Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia.

Although there is little information from primary or secondary prevention trials on cholesterol-lowering medication in diabetic patients, the reduction of elevated cholesterol is widely recommended for this group. The American Diabetes Association (ADA) recommends drug therapy in diabetic patients if low density lipoprotein (LDL)-cholesterol remains at > 130 mg/dl, or > 100 mg/dl in patients with macroangiopathy, after dietary intervention. When cholesterollowering medication is indicated, the choice of the drug must take into account the other lipid abnormalities that are often present and the need to maintain optimal glycaemic control. In the present study we compared the efficacy and safety of the novel HMG-CoA reductase inhibitor atorvastatin at the dose of 10 mg/day with simvastatin , lovastatin and pravastatin at doses of 10, 20 and 20 mg/day, respectively, and placebo, in type 2 diabetic patients with moderate elevation of LDL-cholesterol with or without elevation of triglycerides. All the quoted agents are enzyme inhibitors effective in lowering LDL-cholesterol in humans. The efficacy endpoints were the mean per cent changes in plasma LDL-cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol concentrations from baseline to the end of treatment (24 weeks). Atorvastatin at a dose of 10 mg/day produced: (1) a significant reduction in LDL-cholesterol (-37%) in comparison with equivalent doses of simvastatin (-26%), pravastatin (-23%), lovastatin (-21%), and placebo (-1%); (2) HDL-cholesterol increases (7.4%) comparable to or greater than those obtained with simvastatin (7.1%), pravastatin (3.2%), lovastatin (7.21%), and placebo (-0.5%); (3) a significantly greater reduction in total cholesterol (- 29%) than that obtained with simvastatin (-21%), pravastain (-16%), lovastatin (-18%), and placebo (1%); and (4) a significantly greater reduction in triglycerides than that obtained with all the other drugs and placebo. In all treatment groups no significant variation in fibrinogen concentration was observed. All reductase inhibitors studied had similar levels of tolerance. There were no incidents of persistent elevations of serum aminotransferases or myositis.

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.

Cardiovascular abnormalities in never-treated hypertensives according to nondipper status.

Ambulatory blood pressure monitoring allows a better understanding of blood pressure fluctuations over 24 h than simple clinic measurements. In this way the diagnosis of "white coat" versus "sustained" hypertension and that of "dipper" (patient with blood pressure fall during nighttime > 10% of daytime levels) versus "nondipper" status were made possible. This pilot study has been undertaken to investigate whether patients with recently discovered, never-treated, mild, sustained hypertension have cardiovascular abnormalities according to their dipper/nondipper status. Patients with long-standing (n = 123) and newly discovered (n = 56) sustained hypertension were classified according to their nighttime blood pressure fall, and compared with normotensive controls. Ambulatory blood pressure monitoring was performed noninvasively. Parameters of left ventricular structure, cardiac systolic and diastolic function, and carotid anatomy were determined noninvasively by echographic methods. Significant increases in parameters of cardiac structure as well as abnormalities in diastolic function were observed in patients with long-standing hypertension, regardless of their dipper status. In the group with newly discovered hypertension, left atrium (3.4+/-0.3, 3.7+/-0.5, 3.2+/-0.4 cm in dippers, nondippers, and controls, respectively), end-diastolic diameter index (2.9+/-0.3, 3.0+/-0.2, 2.8+/-0.2 cm/m), and atrial filling fraction (0.50+/-0.07, 0.52+/-0.05, 0.42+/-0.04) were significantly altered only in the nondipper subgroup, in comparison with controls. Significant changes in cardiac structure and diastolic function were observed in nondipper patients with recently discovered hypertension, who, at variance with dippers, show changes similar to those in patients with long-standing hypertension. Hypertensives with the observed abnormalities may benefit from active antihypertensive treatment, which appears, therefore, justified even in an early phase of mild hypertension, in terms of potential reduction of end-organ complications as well as cost-effectiveness.

Isolated office hypertension and end-organ damage.

BACKGROUND: Patients with elevated blood pressure levels in the doctor's office but normal blood pressures at other times have recently been described as having 'isolated office hypertension' (IOH). There is debate concerning whether this condition is really benign and thus not in need of treatment. Most of the previous studies on this topic included patients who had already been administered antihypertensive treatment, which unavoidably alters their cardiovascular profile. OBJECTIVE: To evaluate whether recently discovered and never-treated patients with isolated office hypertension have structural or functional abnormalities in comparison with normotensive controls. METHODS: Patients included in the study underwent 24 h ambulatory blood pressure monitoring, M-mode echocardiography and high-resolution echography of carotid arteries. Parameters of lipid and carbohydrate metabolism were also determined. RESULTS: We investigated 76 patients (20 with IOH and 56 with sustained hypertension) who had recently been diagnosed hypertensive but never been administered antihypertensive treatment and 32 matched controls. No changes were detected in left ventricular mass (LVM h2.7, 41.5 +/- 11, 44.5 +/- 10 and 41.5 +/- 10 g/cm2.7 in IOH, sustained hypertension and controls, respectively) and in intimal-medial thickness (IMT, 0.54 +/- 0.13, 0.59 +/- 0.14 and 0.55 +/- 0.16 mm, respectively). However, the left ventricular diastolic function was significantly different (E/A = 1.08 +/- 0.3, 1.04 +/- 0.3 and 1.43 +/- 0.3, respectively, P = 0.02) and the carotid diameter significantly lower than that expected from the pressure-diameter relationship for normotensives. CONCLUSIONS: These results, at variance with those of others, suggest that IOH affects the cardiovascular system even during the early phases of the disease and indicate the need for prospective clinical trials to evaluate the benefit from early treatment of IOH patients.

