Effects Of Long-term Antihypertensive Treatment Research Articles

Effect of long-term antihypertensive treatment on cerebrovascular structure and function in hypertensive rats

Midlife hypertension is an important risk factor for cognitive impairment and dementia, including Alzheimer’s disease. We investigated the effects of long-term treatment with two classes of antihypertensive drugs to determine whether diverging mechanisms of blood pressure lowering impact the brain differently. Spontaneously hypertensive rats (SHR) were either left untreated or treated with a calcium channel blocker (amlodipine) or beta blocker (atenolol) until one year of age. The normotensive Wistar Kyoto rat (WKY) was used as a reference group. Both drugs lowered blood pressure equally, while only atenolol decreased heart rate. Cerebrovascular resistance was increased in SHR, which was prevented by amlodipine but not atenolol. SHR showed a larger carotid artery diameter with impaired pulsatility, which was prevented by atenolol. Cerebral arteries demonstrated inward remodelling, stiffening and endothelial dysfunction in SHR. Both treatments similarly improved these parameters. MRI revealed that SHR have smaller brains with enlarged ventricles. In addition, neurofilament light levels were increased in cerebrospinal fluid of SHR. However, neither treatment affected these parameters. In conclusion, amlodipine and atenolol both lower blood pressure, but elicit a different hemodynamic profile. Both medications improve cerebral artery structure and function, but neither drug prevented indices of brain damage in this model of hypertension.

ISH NIA PS 01-10 Short and Long-Term Effects of Antihypertensive Treatment on Human Retinal Arteriole Remodeling Evaluated with Adaptive Optics Camera

ISH NIA PS 01-10 Short and Long-Term Effects of Antihypertensive Treatment on Human Retinal Arteriole Remodeling Evaluated with Adaptive Optics Camera

Long-term effects of antihypertensive medications on bone mineral density in men older than 55 years.

IntroductionIn this study, we investigated the effects of long-term antihypertensive treatment with calcium channel blockers or beta blockers on the bone mineral density of maxilla, as determined by cone-beam computed tomography (CBCT).Material and methodsThis retrospective study was conducted on CBCT images of men older than 55 years who had received different dental indications. Data were grouped into three categories according to the antihypertensive medication history of the patients: group A included patients who had been taking beta-blocker treatment for more than 5 years, group B included patients who had been taking calcium channel blocker treatment for more than 5 years, and the control group included patients who had never used any hypertensive medications before.ResultsStatistically significant differences were observed between the beta blocker and calcium channel blocker groups.ConclusionIn hypertension treatment, beta blockers may be preferred to calcium channel blockers in patients at high risk for osteoporosis and bone resorption.

THE AFFECT OF THE REGRESSION OF THE LEFT VENTRICULAR HYPERTROPHY OF THE FUNCTIONAL CAPACITY IN HYPERTENSIVE PATIENTS: PP.35.487

The objective of our study was to evaluate the effects of long-term antihypertensive treatment (after 8 years) in left ventricular hypertrophy (LVH), physical working capacity and arrhythmogenic marcers (QTc interval dispersion). Methods: 73 hypertensive patients were analyzed (44 male, aged 55.4 ± 8 years and 29 female aged 57.3 ± 6 years) who were an antihypertensive treatment with echocardiographic LVH (left ventricular mass index: 163 ± 30.3 g/m2). Each subject underwent two-dimensional and Doppler echocardiography, 12-lead electrocardiogram examination and exercise stress testing (Bruce - protocol). Results: Decrease of index LVM (I group – regression LVH) was achieved in 37 pts (51% - 172.2 vs 142.08 g/m2; p < 0.005), while in 36 pts it was increased (II group – progression LVH) (49% - 152.5 vs 158.7; ns). The reduction was due to a decrease in septal (13.4 vs 12.3; p < 0.05) and posterior wall thickness (11.4 vs 10.7 vs 1.2; p < 0.03), without changes in LV diameter. In patients of the I group ratio of the velocity time integrals of »E to »A mitral waves increase (E/A before Th 0.83 vs 0.92, p < 0.05). Patients with reduction of the left ventricular mass could be shown a significant reduction of QT dispersion from 64.9 ± 21.8 to 51.1 ± 15.9 ms (p < 0.009), opposite the patients with progression LVH (49.5 ± 14.5 vs 45 ± 12.5; ns). After regression LVH (I group), the functional capacity was increase (6.35 vs 7.56 METs; ns), decrease maximum systolic BP (205.7 vs 201.6 mmHg, ns), decrease peak double products (26.8 vs 26.2, ns), and significantly decrease double product/METs (2.6 vs 1.9, p < 0.05) in third minuts while it remained unchanged in pts of the II group. Conclusion: LVH regression in our patients was achieved by the decrease of wall thickness of the left ventricle and it is followed by the improvement of the functional capacity and by the reduction of QT dispersion.

