Teodoro Marotta

Effects of alpha-adrenergic and beta-adrenergic receptor blockade on lipid metabolism

The role of lipoprotein lipase in the pathophysiology of lipid changes during alpha-receptor or beta-receptor blockade was evaluated in this clinical trial. Thirty hypertensive patients were given 2 mg of prazosin twice daily or 100 mg of metoprolol twice daily for 10 weeks, according to an open, randomized protocol. Both drugs were effective in reducing arterial blood pressure (from 153 +/- 16/102 +/- 6 mm Hg to 146 +/- 12/92 +/- 8 mm Hg with prazosin and from 158 +/- 17/103 +/- 8 to 144 +/- 14/94 +/- 10 mm Hg with metoprolol). Prazosin significantly reduced total plasma cholesterol from 202 +/- 39 to 188 +/- 36 mg/dl and increased high-density lipoprotein cholesterol from 36 +/- 8 to 40.5 +/- 11 mg/dl. Prazosin did not affect plasma triglycerides levels, whereas patients taking metoprolol had a slight rise in these levels, from 122 +/- 42 to 142 +/- 57 mg/dl, along with a decrease in high-density lipoprotein cholesterol from 37 +/- 10 to 31 +/- 8 mg/dl. The concentration of apoprotein B did not change significantly with either treatment. Lipoprotein lipase activity increased in the prazosin group from 28.4 +/- 16 to 37.7 +/- 14 mumol/liter per minute (p less than 0.01), but did not change significantly (29.9 +/- 12 versus 32.8 +/- 8 mumol/liter per minute) in patients treated with the beta blocker. These data, which confirm previous reports of serum lipid changes during antihypertensive therapy, suggest that alpha1 blockers may interfere with lipoprotein lipase, possibly by reducing its catecholamine-mediated inactivation.

Early changes of the arterial carotid wall in uncomplicated primary hypertensive patients. Study by ultrasound high-resolution B-mode imaging.

Arterial hypertension is frequently responsible for arteriosclerotic damage in the carotid region. Nevertheless, there is as yet no general agreement that hypertension is correlated with lesions detected by noninvasive means in the carotid arteries. We studied, by noninvasive echotomographic technique, 70 uncomplicated primary hypertensive individuals without clinically evident end-organ complications and 30 normotensive matched control subjects to detect early lesions of carotid arteries. The presence of other cardiovascular risk factors was assessed, and heart structure and function were studied by echocardiography. Although hypertensive individuals were comparable to control subjects for other risk factors, they showed a marked increase in the thickness of the intimal-medial complex of the carotid wall (0.71 +/- 0.4 versus 0.56 +/- 0.2 mm, P < .001 in the right carotid and 0.83 +/- 0.3 versus 0.58 +/- 0.2, P < .003 in the left), in left ventricular mass (203 +/- 52 versus 176 +/- 37 g, P < .05), and in the prevalence of definite plaques of the carotid wall, both monolaterally and bilaterally (P < .003 by chi 2 test). Among the different factors contributing to the increase in thickness of the carotid artery wall, standing blood pressure, serum triglycerides, and age were found to be the best predictors (they accounted for about 16% of the variability, P < .005). These results indicate that carotid arteries of hypertensive individuals undergo degenerative changes, just as shown for hypercholesterolemic and diabetic patients in other studies. This supports the use of B-mode ultrasound imaging to detect early involvement of the carotid region before the appearance of any end-organ damage of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Diameter and Blood Flow Velocities in Cerebral Circulation in Hypertensive Patients

BACKGROUND AND PURPOSE The recent development of noninvasive techniques for the evaluation of the carotid arteries has focused attention on the study of arterial wall thickness to identify early lesions of vessels in patients at high risk for atherosclerosis, such as those with hypercholesterolemia, diabetes mellitus, and hypertension. METHODS In a sample of 70 hypertensive patients without clinical evidence of target organ damage, we showed a thickening of the intimal plus medial layers compared with age- and sex-matched normotensive control subjects. In this sample we also studied the diameter of the carotid arteries by ultrasound imaging, and we studied flow velocities in common carotid, internal carotid, and middle cerebral arteries by Doppler technique. Pulsatility and resistance indexes were calculated. RESULTS Absolute values of the carotid diameter were similar in the two groups (6.3 +/- 0.7 versus 6.0 +/- 0.8 mm); however, the ratio of diameter to blood pressure was significantly reduced in hypertensive compared with normotensive subjects (5.3 +/- 0.7 versus 6.5 +/- 0.8; P < .001 for mean blood pressure). Parietal stress was increased in the hypertensive subgroup and significantly correlated with arterial diameter in the normotensive group but not in the hypertensive group. No significant differences between the two groups were observed in blood flow velocities, with the exception of a slight significant increase of mean velocity in the internal carotid artery in hypertensive patients (37.5 +/- 9.1 versus 32.7 +/- 3.0 cm/s; P < .02). CONCLUSIONS These results indicate that in addition to the degenerative changes of the common carotid wall, the diameter of the carotid artery and the relation to parietal stress show an early impairment in patients with uncomplicated hypertension.

