The cost-effectiveness of transcatheter aortic valve implantation: exploring the Italian National Health System perspective and different patient risk groups.

OBJECTIVES: To assess the cost-effectiveness (CE) of transcatheter aortic valve implantation (TAVI) in Italy, considering patient groups with different surgical risk. METHODS: A Markov model with a 1-month cycle length, comprising eight different health states, defined by the New York Heart Association functional classes (NYHA I-IV), with and without stroke plus death, was used to estimate the CE of TAVI for intermediate-, high-risk and inoperable patients considering surgical aortic valve replacement or medical treatment as comparators according to the patient group. The Italian National Health System perspective and 15-year time horizon were considered. In the base-case analysis, effectiveness data were retrieved from published efficacy data and total direct costs (euros) were estimated from national tariffs. A scenario analysis considering a micro-costing approach to estimate procedural costs was also considered. The incremental cost-effectiveness ratio (ICER) was expressed both in terms of costs per life years gained (LYG) and costs per quality adjusted life years (QALY). All outcomes and costs were discounted at 3% per annum. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess robustness of results. RESULTS: Over a 15-year time horizon, the higher acquisition costs for TAVI were partially offset in all risk groups because of its effectiveness and safety profile. ICERs were €8338/QALY, €11,209/QALY and €10,133/QALY, respectively, for intermediate-, high-risk and inoperable patients. ICER values were slightly higher in the scenario analysis. PSA suggested consistency of results. CONCLUSIONS: TAVI would be considered cost-effective at frequently cited willingness-to-pay thresholds; further studies could clarify the CE of TAVI in real-life scenarios.

Differential effect of everolimus on progression of early and late cardiac allograft vasculopathy in current clinical practice.

Randomized trials showed that mTOR inhibitors prevent early development of cardiac allograft vasculopathy (CAV). However, the action of these drugs on CAV late after transplant is controversial, and their effectiveness for CAV prevention in clinical practice is poorly explored. In this observational study we included 143 consecutive heart transplant recipients who underwent serial intravascular ultrasound (IVUS), receiving either everolimus or mycophenolate as adjunctive therapy to cyclosporine. Ninety-one recipients comprised the early cohort, receiving IVUS at weeks 3-6 and year 1 after transplant, and 52 the late cohort, receiving IVUS at years 1 and 5 after transplant. Everolimus independently reduced the odds for early CAV (0.14 [0.01-0.77]; p = 0.02) but it did not appear to influence late CAV progression. High-dose statins were found to be associated with reduced CAV progression both early and late after transplant (p ≤ 0.05). Metabolic abnormalities, such as high triglycerides, were associated with late, but not with early CAV progression. By highlighting a differential effect of everolimus and metabolic abnormalities on early and late changes of graft coronary morphology, this observational study supports the hypothesis that everolimus may be effective for CAV prevention but not for CAV treatment, and that risk factors intervene in a time-dependent sequence during CAV development.

Optimisation of therapeutic strategies for ST-segment elevation acute myocardial infarction: the impact of a territorial network on reperfusion therapy and mortality.

OBJECTIVE: To assess the clinical impact of a regional network for the treatment of ST-segment elevation myocardial infarction (STEMI). METHODS: All patients with STEMI (n = 1823) admitted to any of the hospitals of an area with one million inhabitants during the year 2002 (n = 858)-that is, before the network was implemented, and in 2004 (n = 965), the year of full implementation of the network, were enrolled in this study. The primary evaluation was in-hospital mortality. Secondary outcomes included the incidence of major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction, stroke and coronary revascularisation procedures over 1-year follow-up. RESULTS: Between 2002 and 2004, there was a major change in reperfusion strategy: primary angioplasty increased from 20.2% to 65.6% (p<0.001), fibrinolytic therapy decreased from 38.2% to 10.7% (p<0.001) and the rate of patients not undergoing reperfusion was reduced from 41.6% to 23.7% (p<0.001). In-hospital mortality decreased from 17.0% to 12.3% (p = 0.005), and this reduction was sustained at 1-year follow-up (23.9% in 2002 and 18.8% in 2004, p = 0.009). Similarly, the 1-year incidence of all MACCE was reduced from 39.5% in 2002 to 34.3% in 2004 (p = 0.01). CONCLUSIONS: Organisation of a territorial network for STEMI is associated with increased rates of reperfusion therapy and reduction of in-hospital and 1-year mortality.