Cardiac structural and functional changes during long-term antihypertensive treatment with lacidipine and atenolol in the European Lacidipine Study on Atherosclerosis (ELSA)

To evaluate and correlate the effects of long-term antihypertensive treatment on left ventricular (LV) mass and carotid structural changes in a large group of essential hypertensive patients, participating in the European Lacidipine Study on Atherosclerosis (ELSA). In four (Brescia, Glasgow, Naples and Pisa) of 23 centres participating in the ELSA study, an echocardiographic examination was performed at baseline and repeated, until the end of the 4-year study, in essential hypertensive patients, followed-up for carotid quantitative ultrasound examination of intima-media thickness (IMT), after random allocation to treatment with either lacidipine or atenolol (and added hydrochlorothiazide, as required for control of blood pressure). M-mode, two-dimensional guided echocardiography was used to measure left ventricular (LV) wall thickness and dimensions, from which LV mass was calculated, using an anatomically validated formula (Penn Convention) and indexed to body surface area (left ventricular mass index, LVMI). The echocardiographic tracings were blindly evaluated in a single reading centre (Brescia). Bilateral IMT was measured at the site of common carotid and bifurcation far walls (CBMmax). At baseline, cardiac and carotid ultrasound scans were available in 278 patients (mean age 54 +/- 7 years, 57% males, 22% obese). A significant correlation was observed between baseline LVMI and CBMmax (r = 0.22, P < 0.001), independent of age. In multivariate analysis, CBMmax and mean 24-h pulse pressure were most strongly associated with baseline LVMI. A significant reduction in LVMI was observed both during lacidipine (n = 96) (-12.5% reduction) and atenolol (n = 78) (-13.9% reduction) treatments (up to 4 years) (P < 0.001 for both, without significant differences between treatments). Changes in LVMI were not related to changes in carotid wall thickness. In multivariate analysis, baseline LV mass and mean 24-h systolic blood pressure changes were significantly associated with changes in LV mass. In this large, long-term controlled study, antihypertensive treatment with atenolol or lacidipine was accompanied by a similar and significant decrease in LV mass. Treatment-induced changes in LV mass were related to baseline LV mass and changes in 24-h mean systolic blood pressure, without any correlation with changes in carotid structure. In the whole ELSA population, carotid IMT changes have been shown to be unrelated to blood pressure reduction, but significantly influenced by the type of antihypertensive treatment.

Effect of the Antihypertensive Treatment on the Bone Mineral Density and Osteoporotic Fracture

The financial and social cost of hypertension and osteoporosis, clinically silent diseases, are determined by the consequences, such as a vascular disease and fractures. The relationship between these illnesses has not been clearly established, although many alterations in extracellular metabolism of calcium, which could determine the level of bone mineral density (BMD) in these patients, have been associated to hypertension. Despite these alterations, the lack of studies relating these two important diseases is surprising, and hypertension is not identified as a risk factor for osteoporosis. Interestingly, there is a lack of information of the long-term effects of antihypertensive treatment on bone mineral density, although 50 % of the hypertensive population is made up of postmenopausal women. Most studies analyzed the effects of thiazides and, to a lesser degree, the effects of calcium antagonist. The purpose of this review is evaluate the effect of the antihypertensive therapeutic group (diuretics, β-blockers, calcium antagonists, angiotensin converting enzyme) on the bone mineral density (BMD) and osteoporotic fracture. Keywords: hypertension, osteoporosis, thiazides, bloqueantes, antagonistas del clacio, aceis

