Blood pressure reactivity to mental stress task as a determinant of sustained hypertension after 5 years of follow-up.

Previous studies have reported an increased risk of developing sustained hypertension (SH) in borderline or mildly hypertensive subjects showing an exaggerated response of blood pressure (BP) to mental stress. The aim of this study was to assess if the response of BP to mental stress tasks is an independent predictor of SH. A total of 89 patients with grade 1 hypertension, aged 18-64 years, 62% males, were included. The mean of follow-up was 5.3 years (s.d. 2.1 years). SH was defined as the development of grades 2-3 hypertension (Systolic BP>or=160 mmHg or diastolic BP>or=100 mmHg) or to be in antihypertensive treatment after follow-up. Two mental stress tasks: mental arithmetic stress task and a stressful interview (SI) were applied at entry. The subjects were classified as hyper-reactors when BP increase was greater than 35 mmHg for systolic BP or greater than 21 mmHg for diastolic BP, according to the results obtained previously in a normotensive control group. In the univariate analysis, the factors associated with the development of SH were age (P=0.0007), office diastolic BP (P=0.014) and hyper-reactivity of BP during a stressful interview (P=0.003). In the Cox regression model, after adjusting for gender, age, and office BP, the hyper-reactivity of BP during SI was an independent predictor of development of SH. In conclusion, the response of BP to mental stress tasks is useful in predicting SH in young and middle-aged subjects with grade 1 hypertension.

Marked neointimal lipoprotein lipase increase in distinct models of proclivity to atherosclerosis: a feature independent of endothelial layer integrity.

Lipoprotein lipase (LPL) in the arterial wall has been proposed to enhance the retention of apoB-containing lipoproteins, an early event in atherosclerosis. As the neointima is considered the primary site of lipid accumulation in atherogenesis, the arterial expression and location of LPL was investigated in distinct experimental models of neointimal formation in normolipidemic rabbits and rats. Neointima elicited by balloon aortic denudation or raised beneath an anatomically intact endothelial layer by placing a silastic collar around the common carotid artery, both showed a striking LPL immunostaining that mostly co-localized with neointimal smooth muscle cells. Besides, increased LPL protein and mRNA in deendothelialized aortas was demonstrated by Western and Northern blot analysis, respectively, suggesting an enhanced expression of LPL in injured arteries. It was concluded that LPL is increased in neointima developed in either denuded vessels or arteries with a preserved endothelium, a finding which suggests that LPL abundance may be an attribute of the neointima, whatever the stimulus that promotes its formation. On the basis of former evidence concerning the role of LPL in lipid retention, this study provides a possible explanation for the injury-induced vessel susceptibility to atherosclerosis, and the particular proneness of the neointimal layer to lipid accretion.

Determinants of left ventricular mass in untreated mildly hypertensive subjects: hospitalet study in mild hypertension.

The objectives of this cross-sectional study were to identify the determinants of left ventricular mass in untreated mildly hypertensive subjects at the Hypertension Unit, Department of Internal Medicine, Red Cross Hospital, Hospitalet de Llobregat, Barcelona, Spain. One hundred seventy-one untreated mildly hypertensive subjects, with a mean age of 41.1+/-11.8 years (from 18 to 65 years) were sequentially visited in our Unit; 54% were men. Echocardiographic measurements of good quality were obtained in 142 subjects (83%). Two-dimensional guided M-mode echocardiograms were used and left ventricular mass was estimated according to the Penn convention. Left ventricular mass (LVM) was analyzed as a continuous variable. In the bivariate analysis, the variables that significantly correlated with LVM were patient's height (r = 0.42, P<.0005), weight (r = 0.47, P< or =.0005), heart rate (r = -0.22, P = .01), HDLc (r = -0.30, P = .002), hematocrit (r = -0.28, P = .001), urinary sodium excretion (r = 0.23, P = 0.012), and different measurements from the ambulatory blood pressure profile for 24 h. By means of multiple regression analysis, a maximum of 41.2% of LVM variability could be explained from the factors registered in our study. The final model included age, gender, patient's weight, and diastolic night load from ambulatory blood pressure monitoring. When added to different models, weight and diastolic night load showed a similar strength in predicting left ventricular mass. In untreated patients with mild hypertension, traditional factors such as blood pressure levels explain a maximum of 41.2% of LVM variability. More knowledge is needed about factors that may alter cardiac morphology in the evolution of hypertensive patients.

