pattern. The two genders have a different risk profile due to sex-specific susceptibility to risk factors.

Aged↗

PubMed2002

Pulse pressure and coronary mortality in elderly men and women from general population.

The aim of this work was to evaluate whether pulse pressure (PP) in elderly people is a better predictor of coronary mortality than systolic and diastolic blood pressure taken alone. For this aim, 3282 elderly subjects aged >or=65 years were studied in a population-based frame. Blood pressure was repeatedly measured and averaged; historical data, anthropometrics, blood tests and 14-year coronary mortality were recorded. Statistics included analysis of covariance, Cox analysis and bivariate vectorial analysis. Coronary mortality in women was predicted by PP (1.01 excess risk/mm Hg PP) and was significantly higher in the 3rd than in the 1st tertile of PP (relative risk 2.90); neither systolic nor diastolic pressure taken alone influenced mortality. When systolic and diastolic pressures were both entered into a Cox model, the former had a positive and the latter a negative effect on survival, confirming a prognostic role of PP. For any given level of systolic pressure, mortality was inversely associated with diastolic pressure. Finally, the mean vector representing both systolic and diastolic pressures of non-surviving women was characterised by higher systolic and lower diastolic components than in non-surviving. No significant trend of mortality in relation to either systolic blood pressure or PP was observed in men. In conclusion, the combination of systolic and diastolic pressure called PP is an independent predictor of coronary mortality in elderly females, and a better predictor than systolic or diastolic pressure alone.

Aged↗

PubMed2002

Nebivolol vs amlodipine as first-line treatment of essential arterial hypertension in the elderly.

The antihypertensive efficacy of nebivolol and amlodipine and their tolerability were compared in a multicentre, randomized, active-controlled, double-blind parallel-group trial in elderly patients with mild to moderate essential arterial hypertension. One hundred and eighty-four subjects aged > or = 65 years were screened. After a run-in phase of 4 weeks, only 168 of these were randomized with either nebivolol 2.5-5 mg daily (n = 81) or amlodipine 5-10 mg daily (n = 87) over a period of 12 weeks. The response rate to treatment and the changes of sitting diastolic blood pressure (BP) at week 12 were similar between the two groups. A lower sitting systolic BP (SBP) was detected with amlodipine at week 4 (p < 0.05) and at week 8 (p < 0.05). Standing BP showed no changes between the two groups; only SBP was lower with amlodipine at week 8 (p < 0.05). Heart rate was lower at all treatment visits with nebivolol (p < 0.001). The incidence of adverse events was no different between the two groups; however the incidence of headache and ankle oedema was significantly higher with amlodipine (p < 0.05). In elderly subjects with essential hypertension, the antihypertensive efficacy of nebivolol and amlodipine was similar. Both drugs were well tolerated, although amlodipine was accompanied by higher incidence of drug-related adverse events.

Aged↗

PubMed2001

Left ventricular contractile performance in the early stage of hypertension in humans.

The aim of the present study was to assess how cardiac structural changes contribute to increasing left ventricular pump function during exercise in subjects with mild hypertension. In 23 young male subjects with mild hypertension and 12 male normotensive control subjects, left ventricular function was measured echocardiographically using the fractional shortening/ meridional stress relationship at rest and during longlasting exercise at the anaerobic threshold. Mean exercise duration and intensity were 61 (SEM 1.7) min and 71.3 (SEM 2.5)% VO2max (maximal oxygen uptake), respectively, in the hypertensive subjects, and 63 (SEM 1.5) min and 75.7 (SEM 2.2)% VO2max, respectively, in the normotensive subjects (all differences= n.s.). Left ventricular fractional shortening was measured both at the endocardium and at the midwall. In the hypertensive subjects the endocardial fractional shortening, predicted on the basis of the shortening/stress relationship in the normotensive controls, overestimated midwall fractional shortening throughout rest (P=0.04) and exercise (P=0.004). To study how an increase in left ventricular wall thickness contributed to increasing ejection performance during exercise, the hypertensive subjects were divided according to whether their relative wall thickness was less than 0.35 or equal to or greater than 0.35. Subjects with relative wall thicknesses equal to or greater than 0.35 had a depressed myocardial contractility at rest (P=0.0001). During exercise they increased their stroke volume and cardiac output adequately through an increase in ejection performance, while myocardial contractility remained subnormal (P < 0.0001). In conclusion, the present results indicated that in mildly hypertensive subjects an increased left ventricular wall thickness is crucial in preserving left ventricular pump function during exercise.

Adult↗

PubMed2001

Predictors of stroke mortality in elderly people from the general population. The CArdiovascular STudy in the ELderly.