Effects of valsartan and nifedipine coat-core on systemic arterial stiffness in hypertensive patients

The aim of this study was to compare the effects of long-term antihypertensive treatment on brachial-ankle pulse wave velocity (PWV), a marker of systemic arterial stiffness, between angiotensin II receptor blocker valsartan and long-acting calcium channel blocker nifedipine coat-core. Forty-one patients (54 +/- 3 years of age, 20 men and 21 women) with essential hypertension (155 +/- 3/95 +/- 3 mm Hg) were randomly allocated to the treatment with valsartan (80 mg once daily) or nifedipine coat-core (20 mg once daily). Brachial-ankle PWV and 24-h ambulatory blood pressures (BP) were measured before and 3 months after treatment. Baseline data did not differ between the valsartan and nifedipine groups. The PWV also was similar between the groups (1669 +/- 65 v 1622 +/- 64 cm/sec). Three months of treatment similarly reduced resting systolic and diastolic BP (nifedipine, -18.4 +/- 4.2/-11.9 +/- 2.7 mm Hg; valsartan, - 17.4 +/- 3.3/-9.8 +/- 2.1 mm Hg, all P < .001). The PWV was significantly reduced compared with baseline values in the valsartan group (-195 +/- 42 cm/sec, P < 0.001) but not in the nifedipine group (-69 +/- 40 cm/sec, NS). The 24-h mean heart rate increased in the nifedipine group but remained unchanged in the valsartan group, although BP were similarly lowered for 24 h. A tachycardic response was associated with an increase or lesser reduction in PWV in a group treated with nifedipine (r = 0.584, P < .01). These data suggest that long-term treatment with valsartan could reduce arterial stiffness better than nifedipine-coat core. The favorable vascular effect of valsartan was due in part to its nonhypotensive effect. The expected decrease in arterial stiffness may be offset by reflex sympathetic activation in some patients treated with nifedipine.

D78 Long-term effects of anti-hypertensive treatment on bi-ventricula mass and function

D78 Long-term effects of anti-hypertensive treatment on bi-ventricula mass and function

Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy.

To evaluate the effects of long-term antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril on structural alterations and the endothelial function of small resistance arteries in hypertensive patients with left ventricular hypertrophy. Fourteen patients with left ventricular hypertrophy were treated for 3 years with a lisinopril-based regimen. Patients underwent an echocardiographic evaluation of left ventricular mass index at baseline, during the first and third years of treatment. At the end of the treatment period, subcutaneous small resistance arteries (obtained by biopsy of the subcutaneous fat from the gluteal region) were dissected and mounted on a micromyograph (Mulvany's technique); the media : lumen ratio was then calculated. Data obtained were compared with those observed for 14 untreated essential hypertensive patients and 14 normotensive subjects, age- and sex-matched. In the present study, a significantly lower media : lumen ratio was observed in treated compared with untreated hypertensive patients, although it remained significantly higher than that in normotensive subjects. In treated hypertensive patients a significant reduction in clinic blood pressure was observed. However, their blood pressure remained significantly higher than that in normotensive subjects. Significant correlations between the media : lumen ratio and blood pressure, left ventricular mass index or changes in left ventricular mass index during treatment were observed. The response to acetylcholine administration was reduced in untreated hypertensives compared with that in normotensives. In patients treated with lisinopril, the vasodilatation obtained with the two higher doses of acetylcholine was greater than that in untreated hypertensives, thus suggesting an improvement of endothelial function. Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.