Anaerobic biodegradation of pentachlorophenol in a fixed-film reactor inoculated with polluted sediment from Santos-São Vicente Estuary, Brazil.

This paper discusses the results of pentachlorophenol (PCP) anaerobic biodegradation in a horizontal-flow anaerobic immobilized biomass (HAIB) reactor operated under methanogenic and halophylic conditions. The system was inoculated with autochthonous microorganisms taken from a site in the Santos-São Vicente Estuary (state of São Paulo, Brazil) severely contaminated with PCP, phenolic compounds, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and heavy metals. The inoculum was previously enriched for methanogenesis activity by changing glucose concentrations and under halophylic condition. PCP was added to the HAIB reactor as sodium salt (NaPCP) at an initial concentration of 5 mg l(-1) and increased to 13, 15, and 21 mg l(-1). Organic matter removal efficiency ranged from 77 to 100%. PCP removal efficiency was 100%. Denaturing gradient gel electrophoresis profile showed changes in the structure of Bacteria domain, which was associated with NaPCP and glucose amendments. The diversity of Archaea remained unaltered during the different phases. Scanning electron microscope examinations showed that cells morphologically resembling Methanosarcina and Methanosaeta predominated in the biofilm. These cells were detected by fluorescence in situ hybridization with the Methanosarcinales (MSMX860) specific probe. The results are of great importance in planning the estuary's restoration by using anaerobic technology and autochthonous microorganisms for bioremediation.

Long term outcome after intracoronary beta radiation therapy.

OBJECTIVES: To determine the long term outcome after intracoronary beta radiation therapy (IRT). SETTING: Tertiary referral centre. METHODS: The rate of major adverse cardiac events (MACE) was retrospectively determined in 301 consecutive patients who were treated with IRT. MACE was defined as death, myocardial infarction, or any reintervention. Long term clinical outcome was obtained from an electronic database of hospital records and from questionnaires to the patients and referring physicians. Long term survival status was assessed by written inquiries to the municipal civil registries. RESULTS: The mean (SD) follow up was 3.6 (1.2) years. The cumulative incidence of MACE at six months was 19.1%, at one year 36.4%, and at four years 58.3%. The target lesion revascularisation (TLR) rate at six months was 12.9%, at one year 28.3%, and at four years 50.4%. From multivariate analysis, dose < 18 Gy was the most significant predictor of TLR. At four years the cumulative incidence of death was 3.8%, of myocardial infarction 13.4%, and of coronary artery bypass surgery 11.3%. Total vessel occlusion was documented in 12.3% of the patients. CONCLUSIONS: In the long term follow up of patients after IRT, there are increased adverse cardiac events beyond the first six months.

Drug-eluting stents: from randomized trials to the real world.

Drug-eluting stents have been developed to prevent in-stent restenosis following percutaneous coronary revascularization. In a number of randomized trials, polymer-coated sirolimus- and paclitaxel-eluting stents have been proven to markedly reduce the incidence of angiographic restenosis and repeat revascularization when compared to bare metal stents. Effectiveness of sirolimus-eluting stents in the prevention of restenosis has been confirmed in many subsets of patients and lesions not included in randomized trials, such as in-stent restenosis, chronic total occlusion, acute myocardial infarction, and others. Very promising data in the real world are emerging for utilization of paclitaxel-eluting stents as well. Other drug-eluting stents gave less brilliant results or even true failures, whilst a number of new drugs and stent platforms are under clinical or preclinical evaluation. In this review we describe the main clinical trials on drug-eluting stents, and the most recent informations derived from observational studies and registries. Moreover, preliminary results on new drug-eluting stents are summarized.

Beneficial effects of fluvastatin following percutaneous coronary intervention in patients with unstable and stable angina: results from the Lescol intervention prevention study (LIPS).