[Subclinical atherosclerosis. An objective index of susceptibility and vascular risk]. / Aterosclerosis subclínica. Un índice objetivo de susceptibilidad y riesgo vascular.

Clinical data suggest that the individual susceptibility to atherosclerosis is not accounted for only by exposure to classical or "emerging" vascular risk factors. Although recent investigations with transgenic animals have revealed new genetic determinants of susceptibility, little is known concerning this situation in human beings. Even though the human genome project might uncover specific genetic markers in the future, the only early and objective method to identify the susceptible individual at present is to detect atherosclerosis non-invasively. High resolution B-mode ultrasonography of superficial arteries coupled with advanced computer-assisted image processing systems is a highly reproducible method to perform a quali-quantitative early evaluation of already developed wall lesions. Clinically more significant, the detection of silent atherosclerosis has an additional value for risk factor assessment in the prediction of global vascular risk, a relevant index for decision-making in cardiovascular prevention. It is conceivable that the introduction of non-invasive measures of the atherosclerotic burden in risk stratification of asymptomatic subjects will help to target interventions for more rational risk factor control and to reduce the cost/benefit ratio of primary prevention.

Aterosclerosis subclínica. Un índice objetivo de susceptibilidad y riesgo vascular. / [Subclinical atherosclerosis. An objective index of susceptibility and vascular risk]

Clinical data suggest that the individual susceptibility to atherosclerosis is not accounted for only by exposure to classical or [quot ]emerging[quot ] vascular risk factors. Although recent investigations with transgenic animals have revealed new genetic determinants of susceptibility, little is known concerning this situation in human beings. Even though the human genome project might uncover specific genetic markers in the future, the only early and objective method to identify the susceptible individual at present is to detect atherosclerosis non-invasively. High resolution B-mode ultrasonography of superficial arteries coupled with advanced computer-assisted image processing systems is a highly reproducible method to perform a quali-quantitative early evaluation of already developed wall lesions. Clinically more significant, the detection of silent atherosclerosis has an additional value for risk factor assessment in the prediction of global vascular risk, a relevant index for decision-making in cardiovascular prevention. It is conceivable that the introduction of non-invasive measures of the atherosclerotic burden in risk stratification of asymptomatic subjects will help to target interventions for more rational risk factor control and to reduce the cost/benefit ratio of primary prevention.

[Effect of diltiazem on cold-induced left ventricular dysfunction in patients with systemic sclerosis]. / Efecto del diltiazem sobre las alteraciones cardíacas inducidas por el frío en la esclerosis sistémica.