Implications of the links between hypertension and myocardial infarction for choice of drug therapy in patients with hypertension

Meta-analyses of major outcome trials have demonstrated that the benefits of antihypertensive treatment for reduction of the incidence of stroke are entirely consistent with the benefits predicted from epidemiologic data; however, there remains a shortfall in the expected reduction of the incidence of coronary heart disease. Several explanations have been proffered to account for this shortfall, including the potential deleterious metabolic effects of long-term antihypertensive treatment; this has led to the speculation that antihypertensive agents with beneficial ancillary properties might confer additional significant advantage. However, with the exception of the angiotensin-converting enzyme inhibitors, few of these agents have translated into clinical benefit for humans. In addition, sound reasons exist to justify a focus on maintaining and improving the "quality" of blood pressure control. Current evidence suggests that optimal benefit is likely to result from the use of pharmacologic strategies that lower blood pressure consistently over a 24-hour period while at the same time maintaining the "normal" circadian pattern of blood pressure. This result will only be achieved with drugs and drug regimens that genuinely offer long duration of action with the additional potential benefit of maintaining a significant blood pressure lowering effect beyond the end of the dosage interval. This factor is particularly important because many patients with hypertension demonstrate poor adherence to prescribed dosage regimens.

Benidipine Improves Endothelial Function in Renal Resistance Arteries of Hypertensive Rats

We studied the effects of long-term antihypertensive treatment on endothelial function in renal resistance arteries from spontaneously hypertensive rats (SHR). Wistar-Kyoto rats (WKY) were used as a normotensive reference. Adult SHR were treated with benidipine (a calcium antagonist) or ecarazine (a vasodilator) for 10 weeks; the drugs caused similar reductions in blood pressure. Changes in isometric tension of rings prepared from the third-order branches of the renal arteries were recorded. Endothelium-dependent relaxations induced by acetylcholine in rings contracted with norepinephrine were smaller in SHR than in WKY. The impaired relaxation was improved by benidipine treatment, but ecarazine had no significant effect. In vitro treatment with meclofenamic acid, a cyclooxygenase inhibitor, did not alter the differences in the relaxations. In the presence of meclofenamic acid, N omega-nitro-L-arginine methyl ester slightly reduced the relaxations; the relaxation was smaller in SHR than in WKY and was not affected by benidipine treatment. In rings contracted with 40 mmol/L. KCI, the relaxations induced by acetylcholine in the presence of meclofenamic acid were smaller than those in rings contracted with norepinephrine. The relaxation was smaller in SHR than in WKY but was normalized by benidipine treatment. Thus, acetylcholine relaxes rat renal resistance arteries by releasing nitric oxide and endothelium-derived hyperpolarizing factor from the endothelium, which is impaired in SHR. Long-term benidipine treatment improves the impaired relaxation in SHR by enhancing nitric oxide-mediated relaxation.

Effect of manidipine and delapril on insulin sensitivity in type 2 diabetic patients with essential hypertension

The open trial was designed to evaluate the effects of long-term antihypertensive treatment with the calcium-channel blocker, manidipine and the angiotensin converting enzyme (ACE) inhibitor, delapril on insulin sensitivity in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients with essential hypertension. We measured the insulin sensitivity index (S I) and the glucose-effectiveness (S G) by the use of Bergman's minimal model method in 18 hypertensive NIDDM patients before and after administration of manidipine (group A) or delapril (group B) for 3 months. Manidipine treatment for 3 months significantly improved S I in group A from 3.35 ± 0.61 (× 10 −4 min −1 μU −1 ml −1) to 4.70 ± 1.34 ( P < 0.05). Delapril treatment for 3 months also significantly improved S I in group B from 3.56 ± 1.04 to 5.00 ± 0.87 ( P < 0.05). Manidipine significantly improved S G in group A from 1.60 ± 0.64 (× 10 −2 min) to 2.19 ± 0.38 ( P < 0.05). Delapril treatment also significantly improved S G in the group B from 1.41 ± 0.56 to 1.91 ± 0.35 ( P < 0.05). Manidipine and delapril did not affect urinary C-peptide excretion for 24 h in the hypertensive NIDDM patients. Treatment with manidipine or delapril significantly reduced systolic and diastolic blood pressures in the hypertensive NIDDM patients. There were no differences between plasma glucose, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions, heart rate and body weight after 3 months on manidipine or delapril. This study confirmed the improving effects on S I and S G by long-term treatment with manidipine or delapril in the hypertensive NIDDM patients.