AIMS: To investigate the effect on risk of major adverse cardiac events (MACE) of lipid lowering treatment with fluvastatin 80 mg/day after a first percutaneous coronary intervention in patients with stable and unstable angina. METHOD AND RESULTS: This prespecified subgroup analysis of the LIPS (Lescol intervention prevention study) analysed 1658 patients with documented diagnosis; 824 had unstable angina (417 randomly assigned to fluvastatin, 407 to placebo) and 834 had stable angina (including silent ischaemia; fluvastatin, 418; placebo, 416). Median follow up was 3.9 years. There was no significant effect of anginal status on long term risk of MACE. Fluvastatin treatment reduced the risk of MACE by 28% compared with placebo (p = 0.03) among patients with unstable angina, with no difference between patients with stable and patients with unstable angina (relative risk 1.07, 95% confidence interval 0.87 to 1.30, p = 0.53). Fluvastatin reduced coronary atherosclerotic events (MACE excluding restenosis) by 36% (p = 0.006) among patients with unstable angina and 31% (p = 0.02) among patients with stable angina. Fluvastatin caused similar reductions in total cholesterol and low density lipoprotein cholesterol concentrations in both patient groups. CONCLUSION: Treatment with fluvastatin 80 mg/day produced significant reductions in MACE and coronary atherosclerotic events after percutaneous coronary intervention in patients with average cholesterol concentrations. The beneficial effects of fluvastatin are observed in patients with unstable or stable angina alike.

Routine sirolimus eluting stent implantation for unselected in-stent restenosis: insights from the rapamycin eluting stent evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry.

OBJECTIVE: To assess the effectiveness of routine sirolimus eluting stent (SES) implantation for unselected patients with in-stent restenosis and to provide preliminary information about the angiographic outcome for lesion subgroups and for different in-stent restenosis patterns. DESIGN: Prospective, single centre registry. SETTING: Tertiary referral centre. PATIENTS: 44 consecutive patients (53 lesions) without previous brachytherapy who were treated with SES for in-stent restenosis were evaluated. Routine angiographic follow up was obtained at six months and the incidence of major adverse cardiovascular events was evaluated. RESULTS: At baseline, 42% of the lesions were focal, 21% diffuse, 26% proliferative, and 11% total occlusions. Small vessel size (reference diameter < or = 2.5 mm) was present in 49%, long lesions (> 20 mm) in 30%, treatment of bypass grafts in 13%, and bifurcation stenting in 18%. At follow up, post-SES restenosis was observed in 14.6%. No restenosis was observed in focal lesions. For more complex lesions, restenosis rates ranged from 20-25%. At the one year follow up, the incidence of death was 0, myocardial infarction 4.7% (n = 2), and target lesion revascularisation 16.3% (n = 7). The target lesion was revascularised because of restenosis in 11.6% (n = 5). CONCLUSIONS: Routine SES implantation is highly effective for focal in-stent restenosis and appears to be a promising strategy for more complex patterns of restenosis.

Sirolimus-eluting stents for the treatment of in-stent restenosis.

The treatment of in-stent restenosis (ISR) remains one of the major therapeutic challenge for the interventional cardiologist. All percutaneous mechanical approaches have shown disappointing results and the recurrence of ISR was reported to be unacceptably high. Currently, the only proven effective therapy available for the treatment of ISR, at least for the most complex lesions, is vascular brachytherapy. However, this therapy is limited by potential side effects and logistic requirements. The introduction of drug-eluting stents, that carry and release antiproliferative agents, have demonstrated to virtually eliminate ISR in de novo lesions. In the light of this promising results for de novo lesions, sirolimus-eluting stents (SES) were recently used for the treatment of ISR in 2 pilot studies. In Sao Paulo, 25 patients with ISR treated with SES (1.4 stent per lesion) presented 4% ISR and no clinical events at 1 year. In Rotterdam, 16 patients with severe ISR were treated with 26 SES. Intravascular ultrasound evaluation demonstrated successful inhibition of neointimal hyperplasia with 1.1% volume obstruction of the stent, which is similar to the Sao Paulo series (0.8%). At 9 months clinical follow-up, 3 patients had experienced 4 major adverse cardiac events (2 deaths and 1 acute myocardial infarction necessitating repeat target vessel angioplasty). With the results presently available, SES implantation can be considered safe and potentially efficacious in the treatment of ISR. However, multicenter, long-term randomized studies are warranted in order to evaluate this new treatment concept.

Coronary artery bypass surgery and percutaneous transluminal coronary angioplasty in patients with multivessel disease.