Patients with systemic sclerosis (SS) have cardiac dysfunction induced by cold exposure. We and others have demonstrated this finding after corporal chilling, suggesting a "coronary Raynaud phenomenon" mediated by intermittent vascular spasm. In this study we evaluated the effect of diltiazem (DTZ) in cardiac dysfunction induced by cold test in patients with SS without clinical evidence of heart disease. Twelve patients with SS were studied. One patient was excluded because he did not fulfill the prescribed treatment. Eleven patients (age of 49.9 +/- 3.8 years and illness duration of 9.3 +/- 4.8 years) were included. Gated equilibrium radionuclide ventriculography was recorded after red blood cells were labeled in vivo using an intravenous injection of stannous pirophosphate followed by 20 mc of 99 Tc (gamma camera with electrocardiographic R wave gating was used). Left ventricular injection fraction (LVEF) was calculated using computer analysis and wall motion abnormalities by visual interpretation. Patients were cooled using a thermic blanket set at 5 degrees centigrade. They were evaluated before and after a period of cooling. After corporal chilling LVEF decreased more than 10% in all of them. DTZ 270 mg a day was administered to the same patients during 48 hs. Basal and cold LVEF were repeated in all patients. The results with and without DTZ were compared by Student's t Test. The basal LVEF with and without DTZ was not different (64.8 +/- 2.6 and 63.1 +/- 1.8). After corporal chilling LVEF decreased (64.8 +/- 2.6 to 54.8 +/- 2.5 p < 0.00001) and reversible abnormalities in wall motion were noticed in patients without DTZ. When they received DTZ neither difference in LVEF (63.1 +/- 1.8 to 62.1 +/- 2.4) nor wall motion abnormalities were observed. We compared the LVEF after chilling (62.1 +/- 2.4 and 54.8 +/- 2.5) and we found an important difference with the use of DTZ (p < 0.005). It can be concluded that in patients with SS and no overt heart disease, DTZ prevents the early cardiac dysfunction induced by cold test. Probably this drug blunts the coronary spasm induced by cold test in this group of patients.

Determination of bezafibrate, ciprofibrate and fenofibric acid in human plasma by high-performance liquid chromatography.

A selective high-performance liquid chromatographic method to assess either bezafibrate, ciprofibrate or fenofibric acid plasma levels is described. Drugs are extracted with diethyl ether, after acidification with HCL. An isocratic acetonitrile 0.02 M H3PO4 (55:45) mobile phase, a C18 microns) column and UV detection are used. The LOQ found was 0.25 microgram/ml for the three fibrates. Intra- and inter-assay accuracy ranges were 90-107% and 82-111%: 96-115% and 94-107%: 94-114% and 94-126% for bezafibrate, ciprofibrate and fenofibric acid, respectively. Intra- and inter-assay precision (C.V.% ranges) were 1.72-3.06% and 2.66-7.67%: 1.88-4.64% and 0.62-2.99%: 1.26-4.69% and 3.56-7.17% for the three fibrates studied. Its sensitivity, accuracy and precision make it a useful tool for monitoring plasma levels of these drugs in a clinical setting and for research purposes.

Injury produces early rise in lipoprotein lipase activity in rabbit aorta.

The mechanisms following intimal injury predisposing towards atherosclerotic changes have not been fully elucidated. We speculated that a local increase in the enzyme lipoprotein lipase (LPL) might explain a higher susceptibility of the damaged intima to lipid accretion, and so we investigated the effect of balloon endothelial denudation on LPL activity and cholesterol content (LPLa and Cholc, respectively), in aortas from normolipidemic male New Zealand white rabbits. Arteries were obtained from injured and control animals after 2, 6, 8 and 10 weeks to evaluate the shortest period after de-endothelialization necessary to detect LPLa changes. Injury resulted in a 4-fold LPLa rise (P < 0.01), as early as 2 weeks, and the enzymatic activity remained increased throughout the study period. A mild but significant 22% Cholc increase (P < 0.03) was found after 2 weeks of injury, even in this normolipidemic rabbit model. We conclude that physical damage to the intima markedly and soon increases LPLa. This finding might account for the higher lipid accumulation by injured vessels, providing additional support to the hypothesis of LPL as an atherogenic mediator.

[Repeatability of insulin sensitivity estimation using the Minimal Model and comparison with a modified short low-dose insulin tolerance test]. / Reproducibilidad de la cuantificación de la sensibilidad a la acción insulínica con el modelo mínimo y comparación con un test de tolerancia a bajas dosis de insulina.

