L. Aldo Ferrara

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.

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.

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.

A Fast and Accurate Method for Genotyping the Angiotensin-Converting Enzyme I/D Polymorphism

To the Editor: The association of the insertion/deletion (I/D) polymorphism of the ACE gene with ischemic vascular disease is disputed.1 Mistyping as DD of 4% to 5% of ID subjects may contribute to conflicting findings.2 3 The original method4 preferentially extends allele D. The addition of 5% DMSO, or the use of an allele-specific oligonucleotide (ASO), reduces mistyping.5 6 Although the ASO technique is the method of choice,2 3 5 it is time consuming because a second nested PCR must be performed on the DD samples obtained with the original method. We have devised a one-step multiplex PCR, which we tested on 520 individuals and compared the results with …

The effects of nicardipine on sodium and calcium metabolism in hypertensive patients: a chronic study.

There is evidence in the literature that calcium entry blockers are able to affect calcium‐dependent hormone secretion and therefore can influence sodium and calcium metabolism.

Obesity and hypertensive heart disease: focus on body composition and sex differences

There is evidence that hypertension is frequently associated with overweight/obesity even in kids and adolescents. Either conditions influence development of left ventricular (LV) hypertrophy (LVH), through different biological and hemodynamic mechanisms: obesity is conventionally thought to elicit a coherent growth of LV chamber dimensions and myocardial wall thickness (eccentric LV geometry), whereas a more accentuated increase in wall-thickness (concentric LV geometry) is attributed to hypertension. While during youth these differences are visible, proportion of LV concentric geometry, the most harmful LV geometric pattern, sharply raises in obese individuals during middle age, and becomes the most frequent geometric patterns among obese-hypertensive individuals. Two conditions with elevated hemodynamic impact, severe obstructive sleep apnea and masked hypertension contribute to the development of such a geometric pattern, but non-hemodynamic factors, and specifically body composition, also influence prevalence of concentric LV geometry. Contrasting a general belief, it has been observed that adipose mass strongly influences LV mass, particularly in women, especially when fat-free mass is relatively deficient. Thus, though blood pressure control is mandatory for prevention and reduction of LVH in obese hypertensive patients, without reduction of visceral adiposity regression of LVH is difficult. Future researches should be addressed on (1) assessing whether LVH resulting from alteration of body composition carries the same prognosis as pressure overload LVH; (2) defining tissue characterization of the hypertrophic heart in obese-hypertensive patients; (3) evaluating whether assessment of hemodynamic loading conditions and biological markers can help defining management of the association of obesity with hypertension.

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.

Dietary Pattern and Blood Pressure Control in a Hypertension Outpatient Clinic

Although it is well known that some dietary measures are able to beneficially affect blood pressure (BP) levels, hypertensive patients find it very difficult to definitively change their nutritional habits. The aim of this study was to evaluate the effects on BP of a return to the habitual diet following a dietary intervention period. Three hundred and seven hypertensive patients (149 females, 158 males) with a mean age of 52±12 years were included in the study. All enrolled patients had reported having reverted to their habitual diet after a period of at least 6 months on a prescribed low-energy and/or low-sodium diet. Nutritional habits were investigated by a simple semiquantitative 24-item food-frequency questionnaire. Patients were divided into tertiles according to their systolic BP. The groups differed in regard to their body mass index (27.6±4, 28.7±4, and 30.4±6 kg/m2, respectively, for the low- to high-systolic BP groups, but were similar in regard to the number of antihypertensive pills taken (2.1±0.9, 2.2±1.2, 2.2±1.3) and metabolic parameters. Patients in the lowest tertile consumed a diet significantly lower in the percentage of energy from saturated fats and sodium content and significantly higher in the percentage of energy from carbohydrate, and the fiber and potassium content in comparison to the highest tertile. The number of servings of legumes, fish and cooked vegetables was higher and that of salami and cheese lower in the 1st tertile. Definitively changing a habitual diet to a healthier one is a difficult task for hypertensive patients. However, those who return to a diet richer in vegetables, legumes and fish and poorer in saturated fat and salt achieve better control of their BP, without increasing the number of antihypertensive pills.

Ambulatory monitoring of left ventricular function in patients with Parkinson's disease and postural hypotension

Left ventricular (LV) function was continuously monitored using a radionuclide detector (VEST) after intravenous injection of 25 mCi technetium-99m labelled red blood cells in nine patients with Parkinsons disease and postural hypotension (group 1) and ten patients with Parkinsons disease but without postural hypotension (group 2). LV function and blood pressure were monitored in the supine position for 15 min (period A), upon changing posture from the supine to the upright position for 10 min (period B), and upon returning to the supine position for 10 min (period C). In group 1, the passage from period A to period B induced a significant decrease in end-diastolic volume, end-systolic volume and ejection fraction (allP<0.01). In group 2, ejection fraction increased (P<0.05) upon changing posture from the supine to the upright position. Ejection fraction (F=33,P<0.01), end-diastolic volume (F=9,P<0.05) and end-systolic volume (F=10,P<0.05) were significantly different between the two groups. In group 1, stroke volume, cardiac output and vascular peripheral resistance decreased from period A to period B (allP<0.001). In group 2, no changes in stroke volume, cardiac output and vascular peripheral resistance were observed from period A to period B. All parameters were similar in the two groups during the periods A and C. Upon changing posture from the supine to the upright position, patients with Parkinsons disease and postural hypotension showed marked changes in parameters of LV function induced by vascular abnormalities. The results of this study may help to clarify the potential risk of sudden postural changes in such patients, which may cause fainting, syncope and increased risk of ischaemic coronary and cerebrovascular attacks and of lower limb fractures.