Since its introduction in the early 1970s, coronary artery bypass grafting (CABG) surgery has been proven to relief anginal symptoms in patients with severe myocardial ischemia. Percutaneous coronary intervention (PCI) was introduced in clinical practice at the end of the 1970s and this treatment has also been established to be effective. PCI has now surpassed CABG as the most common means for treating coronary artery disease (CAD). However, restenosis remains its Achille's heel. Until the mid-1990s, a coronary reintervention was needed in 35% to 40% of the patients. Since then, interventional techniques and technology have evolved with improved success in more complex and anatomical settings, and restenosis has been now consistently decreased to around 20%. Despite all these improvements, the incidence of restenosis, especially in the 1(st) year, is still an important limitation to PCI. The major determinants of restenosis are elastic recoil, negative vessel remodeling and neointimal proliferation as a response to vessel injury induced by angioplasty devices. The use of conventional stents has provided an efficient method to face the first 2 problems, but neointimal proliferation is not affected by stenting. A new approach consists of using the stent as a drug carrier to the target site in order to inhibit restenosis. The first results of utilization of these fascinating drug-eluting stents (DES) to treat relatively simple lesions are very promising, but further analyses for more complex lesions such as those commonly found in daily practice are needed before any definitive conclusions can be made.

Ultrasound-assisted stent implantation in small size coronary arteries: a pilot study.

BACKGROUND: Many studies have indicated that a small lumen size is one of the most important predictors of acute events and of late restenosis after balloon angioplasty or stent implantation. In the last few years many studies have shown that intravascular ultrasound (IVUS) guidance makes it possible to optimize stent implantation. The aim of this pilot study was to evaluate the feasibility and safety of IVUS imaging of small vessels. Secondary endpoints were the immediate and long-term results of IVUS-guided elective BeStent implantation in small vessels. METHODS: Fourteen symptomatic patients with small coronary vessel (mean angiographic reference diameter 2.3 +/- 0.2 mm) disease underwent IVUS-guided BeStent implantation. IVUS success was defined as the achievement of a final minimal intrastent cross-sectional area (CSA) > 90% of the smaller reference lumen CSA. RESULTS: IVUS evaluation was feasible in all patients without any clinical or angiographic adverse events. Procedural success was achieved in all patients with implantation of a BeStent 15 mm. No major complication (death, myocardial infarction, stent acute or subacute thrombosis, coronary artery bypass, re-coronary angioplasty) occurred during the in-hospital phase. Two non-flow-limiting, asymptomatic coronary dissections were detected after stent expansion. The post-stenting lesion stenosis rate decreased from 72.9 +/- 12.9% to 0.75 +/- 11.7% with an acute gain of 1.8 +/- 0.4 mm. The final IVUS minimal stent CSA was 5.6 +/- 1.1 mm2. The IVUS criteria of adequate stent expansion were reached in 11 (78.6%) patients. At 6 months of follow-up, the rate of angiographically diagnosed in-stent restenosis was 30.7%; the 6-month late loss in stent diameter was 1.1 +/- 0.6 mm. No patient died or presented with a myocardial infarction. The target lesion revascularization rate was 30.7%. CONCLUSIONS: Coronary IVUS-guided stenting can be performed in small vessels with a high success rate and low incidence of in-hospital complications. However, despite these encouraging short-term results, the long-term clinical and angiographic outcome is less favorable. Further larger and randomized IVUS studies, probably employing more aggressive IVUS criteria, are needed to clarify the true role of IVUS guidance in this particular field.

Are there gender differences in patients presenting with unstable angina?

BACKGROUND: There are limited studies on gender differences in patients with unstable angina. We investigated the influence of gender in these patients in a tertiary referral centre. METHODS AND RESULTS: Three hundred and thirteen consecutive patients (210 men and 103 women) with unstable angina were studied over a 42-month period. Patient characteristics, cardiovascular risk factors and subsequent management including coronary artery bypass graft (CABG) operation and percutaneous transluminal coronary angioplasty (PTCA) were investigated. There was no difference in age [61.6 (11.0) (S.D.) years for men vs. 63.5 (10.5) years for women]. Diabetes mellitus and hypertension were more common in women (diabetes, 11% vs. 23%, P = 0.007; hypertension, 32% vs. 52%; P = 0.001). The number of smokers was greater in men (73% vs. 46%, P = 0.00001). There was no difference in the prevalence of hypercholesterolaemia or in the incidence of previous myocardial infarction, previous history of angina and family history of ischaemic heart disease. The duration of unstable angina before presentation to the referring hospital was similar in both sexes. The use of aspirin, intravenous heparin and antianginal drugs was also comparable in the two genders. The number of coronary arteries involved in men and women appeared similar (one vessel, 22% vs. 27%; two vessels, 26% vs. 21%; three vessels, 52% vs. 52% in men and women, respectively). The proportion of men and women who underwent subsequent revascularisation was also similar (CABG, 31% vs. 33%; PTCA, 42% vs. 40%). The overall in-hospital mortality was higher in women (6.8% vs. 2.8%), but was not statistically significant (P = 0.18). CONCLUSIONS: Gender differences in unstable angina manifest in the preponderance of selected risk factors including diabetes mellitus and hypertension in women and smoking in men. There is no difference in age, the degree of coronary artery involvement and the subsequent management in a tertiary referral centre.