Hyperinsulinemia and insulin-resistance are metabolic disturbances associated with obesity, essential hypertension, hypertriglyceridemia, glucose intolerance, overt non-insulin dependent diabetes mellitus, polymetabolic syndrome and atherosclerotic disease. The assessment of in vivo insulin sensitivity (SAI in vivo) changes achieved by life style modifications or drug interventions require a reproducible technique. To evaluate the day-to-day intra-individual repeatability of SAI-in vivo, we determined the variation in the SI index (calculated from the Minimal Model of Bergman modified by insulin or MMins) in 11 subjects with a wide range of insulin-resistance. SI (first study) varied from 0.82 to 8.48 x 10(-4) min-1/microU.mL (4.43 +/- 2.85 x 10(-4) min-1/microU.mL mean +/- SD) and highly correlated with SI (second study) (r = 0.89; p = 0.0002). The average interday coefficient of variation was 20.9 +/- 13.9% and was similar in subjects with low or high SI values. We also measured SAI in vivo by assessing the rate of serum glucose decline induced by human cristalline insulin 0.025 U/kg IV dose after a 12-14 hours fasting period (a modified Bonora's method or BBD) in 11 subjects. No subject presented biochemical or symptomatic hypoglycemia. SAI in vivo values determined by BBD varied from 21 a 234 mumol/ml/min (134 +/- 64.8 mumol/ml/min, mean +/- SD). We found a highly significant correlation between SI values obtained from MMins and SAI in vivo assessed by the BBD (r = 0.89, p = 0.0002). Our results suggest that the Mmins is a fairly reproducible procedure and that a BBD is an acceptable option to quantify SAI in vivo, mainly when a fast-execution practice is necessary or cost restrictions are required.

[Cold-induced cardiac abnormalities in systemic sclerosis]. / Alteraciones cardíacas inducidas por el frío en la esclerosis sistémica.

Cardiac abnormalities are frequent in patients with systemic sclerosis (SS). These abnormalities have been demonstrated in over 80% of patients with SS and there are some clues that suggest that an intermittent vascular spasm (i.e. coronary Raynaud's phenomenon) is one of the causes of myocardial dysfunction in this group of patients. The aim of this prospective study was to evaluate the ventricular performance and regional wall motion during exposure to cold in patients with SS and Raynaud's phenomenon without overt cardiac disease. Twenty-four patients and 10 normal volunteers underwent radionuclide ventriculograms (RV). In each subject the RV was done thrice: basal, 20 minutes after chilling with thermic blanket and post reheating. The left ventricular ejection fraction (LVEF) decreased during the cold test (p = 0.03) with reversible abnormalities in wall motion. Basal Right Ventricular Ejection Fraction (RVEF) was lower than that of normal subjects (p = 0.02) and decreased during the cold test (p = 0.04). Therefore, we were able to demonstrate an early cardiac dysfunction associated with impaired wall motion after corporal chilling. These findings suggest that coronary spasm in SS would be an early and frequent phenomenon that would precede the development of symptomatic cardiac disease in some patients with this illness.

Alteraciones cardíacas inducidas por el frío en la esclerosis sistémica. / [Cold-induced cardiac abnormalities in systemic sclerosis]

Cardiac abnormalities are frequent in patients with systemic sclerosis (SS). These abnormalities have been demonstrated in over 80

of patients with SS and there are some clues that suggest that an intermittent vascular spasm (i.e. coronary Raynauds phenomenon) is one of the causes of myocardial dysfunction in this group of patients. The aim of this prospective study was to evaluate the ventricular performance and regional wall motion during exposure to cold in patients with SS and Raynauds phenomenon without overt cardiac disease. Twenty-four patients and 10 normal volunteers underwent radionuclide ventriculograms (RV). In each subject the RV was done thrice: basal, 20 minutes after chilling with thermic blanket and post reheating. The left ventricular ejection fraction (LVEF) decreased during the cold test (p = 0.03) with reversible abnormalities in wall motion. Basal Right Ventricular Ejection Fraction (RVEF) was lower than that of normal subjects (p = 0.02) and decreased during the cold test (p = 0.04). Therefore, we were able to demonstrate an early cardiac dysfunction associated with impaired wall motion after corporal chilling. These findings suggest that coronary spasm in SS would be an early and frequent phenomenon that would precede the development of symptomatic cardiac disease in some patients with this illness.