Long-term effects of antihypertensive treatment and good glycemic control on plasma lipids in diabetic rats

The long-term effects of angiotensin-converting enzyme inhibitors (captopril and enalapril), calcium-entry blockers (diltiazem and nicardipine), and good glycemic control on plasma lipids and lipoproteins were studied in streptozotocin diabetic rats. Diabetic rats had increased plasma cholesterol, tryiglycerides, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterol, and decreased levels of high-density lipoprotein (HDL) cholesterol than in normal rats. Compared to other antihypertensives, nicardipine seems to have a less beneficial effect on lipids and lipoproteins. However, it is only the good glycemic control that normalized these plasma lipids and lipoproteins in diabetic rats. This suggests that good glycemic control prevents dyslipidemia in diabetic rats. The observed beneficial effects of antihypertensives were unrelated to either food or water intake.

Effect of Long-Term Antihypertensive Treatment on the Cerebral Blood Flow in Patients with Brain Infarction

After long-term antihypertensive treatment (mean 25 months, range 18–38 months), the cerebral blood flow (CBF) in both symptomatic and asymptomatic hemispheres remained unchanged despite a reduction in blood pressure in 24 hypertensive cases with chronic cerebral infarction. However, there was a positive correlation between the change in systolic or mean blood pressure and the change in CBF in the symptomatic hemisphere (p < 0.05). Our data suggest that more than 80% of the pretreatment level of blood pressure or 120 mm Hg of systolic blood pressure might be a preferable lower level of blood pressure for antihypertensive treatment in patients with chronic cerebral infarction.

P-480 - Effects of long-term antihypertensive treatment with AE0047, a novel Ca antagonist, on cerebrovascular autoregulation and hypertrophy in spontaneously hypertensive rats

P-480 - Effects of long-term antihypertensive treatment with AE0047, a novel Ca antagonist, on cerebrovascular autoregulation and hypertrophy in spontaneously hypertensive rats

The Effect of Antihypertensive Treatment on Electrocardiogram Voltages in the EWPHE Trial

Long-term effects of antihypertensive treatment on various electrocardiogram (ECG) voltages and the association between ECG findings at randomization and subsequent mortality were evaluated in the double-blind, placebo-controlled trial of elderly hypertensive patients, conducted by the European Working Party on High Blood Pressure in the Elderly (EWPHE). Patients were treated with a combination of hydrochlorothiazide and triamterene or matching placebo; methyldopa or placebo was added if blood pressures remained high. RaVL and SV1 + RV5 at randomization were related to systolic blood pressure (SBP) and RaVL was also related to diastolic blood pressure (DBP), after adjustment for age, gender, and body mass index (BMI). When adjusted for age and body mass index, the decreases in RaVL and SV1 + RV5 were not correlated with the changes in SBP after 1 year of active treatment but the decreases in SV1 + RV5 were positively related to the fall in DBP. After 4 years of active treatment, the fall in SBP was associated with decreases in RaVL and in SV1 + RV5, after adjustment for age and changes in BMI.

Effects of Long-Term Antihypertensive Treatment With Tertatolol on Diastolic Function in Hypertensive Patients With and Without Left Ventricular Hypertrophy

We assessed the effects of long-term antihypertensive treatment with 5 mg tertatolol, a noncardioselective beta-blocker, on left ventricular hypertrophy (LVH) and diastolic function. Fifteen hypertensive patients were selected as good responders to previous treatment with tertatolol (supine blood pressure less than 140/90 mm Hg). They were divided into 2 groups: group 1 with LVH (n = 6) and group 2 without LVH (n = 9). After a one month wash-out period, all patients received 5 mg tertatolol once daily. In case of uncontrolled blood pressure (BP), the dose was doubled after 2 weeks in 10 patients. BP control was obtained in all patients. M-mode echocardiography and Doppler-echocardiography were performed under controlled conditions after BP normalization and after 6 months of treatment. Long-term BP normalization significantly reduced left ventricular mass index (LVMI) in group 1 (from 137 +/- 3 to 121 +/- 3 g/m2, P less than .01), but not in group 2 (from 120 +/- 3 to 114 +/- 4 g/m2, P = NS). After 2 weeks of effective therapy, the ratio between early and late diastolic peak flow velocity across the mitral valve (E/A ratio), significantly increased in both groups (from 0.72 +/- 0.04 to 0.87 +/- 0.06 in group 1, P less than .05; and from 1.13 +/- 0.06 to 1.26 +/- 0.07 in group 2, P less than .05). After 6 months, together with the reduction of LVMI, a further increase of E/A ratio was only observed in group 1 (to 1.30 +/- 0.12, P less than .05). (1) LVH contributes to left ventricular diastolic dysfunction in hypertensive patients since its reversal is able to improve diastolic filling, and (2) effective antihypertensive treatment with tertatolol improves diastolic function independently from its effect on LV mass.