Long-term follow-up of stent implantation versus stent-like angioplasty in unstable angina.

Stent-like plain old balloon angioplasty (POBA, < or = 30% residual diameter stenosis) in patients with stable angina resulted in a clinical and angiographic long-term outcome equivalent to stenting. In unstable angina POBA showed lower acute and long-term efficacy than in the stable setting. Data comparing stent-like POBA and coronary stenting in unstable angina are lacking in the literature. The aim of this retrospective single-center study was to compare the long-term effectiveness of stent-like POBA and coronary stenting in unstable angina. From January 1996 to December 1996 we retrospectively examined 187 consecutive patients with unstable angina who underwent coronary angioplasty on a native vessel: 135 had coronary stenting in addition to POBA and 50 achieved a stent-like result with POBA. Two patients, with major contraindication to coronary stenting, who did not reach a stent-like angiographic result, were also treated with only POBA but were excluded from the study. Stent implantation indications were: elective (54 stents, 30%), suboptimal angiographic result (104 stents, 58%), and bail-out situation (21 stents, 12%). Stent implantation showed high angiographic (98.5%) and clinical (95.5%) success. Stent thrombosis occurred only in 2 patients (1.5%). At quantitative coronary angiography the stent group showed a higher post-procedure minimal lumen diameter (2.74 +/- 1.25 vs 2.27 +/- 0.58 mm, p = 0.025), acute gain (1.95 +/- 1.28 vs 1.43 +/- 0.57 mm, p = 0.007) and lower residual stenosis diameter (13.89 +/- 7.43 vs 20.4 +/- 7.28%, p = 0.001) than the stent-like POBA group. At 1-year follow-up the stent group showed a higher event-free survival rate (77.9 vs 64.6%, p = 0.009) mainly due to lower recurrence of angina and repetition of percutaneous procedures. Stent-like POBA procedure and baseline lesion length > or = 10 mm proved to be the only independent predictors of long-term ischemic event occurrence. In conclusion, in unstable angina, stent implantation appears more effective than stent-like POBA to avoid long-term ischemic complications.

Coronary stenting for unstable angina: predictors of 30-day and long-term clinical outcome.

BACKGROUND: Unstable angina is usually caused by acute thrombosis superimposed on a fissured plaque. Coronary artery stenting has been shown to improve short- and long-term results of coronary angioplasty in mainly stable patients with one-vessel disease, but it is uncertain whether its use in an unstable clinical setting can be safe and useful. This study sought to evaluate the results of coronary stenting in unstable angina and to determine patient, lesion and procedure-related predictors of 30-day and long-term ischemic events. METHODS: We studied 266 consecutive patients (mean age 62 +/- 9 years) with unstable angina who underwent coronary artery stenting. The procedure was performed electively in 24%, in bailout situations in 11% and for a suboptimal result of conventional angioplasty in 65%. After stent implantation, patients were treated with anticoagulation (61) on combined antiplatelet therapy (200). Multivariate logistic regression analyses were performed to determine 30-day and long-term predictive factors of ischemic complications. RESULTS: Procedural success was obtained in 261 patients (98.1%). During the first 30 days after stenting, one patient died from cardiogenic shock (0.3%) and six (22%) suffered a non-fatal Q-wave myocardial infarction. Patients with combined antiplatelet therapy had a significantly lower stent thrombosis rate (1.5% versus 11.4%, P = 0.002) than those treated with anticoagulant regimen. At long-term follow-up (17.7 +/- 9.4 months) cardiac mortality myocardial infarction and target-vessel revascularization rates were 0.4%, 1.5% and 9.3%, respectively. In multivessel and diabetic patients, a worse long-term event-free survival was observed. Logistic multivariate analysis revealed bailout stenting, anticoagulant therapy, implantation of stents longer than 15 mm as predictors of 30-day ischemic events. In addition, multivessel coronary artery disease and stent application with balloon size of less than 3 mm were predictive of long-term ischemic events. CONCLUSIONS: This study demonstrates that, either electively or after failure of conventional angioplasty, coronary stenting represents an effective therapy for patients with unstable angina. In the same clinical setting, combined antiplatelet therapy is associated with a lower 30-day stent thrombosis rate than anticoagulant therapy. Bailout stenting, anticoagulant therapy, implantation of stents longer than 15 mm were shown to be predictors of 30-day ischemic events, whereas multivessel coronary artery disease and stent application with small balloon size were predictive of long-term ischemic events.