Triglyceride-to-HDL-cholesterol Ratio and Metabolic Syndrome as Contributors to Cardiovascular Risk in Overweight Patients

Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high‐density lipoprotein cholesterol ratio (TG/HDL) ≥3.0 (in mg/dl) is a marker of insulin resistance in overweight persons. We aimed at assessing cardiovascular risk profile in 301 overweight elderly Neapolitan outpatients, according to TG/HDL ratio and metabolic syndrome (MS), diagnosed by National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. TG/HDL ratio was ≥3.0 in 97 patients (group A) and <3.0 in 204 (group B). Overall, 93–97% of group A patients and 38–51% of group B patients had MS, depending on the diagnostic criterion. Group A patients with MS had significantly higher waist‐to‐hip ratio, total and non‐HDL cholesterol than group B patients with MS. In group B, MS and non‐MS patients had similar waist‐to‐hip ratio, blood pressure, total and non‐HDL cholesterol. Ten year coronary risk, calculated by the Framingham equations (n = 243), was 10.3 ± 5% in group B, non‐MS patients; 13.1 ± 6% in group B, MS patients; 19.9 ± 8% in group A (F = 32.8; P < 0.001). At the multiple regression analysis, TG/HDL ratio was associated with coronary risk (r2 = 0.227) more closely than gender, blood pressure, waist‐to‐hip ratio, non HDL cholesterol, and MS considered as a whole. A separate regression analysis showed that the logarithmically transformed TG/HDL ratio, an index of the HDL cholesterol esterification rate, is also associated with coronary risk (r2 = 0.252). Thus, TG/HDL ratio could help to characterize high‐risk overweight patients deserving a special therapeutic effort. Cardiovascular risk profile of insulin‐sensitive patients, identified by lower values of this parameter, is only moderately affected by MS.

Doxazosin and captopril in mildly hypercholesterolemic hypertensive patients. The Doxazosin-Captopril in Hypercholesterolemic Hypertensives Study.

The evidence linking hypertension and hypercholesterolemia is strong and has fueled research into possible adverse effects of some antihypertensive agents on serum lipid profile. This multicenter, open, parallel study compares the effects of doxazosin and captopril on blood pressure, serum lipid levels, and quality of life in 224 hypercholesterolemic hypertensive patients. Blood pressure was significantly reduced in both treatment groups (p < 0.001) and was normalized (standing diastolic pressure < or = 90 mm Hg) in 73% of the doxazosin patients and 67% of the captopril group. Serum total cholesterol level was favorably reduced by both doxazosin (from 238 to 223 mg/dl, p < 0.001) and captopril (from 245 to 233 mg/dl, p < 0.001), whereas high density lipoprotein cholesterol concentration increased only in the doxazosin group (from 33 to 36 mg/dl, p < 0.001). The calculated 10-year risk for the development of coronary heart disease was reduced significantly (p < 0.001) by 28% in the doxazosin group and by 19% in the captopril group. The quality of life evaluation showed beneficial changes in both treatment groups. As a result of proven antihypertensive efficacy and a lack of unfavorable effects on lipid parameters and health status measures, these findings support the use of both doxazosin and captopril as agents of first choice in the treatment of hypertensive patients with associated lipid abnormalities.

Is the sympathetic nervous system altered in children with familial history of arterial hypertension

The sympathetic nervous system has been investigated in 42 children with family history of arterial hypertension and 68 children of the same age without hypertensive relatives. Pressure responses to mental arithmetic and to isometric handgrip stress were measured in both groups, along with 24 h catecholamine excretion. Resting blood pressure and heart rate did not show any difference between groups. The increase in diastolic pressure during the mental arithmetic exercise was, however, significantly greater in children with family history of hypertension. A sharp increase in blood pressure and heart rate was observed during isometric handgrip in both groups without any significant difference. Twenty-four hour catecholamine urinary excretion was significantly higher in the group with family history of hypertension (31 +/- 15 vs. 23 +/- 13 micrograms/24 h; p less than 0.05). These results seem to indicate that an initial impairment of the sympathetic activity is already detectable in young offspring of hypertensive patients.

Clinic-daytime blood pressure difference and cardiovascular damage.