Effects of Isradipine on 24-h Blood Pressure, Left Ventricular Hypertrophy and Hemodynamics in Type II Diabetic Hypertensive Patients.

The effects of 5 mg slow-release isradipine given once daily for both office-taken and monitored 24-h blood pressure, left ventricular mass and forearm hemodynamics have been evaluated by noninvasive methods for 6 months in 12 type II diabetic patients aged 40--60 years with concomitant arterial hypertension of mild to moderate degree. A significant reduction in both supine (from 164/96 to 146/85 mmHg) and standing blood pressure (from 164/100 to 143/89 mmHg) was observed at the end of the treatment period. A slight reduction was detected in walking blood pressure and a more marked reduction in sleeping blood pressure measured by an ambulatory blood pressure monitoring system, although the statistical significance was only approached because of the huge daily variability in blood pressure levels. A significant reduction in left ventricular mass index was detected by M-mode echocardiography (from 153 plus minus 72 to 122 plus minus 84 g/m(2) body surface area) without any impairment of left ventricular systolic function. Brachial artery compliance was not significantly increased (from 1.86 plus minus 0.7 to 2.21 plus minus 0.9 cm(4) center dot dyne(minus sign1) center dot 10(7)) and impedance slightly but nonsignificantly reduced (from 99.6 plus minus 52 to 65.7 plus minus 13 dyne(5) center dot cm(minus sign5) center dot 10(2)) by the treatment. These results show that long-term isradipine treatment reduces blood pressure values and left ventricular hypertrophy. However, the findings of this study need to be confirmed in a larger population sample in order to establish whether isradipine really improves the overall cardiovascular risk profile.

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.

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)

Cardiovascular response to adrenergic stimulation during treatment with tertatolol. A new non-cardioselective beta-blocking agent in primary hypertensive patients.

The antihypertensive effects of tertatolol, a new non-cardioselective beta-blocking drug, were investigated in 20 patients with mild to moderate primary arterial hypertension, in a placebo controlled double blind randomized study. After tertatolol 5 mg o.d. significant decreases in both systolic and diastolic blood pressure and in heart rate were observed at rest (BP from 155/103 +/- 3/1 to 139/91 +/- 4/3 mmHg p less than 0.01; HR from 79 +/- 2 to 60 +/- 2 bpm p less than 0.01). Peak blood pressure, heart rate and myocardial O2 consumption, indirectly measured as cardiac workload, determined during adrenergic stimulation by 70 degrees head-up tilt, cold pressor test, mental arithmetic stress, isometric exercise and bicycle exercise were also reduced by 4 weeks of tertatolol treatment in comparison to pretreatment levels. No significant changes in the same parameters were induced by placebo. No side effects were observed during treatment.

[Cardiovascular response to the cold test in obese subjects. Effect of a hypocaloric, normal sodium diet]. / Risposta cardiovascolare al "test al freddo" in soggetti obesi. Effetto della dieta ipocalorica normosodica.

Loss of weight in obese patients, both hypertensive and normotensive, causes a fall in blood pressure (BP) through a mechanism which is still not fully understood. The effects of a low-sodium low-energy diet on BP were assessed in 20 obese subjects (15 M and 5 F; age 26-65 years), 11 of whom were normotensive and 9 hypertensive. Following a period of normocaloric diet, a diet of 600 kcal was prescribed for 6 months. BP and heart rate (HR) were measured at the start and end of hypocaloric diet in resting conditions and during stimulation of the adrenergic nervous system (ANS) obtained by exposure to cold (immersion of the hand in water and ice). A reduction of resting BP (from 137/81 +/- 5/4 to 122/74 +/- 4/4 mmHg, p less than 0.05) was observed in 8 patients who lost at least 30% of excess weight (from kg 107 +/- 6 to 91 +/- 4, p less than 0.001) together with an increase in BP during exposure to cold (from 140/82 +/- 3/3 to 156/95 +/- 7/4 mmHg before and from 120/78 +/- 3/4 to 140/88 +/- 3/3 after the diet, p less than 0.05). No changes were found in the daily urinary excretion of Na during the course of diet therapy. These results demonstrate that a hypocaloric diet, independent of saline restriction, is able to reduce resting BP and pressure peaks during adrenergic stimulation.