Long-term (5 year) effects of transient (silent) ischaemia on left ventricular systolic function in stable angina. Clinical and radionuclide study.

AIMS: (a) to assess short (1 year) and long-term (5 year) changes in left ventricular ejection fraction in patients with stable coronary disease with or without ECG evidence of transient ischaemia during daily life on routine therapy, and (b) to assess whether patients with recurrent transient ischaemic episodes have a particular propensity to gradual deterioration in left ventricular ejection fraction in the absence of infarction. METHODS AND RESULTS: One hundred and forty eight patients (127 males; mean age 59 years), part of a natural history cohort of 172 patients who had undergone exercise testing, 48 h ambulatory ST monitoring, and resting radionuclide ventriculography at baseline, and who had not suffered any intervening cardiac event, underwent repeat radionuclide ventriculography at 1 year follow-up on identical or very similar medications. Furthermore, 56 patients (50 males; mean age 65 years) of this cohort, who had ischaemia both on exercise testing and ambulatory monitoring at baseline (n=33), or no ischaemia on either test at baseline (n=23), and who had suffered no intervening event, underwent repeat exercise testing, ambulatory monitoring and radionuclide ventriculography at a mean of 61.8 months follow-up. In 38 of these 56 cases, long-term testing mirrored baseline testing in terms of presence or absence of ischaemia (both tests +, n=25; both tests -, n=13). At one year there was no change in left ventricular ejection fraction, either for the whole group (n=148; left ventricular ejection fraction 47=11.6% - 47.13+11.07%, P=ns) or for subgroups with (n=62; left ventricular ejection fraction 48+12.1%-48.5+10.5%, P=ns) and without (n=86; left ventricular ejection fraction 46.2+10.4%-46.2+11.3%, P=ns) evidence of transient ischaemia at baseline. At 61 months, there was a small fall in mean left ventricular ejection fraction for the total study group (n=56; left ventricular ejection fraction 45.8+9.3%-42.1+8.8%, P<0.05); however, this fall was not significant for those patients with both baseline and 5 year evidence of transient ischaemia (n=25; left ventricular ejection fraction 44.9+8.7%-41.3+7.5%, P=0.056). CONCLUSION: In medically treated stable coronary patients who do not suffer any intervening cardiac event, recurrent transient (silent) ischaemic episodes do not, in themselves, lead to gradual deterioration in left ventricular systolic function over a 1-5 year period.

The management of hypercholesterolaemia in patients with coronary artery disease referred for coronary angiography.

There are clear benefits in treating hypercholesterolaemia in patients with ischaemic heart disease, especially those with previous myocardial infarction. Following publication of trial evidence and treatment guidelines for hypercholesterolaemia, we investigated the current practice of the management of hypercholesterolaemia in patients with coronary artery disease referred for coronary angiography by general physicians. We prospectively reviewed 156 consecutive patients (117 men; mean age 61.5+/-9.6 [S.D.] years) with a history of angina pectoris who attended the day case unit for coronary angiography in a 10 week period. Nearly a tenth of these patients had not been screened for hypercholesterolaemia in this study. Of those patients with a cholesterol level > or =5.5 mmol/l, almost a quarter were not on a statin or any other cholesterol-lowering therapy. Continued effort should be given to the screening and effective management of hypercholesterolaemia in patients with coronary artery disease.