OBJECTIVE To investigate whether the clinic-daytime blood pressure difference can provide information on vascular reactivity to stress comparable to that of simple noninvasive stimuli such as a cold pressor test and isometric exercise, and whether there is any relationship between this blood pressure difference and noninvasive measurements of the left ventricular mass and carotid arterial wall. DESIGN Patients with newly discovered, never-treated, sustained hypertension were included in the study after a 1 month run-in, during which time their blood pressure was measured three times at 2 week intervals. METHODS Blood pressure was measured by a noninvasive procedure at rest and during a cold pressor test and an isometric exercise. The difference was calculated for systolic, diastolic and mean blood pressure as resting minus daytime ambulatory blood pressure. Parameters of the posterior wall and septal thickness of the left ventricle, aortic root and left atrium were studied by M-mode echocardiography. Carotid wall thickness and diameter were measured using ultrasound. RESULTS The 90 patients enrolled in the study were divided into tertiles of clinic-daytime blood pressure difference. The composition of the groups differed in sex, since the majority of women were in the highest tertile, but was comparable for age, body mass index, renin-aldosterone axis and lipid and carbohydrate metabolism. Blood pressure responses to cold and isometric exercise were more pronounced in patients in the lowest tertile of blood pressure difference. No intergroup differences were detected in echocardiographic parameters of ventricular (left ventricular mass, tertiles I-III: 46.5 +/- 10, 42.3 +/- 8, 44.8 +/- 13 g/m2.7, respectively) and carotid (intima-media thickness, tertiles I-III 0.58 +/- 0.1, 0.54 +/- 0.1, 0.62 +/- 0.1 mm, respectively) structure. CONCLUSIONS The present study indicates that the clinic-daytime blood pressure difference provides different information on cardiovascular reactivity compared with that obtained from the cold pressor test and isometric exercise. Moreover, it does not seem to have any relationship with ventricular hypertrophy and/or carotid wall thickening.

Factors affecting lipoprotein lipase in hypertensive patients

Arterial hypertension is frequently associated with serum lipid abnormalities. Lipid metabolism can also be affected by antihypertensive treatment, possibly via an interference with lipoprotein lipase (LPL) activity. The aims of this study were to investigate the metabolic and hemodynamic factors that can interfere with plasma postheparin LPL activity in a sample of 13 patients with mild, uncomplicated arterial hypertension. The effects of vasodilator administration (prazosin and hydralazine) alone or in combination with a beta-blocker (propranolol) were also studied. A direct correlation between serum insulin levels and LPL activity was found during placebo treatment. This was confirmed by multiple regression analysis, which also showed a positive correlation of LPL activity with aortic flow velocity and plasma adrenaline (F significance = 0.0007, R2 = .905). Serum insulin was also directly correlated with cholesterol in high-density lipoproteins (HDLs) and in the HDL2 subfraction. A significant decrease in LPL activity was observed during the addition of propranolol to vasodilators as compared with vasodilators alone. A positive correlation was found between LPL and adrenaline changes induced by the combined treatment. These data suggest that LPL may play a role in the pathophysiologic connections between insulin action, the adrenergic nervous system (ANS), and lipid metabolism.

Calcium Antagonists and Thiazide Diuretics in the Treatment of Hypertension

The usefulness of the combination of nifedipine and chlorthalidone has been investigated in mild to moderate hypertensive patients (seven men, seven women; age range 39-62 years) by adding the diuretic to nifedipine monotherapy. After a 2 week washout, slow-release nifedipine 20 mg b.i.d. was given for 6 weeks, followed by addition of either chlorthalidone 25 mg (group A) or placebo (group B) q.d. for a further 6-week period. Blood pressure, heart rate, plasma renin activity, and 24-h urinary Na and K excretion were measured at baseline and at the end of each treatment period. Nifedipine decreased blood pressure in the two groups. A further significant fall was observed after chlorthalidone was added. No further change was detected after placebo in group B. Plasma renin activity after 1 h standardized walk significantly increased after combined treatment compared with baseline (3.3 +/- 1.2 to 9.4 +/- 5.3 ng/ml/h; p less than .05). No change was observed in 24 h urinary Na and K in the two groups. Venous distensibility measured by strain gauge plethysmography was slightly reduced during nifedipine monotherapy. Our data therefore suggest that chlorthalidone potentiates the antihypertensive effect of nifedipine despite an increase of renin activity.

Association of Hyperuricemia With Conventional Cardiovascular Risk Factors in Elderly Patients

The relationship between serum uric acid (UA) and cardiovascular risk profile was investigated in 557 outpatients (415 women) aged 60 years and older. Patients were grouped according to a UA cutoff level of 5.5 mg/dL. Prevalence of obesity, hypertension, and impaired glucose metabolism was increased in women with higher UA, who had higher body mass index (37.7±6.9 vs 33.1±5.9 kg/m2, P<.001), waist circumference, and serum glucose and triglyceride concentrations than women with lower UA levels. Conversely, men with higher UA levels showed lower high‐density lipoprotein cholesterol and higher left ventricular mass than men with lower UA levels. Estimated glomerular filtration rate was reduced in patients with high UA levels of both sexes (65±17 vs 72±16 mL/min/1.73 m2, P<.001, for women; 70±16 vs 76±15 mL/min/1.73 m2, P<.03, for men). Grouping patients by sex‐specific median UA concentrations produced similar results. These data indicate that, even in the elderly, UA clusters in a sex‐specific fashion with features of metabolic syndrome and signs of target organ damage.