Arturo Fernández-Cruz

Prevalencia, distribución y variabilidad geográfica de los principales factores de riesgo cardiovascular en España. Análisis agrupado de datos individuales de estudios epidemiológicos poblacionales: estudio ERICE

Introduccion y objetivos Estimar la prevalencia y la distribucion geografica de los principales factores de riesgo cardiovascular en la poblacion espanola. Investigar la existencia de diferencias geograficas. Metodos Agregacion de ocho estudios epidemiologicos transversales, realizados en Espana entre 1992 y 2001, que superaron criterios de calidad metodologica. Reanalisis conjunto de los datos individuales por grupos de edad (20-44, 45-64 y ≥ 65 anos), sexo y grandes areas geograficas. Poblacion de estudio: 19.729 sujetos. Estimacion de valores medios y prevalencias crudas y ajustadas. Resultados Por orden decreciente, los factores de riesgo cardiovascular mas frecuentes en la poblacion espanola fueron la hipercolesterolemia (colesterol total > 200 mg/dl, 46,7%), hipertension arterial (37,6%), tabaquismo (32,2%), obesidad (22,8%) y diabetes mellitus (6,2%). Los valores medios de presion arterial, indice de masa corporal, colesterol de las lipoproteinas de alta densidad y glucemia varian ampliamente con la edad, el sexo y las areas geograficas. La mayor carga de factores de riesgo cardiovascular se observa en las zonas sureste y mediterranea y la menor, en las areas norte y centro. Conclusiones En Espana la prevalencia de los principales factores de riesgo cardiovascular es elevada. Hay marcadas diferencias geograficas en su distribucion.

Management of resistant arterial hypertension: role of spironolactone versus double blockade of the renin-angiotensin-aldosterone system

Background Currently there is no consensus regarding which add-on therapy to use in resistant hypertension. This study was designed to compare two treatment options, spironolactone (SPR) versus dual blockade of the renin–angiotensin–aldosterone system (RAAS). Methods Forty-two patients with true resistant hypertension were included in the study. An open-label prospective crossover design was used to add a second RAAS blocker to previous treatment and then SPR following 1 month of wash-out. BP was measured in the office and by ambulatory blood pressure monitoring (ABPM). Changes in laboratory tests were also studied for both treatments. The predictive values of aldosterone–renin ratio (ARR) and serum potassium of determining the antihypertensive response were analyzed for both arms. Results Following the first stage of dual blockade, SBP dropped significantly both in office (reduction of 12.9 ± 19.2 mmHg)) and by ABPM (reduction of 7.1 ± 13.4 mmHg). Office DBP was unchanged but was significantly reduced as measured by ABPM (3.4 ± 6.2 mmHg). On SPR treatment, office BP was reduced 32.2 ± 20.6/10.9 ± 11.6 mmHg. By ABPM the reduction was 20.8 ± 14.6/8.8 ± 7.3 mmHg (P < 0.001). The BP control was achieved by 25.6% of patients in dual blockade and 53.8% in SPR with office blood pressure. By ABPM, 20.5% were controlled on dual blockade and up to 56.4% with SPR. Serum potassium was a weak inverse predictor of the blood pressure-lowering effect of SPR. Conclusion SPR has a greater antihypertensive effect than dual blockade of the RAAS in resistant hypertension. SPR at daily doses of 25–50 mg shows a potent antihypertensive effect when added to prior regimes of single RAAS axis blockade in patients with resistant arterial hypertension.

Localisation of endothelin-1 mRNA expression and immunoreactivity in the retina and optic nerve from human and porcine eye. Evidence for endothelin-1 expression in astrocytes.

We have investigated the localisation of endothelin-1 (ET-1) mRNA and ET-1-like immunoreactivity in retina and anterior portion of optic nerve from human and porcine eyes. In situ hybridisation method revealed expression of ET-1 mRNA mainly in the innermost layers of the retinas, in the retinal pigment epithelium cells as well as in the astrocytes of the optic nerve. Immunohistochemical studies showed that ET-1-like immunoreactivity appeared in the same regions where ET-1 mRNA was expressed as well as in the inner nuclear layer and in the inner segments of photoreceptors. In the nerve fibre and ganglion cell layers, astrocytes expressed both glial fibrillary acidic protein and ET-1 proteins suggesting that these cells may secrete ET-1. Expression of ETA and ETB receptors in human retina were demonstrated by reverse transcription-polymerase chain reaction. Our results demonstrated expression of ET-1 in glial, neural and vascular components of retina and optic nerve from human and porcine eyes.