Stroke occurs particularly frequently in elderly people and, being more often disabling than fatal, entails a high social burden. The predictors of stroke mortality have been identified in 3282 subjects aged > or = 65 years, taking part in the CArdiovascular STudy in the ELderly (CASTEL), a population-based study performed in Northeast Italy. Historical and clinical data, blood tests and 14-year fatal events were recorded. Continuous items were divided into quintiles and, for each quintile, adjusted relative risk (RR) with 95% confidence intervals [CI] was derived from multivariate Cox analysis. Age, historical stroke (RR: 5.2; 95% CI: 3.18-8.6) and coronary artery disease (RR: 1.38; CI: 1.18-2.1), atrial fibrillation (RR: 2.40; CI: 1.42-4.0), arterial hypertension (RR: 1.33; CI: 1.15-1.76), systolic blood pressure > or = 163 mmHg (RR: 1.84; CI: 1.20-2.59), pulse pressure > or = 74 mmHg (RR: 1.50; CI: 1.13-2.40), cigarette smoking (RR: 1.60; CI: 1.03-2.47), electrocardiographic left ventricular hypertrophy (RR: 1.72; CI: 1.10-2.61), impaired glucose tolerance (IGT, RR: 1.83; CI: 1.10-3.0), uric acid (UA) > 0.38 mmol/l (RR: 1.61; CI: 1.14-2.10), serum potassium > or = 5 mEq/l (RR: 1.70; CI: 1.24-2.50) and serum sodium < or = 139 mEql/l (RR: 1.34; 1.10-2.10) increased the risk of stroke. In the CASTEL, stroke was the first cardiovascular cause of death. Some independent predictors usually unrelated to stroke mortality (namely pulse pressure, pre-diabetic IGT, UA and blood electrolytes disorders) have been identified.

Aged↗

PubMed2001

Early signs of cardiac involvement in hypertension.

BACKGROUND: Whether abnormalities of diastolic function are the earliest cardiac change in hypertension is still a matter for dispute. The aim of this study was to assess whether left ventricular diastolic dysfunction is an early sign of cardiac involvement in hypertension. METHODS: In 578 young patients with stage I hypertension from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) and 101 normotensive control patients echocardiographic Doppler examination and ambulatory blood pressure monitoring were performed. RESULTS: Left ventricular mass, wall thickness, and relative wall thickness, adjusted for confounders, were greater in the hypertensive than in the normotensive patients (all P <.0001). After adjustment for confounders, the A-wave peak velocity was higher in the hypertensive patients (51.5 +/- 11.5 vs 43.4 +/- 8 cm/s, P <.001) as were A-wave velocity time integral (5.6 +/- 1.7 vs 4.6 +/- 1.3 cm, P =.01), total area (16.9 +/- 4.4 vs 15.6 +/- 3.1 cm, P =.04), and E-wave peak velocity (69.9 +/- 15.2 vs 67.5 +/- 13.3 cm/s, P =.03). All indexes of diastolic function were similar in the hypertensive subjects subdivided according to whether they had "white-coat" or sustained hypertension. Among the hypertensive subjects, age and heart rate were the strongest predictors of diastolic indexes, whereas ambulatory blood pressure explained only a marginal part of the E/A ratio, A-wave peak velocity, and the first one third total area ratio (P =.04, P =.02, and P =.05, respectively). Left ventricular mass and wall thickness were not associated with any Doppler index. When a clustering of diastolic indexes (E/A wave ratio, deceleration time, first one third of diastole, and peak E-wave-velocity) was used to identify subjects with diastolic dysfunction, no significant differences in either clinic or ambulatory blood pressure were observed between the group with diastolic dysfunction and the group with normal function. CONCLUSIONS: We conclude that the earliest signs of cardiac involvement in hypertension are left ventricular structural abnormalities. Left ventricular diastolic function is only marginally affected, even when multiple parameters of left ventricular filling are taken into account.

Adult↗

PubMed2001

Pulse pressure: an independent predictor of coronary and stroke mortality in elderly females from the general population.

The aim of this paper is to evaluate whether pulse pressure is an independent risk factor for coronary and stroke mortality in 3282 subjects (1281 males and 2001 females) aged +/- 65 years, taking part in the CArdiovascular STudy in the Elderly (CASTEL). After dividing subjects into tertiles of pulse pressure, adjusted relative risk (RR) and confidence intervals (CI) for 14-year coronary and stroke mortality was evaluated for each tertile. Among females, coronary mortality rate was 2.7% in the first tertile of pulse pressure, 4.7% in the second (RR 1.38, 95% CI [1.15-2.66]) and 6.2% in the third (RR 2, CI [1.20-3.51]). Stroke mortality was 3.6%, 4.1% (RR 1.23, CI [1.02-2.23]) and 8.3% (RR 2.27, CI [1.37-3.74]), respectively. This trend was recognizable in normotensive, borderline and sustained hypertensive women, where mortality increased with rising pulse pressure. No relationship was found between pulse pressure and mortality in males. In elderly women, pulse pressure was a good predictor of coronary and stroke mortality, even superior to the label of hypertension. No matter how any given pulse pressure level was obtained, it was more predictive of both coronary and cerebrovascular mortality than belonging to a normo- or hypertensive category.