[Age-related changes in the renin-angiotensin-aldosterone system and the sympathetic nervous system in patients with essential hypertension]. / Modificazioni del sistema renina-angiotensina-aldosterone e dell'attività simpatica nei pazienti ipertesi essenziali, con il variare dell'età.

The aim of this study was to evaluate age, plasmatic renin activity (PRA), plasma aldosterone levels and the total quantity of urinary catecholamines (TOT. UR. CAT.) in a large population of out-patients suffering from essential arterial hypertension (EAH). A total of 986 patients were examined (540 women and 426 men aged between 15 and 87 years) suffering form slight or moderate EAH (WHO stage 1-2). After a wash-out period of two weeks, systolic and diastolic arterial pressure was measured together with heart rate in clino- and orthostatism. Blood samples were collected to determine PRA and plasma aldosterone, and lastly a 24-hour urine collection was made to measure the total quantity of catecholamines. It emerged that there was a significant increase in systolic pressure, whereas heart rate and PRA diminished significantly when correlated with age; diastolic pressure was also considerably lower, but did not reach statistical significance. Moreover, it was found that there was a significant positive correlation between PRA and TOT. UR. CAT., whereas no correlation was found between age and plasma aldosterone and between blood pressure and the various endocrine parameters examined. These data confirm the changes in the biological, hemodynamic and endocrine profiles observed in elderly hypertensive patients in comparison to young hypertensive patients, and suggests that age may be an important predictive factor of the activity of both the renin-angiotensin and sympathetic nervous system which appear to be closely connected and gradually attenuated by age.

[Role of aldosterone in essential arterial hypertension complicated by chronic renal insufficiency]. / Ruolo dell'aldosterone nell'ipertensione arteriosa essenziale complicata da insufficienza renale cronica.

The following parameters were studied in a group of patients suffering from essential arterial hypertension complicated by chronic renal insufficiency (CRI), mean age = 64.31 +/- 1.84, with creatinine clearance (CrC) ranging between 30 and 60 ml/min: blood pressure (systolic and diastolic arterial pressure), heart rate, plasmatic renin activity (PRA), plasma levels of aldosterone (ALDO) both in clino- and orthostatism, as well as some metabolic parameters. All parameters were compared with those in a group of age- and sex-matched patients with slight or moderate essential arterial hypertension. Before starting the study all patients completed a wash-out period of one week to annual the effects of other drugs which might interfere with the RAA system. PRA levels were within the norm, whereas plasma levels of ALDO were high both in clino- and orthostatism. ALDO levels were also found to be inversely correlated with those of CrC. From these data it emerges that hyperaldosteronism, as observed in these patients with CRI, is a relatively reliable marker of the extent of CRI and may occur independently of the activation of the RAA system, given that other factors, such as orthostatic stimulation, alterations in the acid-base equilibrium, and the degree of aldosterone hepatic and urinary clearance, contribute to its pathogenesis.

[Evaluation of the hereditary component in patients with essential arterial hypertension]. / Valutazione della componente ereditaria nei pazienti affetti da ipertensione arteriosa essenziale.

As is well known, genetic factors play a decisive role in the pathogenesis of essential hypertension (EH), even if they are closely related to environmental factors; it is therefore not possible to quantify with any degree of certainty the role and importance of each in the onset of hypertensive disease. The aim of the present study was to ascertain the presence of hypertensive 1st and 2nd degree ascendant, collaterals and descendants in a group of 355 out-patients with EH (167 males, 188 females; mean age: 52.9 +/- 0.7 years) using an anamnestic analysis. The results of this study confirmed the high prevalence of the hereditary component in EH: familial hypertension was found in 60.6% of the group. From a detailed analysis of the group, with regard to hypertensive ascendant, the hereditary transmission of EH by the mother was significantly higher than that by the father, both the parents and the forefathers, even if it is worth pointing out that the penetration of the genetic character was not always sex-related and was equally distributed between male and female descendents. In addition, it was observed that patients with a familial pattern of hypertension in common with collateral relatives showed significantly enhanced levels of systolic and diastolic pressure in relation to those with another hereditary component. These findings serve to underline the importance of evaluating the effective incidence of EH with regard to an entire family nucleus and not only in individual terms, in order to identify the various means of genetic transmission and possible interactions with environmental factors.