Circulating monocytes in patients with diabetes mellitus, arterial disease, and increased CD14 expression.

Low serum concentrations of high-density lipoprotein (HDL) cholesterol and elevated levels of acute-phase reactans are frequently found in patients with non-insulin-dependent diabetes mellitus (NIDDM) and cardiovascular disease. Changes in the phenotype of circulating monocytes have been reported with both of these circumstances in nondiabetic subjects. In the present study, we explored the possibility that similar changes may occur in circulating monocytes of patients with NIDDM and arterial disease. Two groups of subjects with NIDDM were studied: patients with cardiovascular disease (n = 25) were compared with a group without cardiovascular disease (n = 26); both groups were age- and sex-matched, had the same length of diabetes duration, and degree of glycemic control. Healthy nondiabetic volunteers of comparable age and sex (n = 35) formed the control group. There was no significant difference in the numbers of the CD14+/CD16+ monocyte subpopulations between the 3 groups. However, a significant graded increase of the mCD14 intensity expression values was observed among the groups, with the highest levels in patients with NIDDM patients and the lowest in nondiabetic subjects. The serum C-reactive protein concentrations were significantly higher in the group with arterial disease compared with those without arterial disease or healthy controls. In the group of patients as a whole, relative mCD14 intensity expression was significantly correlated with HDL cholesterol levels (inversely) and with serum concentrations of C-reactive protein. Serum HDL cholesterol levels and the C-reactive protein concentrations were also significantly correlated. We concluded that the increased mCD14 intensity expression on circulating monocytes may be an important contributor to the increased inflammatory response observed in patients with NIDDM and arterial disease, and eventually, to atherogenesis.

Local Non-Esterified Fatty Acids Correlate With Inflammation in Atheroma Plaques of Patients With Type 2 Diabetes

OBJECTIVE Atherosclerosis is prevalent in diabetic patients, but there is little information on the localization of nonesterified fatty acids (NEFAs) within the plaque and their relationship with inflammation. We sought to characterize the NEFA composition and location in human diabetic atheroma plaques by metabolomic analysis and imaging and to address their relationship with inflammation activity. RESEARCH DESIGN AND METHODS Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for metabolomic analysis imaging of frozen carotid atheroma plaques. Carotid endarterectomy specimens were used for conventional immunohistochemistry, laser-capture microdissection quantitative PCR, and in situ Southwestern hybridization. Biological actions of linoleic acid were studied in cultured vascular smooth muscle cells (VSMCs). RESULTS TOF-SIMS imaging evidenced a significant increase in the quantity of several NEFA in diabetic versus nondiabetic atheroma plaques. Higher levels of NEFA were also found in diabetic sera. The presence of LPL mRNA in NEFA-rich areas of the atheroma plaque, as well as the lack of correlation between serum and plaque NEFA, suggests a local origin for plaque NEFA. The pattern of distribution of plaque NEFA is similar to that of MCP-1, LPL, and activated NF-κB. Diabetic endarterectomy specimens showed higher numbers of infiltrating macrophages and T-lymphocytes—a finding that associated with higher NEFA levels. Finally, linoleic acid activates NF-κB and upregulates NF-κB–mediated LPL and MCP-1 expression in cultured VSMC. DISCUSSION There is an increased presence of NEFA in diabetic plaque neointima. NEFA levels are higher in diabetic atheroma plaques than in nondiabetic subjects. We hypothesize that NEFA may be produced locally and contribute to local inflammation.

High prevalence of secondary hypertension and insulin resistance in patients with refractory hypertension.