Aged↗

PubMed2001

Efficacy, tolerability and influence on "quality of life" of nifedipine GITS versus amlodipine in elderly patients with mild-moderate hypertension.

OBJECTIVE: The main purpose of this study was to compare efficacy, tolerability and influence on quality of life (QOL) of nifedipine gastrointestinal therapeutic system (NI) 30-60 mg once a day vs amlodipine (AM) 5-10 mg once a day in elderly patients with mild-moderate hypertension. DESIGN: This was a randomized, double-blind, parallel-group, multicenter study. After a 2-week single-blind placebo run-in, patients were randomized to either NI 30 mg or AM 5 mg. Responders continued on the same dosage for 16 additional weeks, while non-responders were titrated to 60 mg NI or 10 mg AM. METHODS: Blood pressure was measured by mercury sphygmomanometer and efficacy equivalence of NI and AM tested by covariance analysis. Diastolic blood pressure (DBP) was the primary efficacy parameter, its baseline value being taken as covariate while centers effect and treatment interaction were included as fixed effects in the analysis model. The secondary efficacy variables systolic blood pressure (SBP) and scores for QOL were analyzed according to the same model. RESULTS: At the end of the study, overall mean DBPs, calculated as least-square means (LSMEANS), in the "by protocol" population were 87.5 mmHg for NI and 86.7 for AM (difference 0.8 mmHg with 90% CI -1.2 to 2.8 mmHg). In the "by intention to treat" (ITT) population LSMEANS were 87.6 mmHg for NI and 86.4 mmHg for AM (difference 1.2 mmHg with 90% CI -0.6 to 3.1 mmHg). SBP LSMEANS in the "by protocol" population were 147.7 mmHg for NI and 147.3 mmHg for AM (difference 0.3 mmHg, with 90% CI -3.7 to 4.3); corresponding values in the "by ITT" population were 148.0 mmHg for NI and 147.2 for AM (difference 0.8 mmHg, with 90% CI -2.8 to 4.6). Mean values for QOL parameters were not significantly different. A total of 173 episodes of adverse events were documented in 54 patients (26 NI and 28 AM), dropouts were 15 (20% of group) on NI and 21 (28%) on AM. CONCLUSIONS: NI 30-60 mg was shown to be as efficacious and safe as AM 5-10 mg in elderly patients with mild-moderate hypertension. QOL improved compared to baseline with no significant difference between the two drugs, thus confirming a positive class effect for calcium antagonists.

Aged↗

PubMed2001

Independent predictors of isolated clinic ('white-coat') hypertension.

BACKGROUND: Hypertension guidelines recommend 24 h ambulatory blood pressure (ABP) monitoring in hypertensive subjects with suspected isolated clinic hypertension (ICH). However, the pre-test probability of ICH based on the distribution of its independent predictors has not yet been estimated in hypertensive subjects with mildly elevated blood pressure. OBJECTIVE: To ascertain the independent predictors of ICH in mildly hypertensive subjects. METHODS: In the setting of the HARVEST-PIUMA collaboration, we studied 1564 subjects with hypertension stage I. At entry, all subjects were untreated and all underwent ABP monitoring and echocardiography. Diabetes, hypertension grade > I, renal failure or previous cardiovascular morbid events were exclusion criteria. Clinic BP was 143/92 mmHg (SD 9/5) and 24 h ABP was 128/81 mmHg (SD 10/8). RESULTS: Prevalence of ICH (daytime ABP < 130 mmHg systolic and 80 mmHg diastolic) was 10.4%. In a multivariate logistic regression analysis, sex (P = 0.002), smoking (P = 0.038) and clinic diastolic BP (P = 0.0002) were the sole independent predictors of ICH according to the following equation: Y = 2.6438 + 0.5128 x sex (0 = men; 1 = women) + 0.4543 x current smoking (0 = yes; 1 = no) - 0.0531 x clinic diastolic BP (mmHg) and P (probability of ICH) = exp(Y)/[1 + (exp(Y)]. Left ventricular (LV) mass at echocardiography was a further independent predictor (P = 0.002) of ICH according to the following equation: Y= 3.4343 + 0.4603 x sex + 0.5989 x current smoking - 0.0482 x clinic diastolic BP - 0.0312 x LV mass [g/height (m)2.7]. LV mass was greater (P < 0.01) in the group with ambulatory hypertension [42.3 g/height (m)2.7] than in that with ICH [39.2 g/height (m)2.7] and not dissimilar between the ICH group and a control group of 370 healthy normotensive subjects [38.1 g/height (m)2.7]. CONCLUSIONS: In untreated subjects with stage I hypertension, ICH is most frequent among women, nonsmokers and subjects with low clinic BP and smaller LV mass. These findings allow identification of subjects with indication to ABP monitoring because of suspected ICH.

