Fabry disease with early-onset ventricular dilation: A case report.

RATIONALE: The most common cardiac involvement of Fabry disease (FD) is left ventricular hypertrophy (LVH), which usually occurs in male patients over the age of 30. In rare cases, it can progress to ventricular dilation in the late stage of the disease. PATIENT CONCERNS: A 16-year-old boy presenting with recurrent extremity pain and chest distress was admitted to our hospital. Imaging examinations revealed ventricular dilation. DIAGNOSIS: α-Galactosidase A enzyme assay and GLA gene sequencing confirmed the diagnosis of FD and revealed a novel mutation c.76_77insT. INTERVENTIONS: The patient was treated using metoprolol (23.75 mg qd) and angiotensin-converting enzyme inhibitor (fosinopril sodium 5 mg qd). He refused enzyme replacement therapy for financial reasons. OUTCOMES: The echocardiography, electrocardiography, renal function, and routine blood and urine tests performed 20 months after the patients discharge from hospital showed no significant changes. The patient reported a slow and gradual decrease in the frequency and degree of pain and chest distress, starting approximately 24 months after discharge. LESSONS: Cardiac involvement of FD can progress rapidly in some cases. Screening for FD should be considered in patients with unexplained ventricular dilation, especially in those with a history of typical FD manifestations.

Cost-effectiveness of screening for albuminuria with subsequent fosinopril treatment to prevent cardiovascular events: A pharmacoeconomic analysis linked to the prevention of renal and vascular endstage disease (PREVEND) study and the prevention of renal and vascular endstage disease intervention trial (PREVEND IT).

OBJECTIVE: This study estimated the cost-effectiveness,from the Dutch health care perspective, of screening for albuminuria in the general Dutch population to prevent cardiovascular events (CVEs) with subsequent angiotensin-converting enzyme inhibitor treatment, using data from the Prevention of REnal and Vascular ENdstage Disease Intervention Trial (PREVEND IT). METHODS: PREVEND IT was a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design within the larger observational Prevention of REnal and Vascular ENdstage Disease (PREVEND) study. The PREVEND IT study was conducted to assess the effects of fosinopril 20 mg and pravastatin 40 mg on CVEs in subjects with specific inclusion criteria: urinary albumin excretion (UAE) rate in the range from 15 to 300 mg/d, blood pressure <160/100 mm Hg, and plasma cholesterol level <8.0 mmol/L. Cost-effectiveness estimates for the Dutch population were expressed in euros (2002; 1 euro = US 1.01 dollars) as net costs per life-year gained (LYG) in the baseline and sensitivity (stochastic) analyses. RESULTS: Data were assessed for 864 subjects, with a mean (SD) follow-up of 46 (7) months. CVEs occurred in 45 (5.2%) subjects. Subjects who received fosinopril had a 40% lower incidence of CVEs than subjects in the placebo group (3.9% vs 6.5%, respectively; P = NS). The cost-effectiveness of screening for albumnuria was determined to be euro 16,700/LYG for the study population. Stochastic analysis indicated that the probability of the cost-effectiveness being below the suggested Dutch threshold of euro 20,000/LYG was 59% in the baseline analysis. The probability of cost-effectiveness below euro 20,000/LYG would increase to 91% if only subjects with UAE >50 mg/d were treated with fosinopril. Limiting the screening to subjects aged >50 years and >60 years also improved cost-effectiveness. CONCLUSIONS: The results of our study suggest that screening the general Dutch population for albuminuria and subsequently treating those found positive with fosinopril may be cost-effective compared with no screening and adopting the Dutch health care perspective. However, confirmation from larger multicenter trials is needed.

Using ACE inhibitors appropriately.

When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are, in part, attributable to the renin-angiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction. altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include decreases in myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications. (Am Fam Physician 2002;66:473.)

[The estimation of cardiovascular risk in hypertensive patients is not modified by management of the hypertension]. / L'estimation du risque cardiovasculaire chez des patients hypertendus ne modifie pas la prise en charge de l'HTA.

OBJECTIVES: To compare antihypertensive therapeutic strategies and efficacy whether the physicians were aware or not of the calculated cardiovascular risk at 10 years obtained from the Framingham equation. It was also possible to evaluate the concordance of the general physicians estimation of the cardiovascular risk with the calculated percentage. METHODS: The participation of 953 general physicians to the study allowed to achieve an estimation of the absolute cardiovascular risk for 1,243 hypertensives. Patients were randomised in 2 groups according to the knowledge or not by the physicians of the calculated risk. The therapeutic strategy included a monotherapy (Fosinopril 20 mg/days) for a follow up of 8 weeks, with the possibility to increase the treatment after 4 weeks (Fosinopril + hydrochlorotiazide). To be included, patients had to be more than 18 and less than 75 years, and a blood pressure above 140/90 mmHg. Estimated and calculated cardiovascular risk at 10 years, were classified according to the 1999 WHO-ISH guidelines: low risk < 15%, medium risk 15-20%, high risk 20-30%, very high risk > 30%. RESULTS: In this population, aged 60 +/- 10 years, with 54% of men, the concordance between estimated risk and calculated risk was of 35%. This concordance was better for the "low risk" and "very high risk", but remains inferior to 50%. The determinants of concordance were: gender (male), smoking and a low HDL cholesterol. After 8 weeks of treatment, no difference was observed between the 2 groups concerning final blood pressure level, percentage of normalised patients and number of patients with bi-therapy. CONCLUSIONS: General physicians estimation of cardiovascular risk at 10 years of hypertensive subjects has a bad concordance with the calculated risk according to Framingham equation. The results of this study indicate that the estimation of cardiovascular risk of hypertensive subjects does not modify the management of hypertension.

Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.

Pharmacoeconomics of angiotensin converting enzyme inhibitors in heart failure.

As a result of the increasing cost of health care and the limited resources available, it has become more difficult to allocate resources efficiently and effectively in the health care system. This environment has led to the development of pharmacoeconomic studies, which have been designed in response to the need for assessment of the economic benefits of a product prior to its acceptance in the market. The field of pharmacoeconomics has grown rapidly, especially in relation to the development of new pharmacological products. Economic analysis is now routinely incorporated into many clinical trials, and this type of information, in conjunction with the usual safety and efficacy data, is becoming more important to pharmaceutical companies, regulatory authorities, third party payers, and end-users. The cost-effectiveness of angiotensin converting enzyme (ACE) inhibitors for the treatment of heart failure has been evaluated on the basis of a number of large-scale studies, including the Survival and Ventricular Enlargement (SAVE) study and the Veterans Administration Cooperative Vasodilator Heart Failure Trials (V-HeFT I and II). The cost-effectiveness of the ACE inhibitor captopril compares favorably with other cardiac interventions, reducing both mortality and the incidence of congestive heart failure (CHF). Captopril also appears to be cost-effective in the treatment of patients with left ventricular dysfunction after acute myocardial infarction. In addition, analysis of more recent studies of the treatment of fosinopril in patients with mild to moderate CHF have been performed and have proved this newer ACE inhibitor to be cost-saving in these patients.