Objective: To determine causes of treatment resistance in patients with refractory hypertension, and to estimate the prevalence of true resistant hypertension. Methods: We studied 50 consecutive patients referred with refractory hypertension after exclusion of hypokalemia and stenosis of the renal artery. Ambulatory blood pressure monitoring was performed in all patients to detect white-coat effect. The patients were hospitalized, antihypertensive drugs were withdrawn and a screening for secondary hypertension was performed. In addition, these patients, and a control group of essential hypertensives controlled with three antihypertensive drugs, underwent a OGTT with 75 g of glucose. Results: Primary normokaliemic hyperaldosteronism was diagnosed in seven patients. Two patients had a pheochromocytoma and six had white-coat effect. The 35 remaining patients with true resistant hypertension shown significant differences in serum insulin and HOMA IR when compared with the control group. Conclusions: These findings show that among normokaliemic treatment-resistant hypertension, the presence of hyperaldosteronism and pheochromocitoma is quite high. Moreover, treatment resistance in hypertensive patients appears to be associated with insulin resistance.

Type B and type C natriuretic peptide receptors modulate intraocular pressure in the rabbit eye

We investigated (1) the in vivo functional significance of the type B (ANP(B)) and type C (ANP(C)) natriuretic peptide receptors in the rabbit eye by evaluating the effect of intracameral administration of C-type natriuretic peptide (CNP) and C-ANP-(4-23) on intraocular pressure, and (2) the action of CNP on guanylate cyclase activity in the rabbit ciliary process membranes. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were also studied for comparison. We demonstrated that the natriuretic peptides decrease intraocular pressure and stimulate guanylate cyclase activity, CNP being the most potent. The duration of the effect of C-ANP-(4-23) on intraocular pressure reduction was almost 9-fold that of the BNP and 20-fold that of ANP and CNP effect. This ligand increased threefold the immunoreactive natriuretic peptides levels in aqueous humour. Our data demonstrate the presence of functional ANP(A) and ANP(B) receptors in the rabbit eye and that the ANP(C) receptor modulates the concentration of the natriuretic peptides in the aqueous humour.

A prospective study of the management of non-massive pulmonary embolism in the home.

BACKGROUND The objective of this study is to compare the characteristics, outcomes, and clinical complications of patients with pulmonary embolism (PE) who were treated at home as outpatients versus traditional hospitalization. METHODS Prospective study from January 2006 to June 2007. Selected patients diagnosed at the Emergency Department with stable non-massive pulmonary embolism that met standard inclusion criteria of Hospital at Home (HH) were treated at home. Patients that did not meet these criteria were admitted to Conventional Hospitalization (CH). Major and minor bleeding, re-thrombosis, clinical course, unexpected returns to hospital, and need for hospital re-admission in the following 3 months were recorded. RESULTS 61 patients with PE were included (30 HH and 31 CH). Mean age 66.8 and 66.7 years in HH and CH, respectively. A history of neoplasm was found to be present in 13.3% and 9.7% of HH and CH patients. In the CH group, 19.3% of patients had prior thromboembolic disease. Concomitant DVT was seen in 40% and 29% of HH and CH patient. Pulmonary embolism was bilateral in 30% and 38.7% of HH and CH patients. No major bleeding, re-thrombosis, or death occurred. The home treatment was successfully completed in 100% of the patients. Three patients in the CH group had hospital-acquired infections. CONCLUSIONS Patients with stable non-massive pulmonary embolism may be safely treated under conditions of home hospitalization.

Rosuvastatin added to standard heart failure therapy improves cardiac remodelling in heart failure rats with preserved ejection fraction

Although statins may provide potential therapeutic pathways for patients with heart failure with preserved ejection fraction (HFpEF), no studies have evaluated statins in combination with standard HF therapy, which would reflect clinical practice more closely. To address this question, we evaluated whether rosuvastatin added to a standard HF therapy provides additional improvement in cardiac structure and function in rats with hypertensive heart failure (SHHF).

Lack of a direct regulatory effect of atrial natriuretic factor on prostaglandins and renin release by isolated rat glomeruli

We have tested the direct regulatory effect of synthetic Atrial Natriuretic Peptide (ANP, 8-33aa) on prostaglandins and renin release by isolated rat glomeruli. Variable incubation times and doses of ANP did not modify the rate of PGE2, PGF2a and TXB2 production. Similar results were obtained for renin release. These data do not support a role for ANP in the regulation of prostaglandins and renin release by rat glomeruli.