Adult↗

PubMed2001

The endothelin-aldosterone axis and cardiovascular diseases.

The results of the Randomized Aldactone Evaluation Study (RALES) and of several experimental studies have indicated that excess aldosterone detrimentally affects cardiovascular morbidity and mortality by acting through both classical and non-classical mineralocorticoid receptors. The effects mediated through classical mineralocorticoid receptors entail enhanced sodium and water reabsorption, potassium loss and hypokalaemia, congestion, increased vascular resistance and hypertension. Those occurring through non-classical mineralocorticoid receptors located on myofibroblasts comprise cardiac hypertrophy and fibrosis, which may be due to a direct effect of aldosterone on collagen synthesis. Data obtained in primary aldosteronism patients demonstrated left ventricular hypertrophy, as well as changes in left ventricular filling that can be accounted for by cardiac fibrosis. Available clinical data indicate that in a considerable proportion of congestive heart failure (CHF) patients treated with angiotensin converting enzyme (ACE) inhibitors, aldosterone secretion can escape from blockade of the renin-angiotensin system, thus suggesting that additional mechanisms, besides angiotensin II, can play an important role in the regulation of aldosterone secretion. Compelling evidence indicates that endothelin (ET)-1 is overtly increased in severe CHF and thus is a likely candidate for the aldosterone 'escape' phenomenon in CHF. Endothelin-1 is expressed in the adrenal cortex, together with its receptor subtypes A (ETA) and B (ETB), and directly stimulates aldosterone secretion in different species, in humans by acting via both ETA and ETB receptor subtypes. Moreover, we have recently found that the novel endothelin peptide ET-1 (1-31), by acting as an ETA agonist, can also be involved in the regulation of growth of the adrenal cortex, as well as in the pathogenesis of Conn's adenoma. In this paper, we review the findings suggesting a relationship between activation of the ET-1 system, enhanced aldosterone secretion and cardiac fibrosis and discuss the implications of endothelin antagonism for cardiovascular disease.

Adrenal Cortex↗

PubMed2001

Hypertension and cerebrovascular diseases: a specific role of vascular protection for the prevention of dementia.

Despite the use of antihypertensive drugs, mortality (but not morbidity) from cerebrovascular diseases has been reduced significantly. As a consequence, an increasing number of patients suffer from recurring strokes and from the debilitating consequences of cerebrovascular diseases and develop progressive cognitive impairment. Its pathological substrates are regional alteration of cerebral perfusion, lacunae, white matter lesions, progressive cortical atrophy, even in the asymptomatic patient and in the absence of extracranial carotid artery stenosis. Lacunar infarction and white matter lesions are particularly frequent in the hypertensive diabetic patient. Lacunae and white matter lesions sometimes coexist and may favour the development of dementia in the hypertensive patient, through focal ischaemia, perivascular oedema, disruption of the blood-brain barrier, cerebral diaschisis and cortical deafferentation. Treatment with calcium channel blockers, angiotensin converting enzyme inhibitors and diuretics smooth the patchy hypoperfusion despite the fall in pressure. However, the time course and the extent of this effect vary according to the drug administered. In particular, only a calcium channel blocker increased perfusion of both cortical and subcortical areas, while diuretic treatment increased perfusion only after prolonged treatment, and this effect was limited to the cortical areas. Such differences may explain the discrepant results on risk reduction for dementia observed in large intervention trials.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Metabolic effects and safety profile of nebivolol.

Nebivolol, compared with classical beta-blockers, exerts a high selectivity for beta-adrenergic receptors and also reduces peripheral vascular resistance by modulating nitric oxide (NO) release. This dual mechanism of action leads to effective control of blood pressure at a low degree of beta-blockade and explains the lack of any interference with lipid metabolism. For the same reason, the tolerability profile of nebivolol is highly favorable compared with the classical beta-blockers, with less fatigue and dyspnea in hypertensive subjects, and with an improvement of functional capacity and exercise tolerance in patients with left ventricular dysfunction. Furthermore, contrary to atenolol and propranolol, nebivolol does not diminish specific airway conductance. Compared with other first-line antihypertensive agents, nebivolol was shown to be better tolerated than nifedipine and enalapril, and to have a positive effect on general wellbeing. Among the currently available antihypertensive drugs, nebivolol therefore appears to have a most alteractive safety and tolerability profile, which can be attributed to its NO-mediated effects allowing effective control of hypertension at a lower degree of beta-blockade than with first-generation beta-blockers.

Adrenergic beta-Antagonists↗