Cardiovascular and renal effects of long-term antihypertensive treatment

To study whether restoration of a normal circulatory system could be achieved with antihypertensive treatment, 13 hypertensive men with structural cardiovascular changes and 37 normotensive control subjects were investigated by echocardiography, apexcardiography, plethysmography, inulin and p-amino-hippurate clearance, and determination of 24-hour urinary excretion of albumin, first at age 49 years and again seven years later. All men were untreated at the first investigation. Immediately thereafter, therapy with the cardioselective beta-adrenoceptor blocker metoprolol tartrate was initiated in the hypertensive men. Seven years of antihypertensive treatment resulted in (1) normalization of central and peripheral hemodynamic variables, (2) reversal of left ventricular hypertrophy in proportion to achieved blood pressure control, (3) normalization of systolic wall stress and a well-preserved systolic left ventricular function, (4) normalization of diastolic left ventricular function, and (5) normalization of increased microalbuminuria and a decrease in renal vascular resistance, with no change in glomerular filtration rate compared with control subjects. In conclusion, the findings strongly indicate that regression of cardiovascular structural changes can be achieved with long-term antihypertensive treatment.

Cardiovascular and Renal Effects of Long-term Antihypertensive Treatment

To study whether restoration of a normal circulatory system could be achieved with antihypertensive treatment, 13 hypertensive men with structural cardiovascular changes and 37 normotensive control subjects were investigated by echocardiography, apexcardiography, plethysmography, inulin and p-amino-hippurate clearance, and determination of 24-hour urinary excretion of albumin, first at age 49 years and again seven years later. All men were untreated at the first investigation. Immediately thereafter, therapy with the cardioselective beta-adrenoceptor blocker metoprolol tartrate was initiated in the hypertensive men. Seven years of antihypertensive treatment resulted in (1) normalization of central and peripheral hemodynamic variables, (2) reversal of left ventricular hypertrophy in proportion to achieved blood pressure control, (3) normalization of systolic wall stress and a well-preserved systolic left ventricular function, (4) normalization of diastolic left ventricular function, and (5) normalization of increased microalbuminuria and a decrease in renal vascular resistance, with no change in glomerular filtration rate compared with control subjects. In conclusion, the findings strongly indicate that regression of cardiovascular structural changes can be achieved with long-term antihypertensive treatment.

Hypolipidemic effects of long-term antihypertensive treatment with captopril: A prospective study

In 27 hypertensive patients already receiving antihypertensive treatment and with serum total cholesterol levels between 260 and 350 mg/dl, captopril in a dosage of 50 mg twice a day was substituted for one of the drugs they were taking. Patients taking a diuretic continued the same diuretic at the same dosage. After six months of therapy that included captopril, patients resumed their former therapy. Diet and physical activity remained unchanged during the study. Biochemical and blood pressure determinations were performed before captopril was begun, after three and six months of captopril therapy, and three months after the former therapy was resumed. During the regimens that included captopril, the triglyceride value was reduced from 249 to 184 mg/dl (p <0.05), the total cholesterol level decreased from 287 to 237 mg/dl (p <0.005), and the high-density lipoprotein cholesterol value rose from 40 to 51 mg/dl (p <0.005). The reduction in cholesterol was unrelated to blood pressure changes or to changes in serum triglyceride, glucose, or potassium levels. Treatment regimens that included captopril also induced a greater diastolic blood pressure reduction than regimens that did not include captopril. The antihypertensive efficacy of a therapeutic regimen that includes captopril, along with its favorable effect on lipid profile, could be useful in preventing cardiovascular complications in hypertensive patients.