Use of antihypertensives and the risk of Parkinson disease. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. Antihypertensive agents and risk of Parkinson's disease, essential tremor and dementia: a population-based prospective study (NEDICES). Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial. Appropriate Blood Pressure Control in NIDDM (ABCD) Trial. Pharmacist involvement in primary care improves hypertensive patient clinical outcomes. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Post-stroke antihypertensive treatment study. A preliminary result. L-type calcium channel blockers and Parkinson disease in Denmark.
Recent studies related angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers to possible neuroprotective effects. Little is known about neuroprotection of angiotensin II (AT II) antagonists or beta-blockers.
                To explore the association between antihypertensive drug use and the risk of developing a first-time diagnosis of Parkinson disease (PD).
                This was a case-control analysis within the UK-based General Practice Research Database. Cases were >or=40 years of age with an incident PD diagnosis between 1994 and 2005. We matched one control to each PD case on age, sex, general practice, index date, and duration of previous history in the database. We assessed antihypertensive drug use by timing and by exposure duration. We calculated ORs using conditional logistic regression, adjusted for body mass index, smoking, and various cardiovascular, metabolic, and psychiatric diseases and dementia.
                We identified 3,637 cases with a first-time diagnosis of idiopathic PD and an equal number of matched controls. As compared to nonuse of antihypertensive drugs, the adjusted OR for current use of >or=30 prescriptions was 1.08 (95% CI 0.85 to 1.37) for ACE inhibitors, 0.91 (95% CI 0.41 to 2.00) for AT II antagonists, 1.16 (95% CI 0.95 to 1.41) for beta-blockers, and 0.77 (95% CI 0.63 to 0.95) for calcium channel blockers.
                Current long-term use of calcium channel blockers was associated with a significantly reduced risk of a Parkinson disease diagnosis, while the risk was not materially altered for users of angiotensin converting enzyme inhibitors or beta-blockers and, with less statistical precision, for users of angiotensin II antagonists. To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension.
                Multicenter, randomized, double-blind, placebo-controlled.
                Community-based ambulatory population in tertiary care centers.
                4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black.
                --Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d.
                Primary. Nonfatal and fatal (total) stroke. Secondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures.
                Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87.
                In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000. Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson's disease (PD) or dementia. There are no data for essential tremor (ET).
                To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease).
                Prospective population-based study in Spain enrolling 5,278 participants at baseline.
                Use of antihypertensive medications (aside from beta-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not associated with prevalent or incident PD. Calcium channel blocker use was marginally reduced in prevalent dementia cases (OR(adjusted) = 0.63, p = 0.06) but was not associated with reduced risk of incident dementia (RR(adjusted) = 1.02, p = 0.95).
                We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders.
                Copyright 2009 S. Karger AG, Basel. National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy. The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is a large, prospective, randomized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus (NIDDM) designed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in NIDDM. The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and an angiotensin-converting-enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations aged 40-74 years, 470 hypertensive patients (diastolic blood pressure of > or = 90.0 mmHg at time of randomization) and 480 normotensive patients (diastolic blood pressure of 80.0 mmHg at time of randomization). The study duration is 5 years and is scheduled to end in May of 1998. Patients are randomized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary. The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance. Secondary outcome measures are urinary albumin excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. Given the data showing the impact of hypertension on complications in NIDDM, the ABCD Trial is designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM. The practice of pharmaceutical care in primary care settings in Thailand is currently not generally accepted.
                To evaluate the effect of pharmacist involvement in treatment with hypertensive patients in primary care settings.
                The treatment objective was to stabilize the blood pressure (BP) of hypertensive patients in accordance with the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure guidelines. Patients were randomly assigned to a pharmacist-involved group (treatment) or a group with no pharmacist involvement (control). Pre- and post-test BPs, tablet counts, lifestyle modifications, and pharmacists' recommendations were recorded. The 6-month study was carried out in Mahasarakham University pharmacy and 2 primary care units. Patients were monitored monthly by reviewing their medications and supported by providing pharmaceutical care and counseling.
                From a total of 235 patients, the treatment group (n = 118) had a significant reduction in both systolic (S) and diastolic (D) BP compared with the 117 patients of the control group (p = 0.037, 0.027, respectively). The 158 patients (76 treatment, 82 control) with BPs >or=140/90 mm Hg at the beginning of the study showed significant BP reductions (p = 0.002 SBP, 0.008 DBP). The proportion of 158 patients whose BP became stabilized was higher in the treatment group (p = 0.017). The treatment group showed significantly better adherence (p = 0.014) and exercise control (p = 0.012) at the end of the study. Physicians accepted 42.72% of medication modifications and 5.34% of the suggestions for additional investigations.
                Hypertensive patients who received pharmacist input achieved a significantly greater benefit in BP reduction, BP control, and improvement in adherence rate and lifestyle modification. We investigated whether nonsteroidal antiinflammatory drug use was associated with a lower risk for Parkinson's disease (PD) in a large cohort of US men and women. PD risk was lower among ibuprofen users than nonusers. Compared with nonusers, the relative risks were 0.73 for users of fewer than 2 tablets/week, 0.72 for 2 to 6.9 tablets/week, and 0.62 for 1 or more tablets/day (p trend = 0.03). No association was found between the use of aspirin, other nonsteroidal antiinflammatory drugs, or acetaminophen and PD risk. The results suggest that ibuprofen use may delay or prevent the onset of PD. Post-stroke Antihypertensive Treatment Study (PATS) was a randomized, double-blind and placebo-controlled trial, which aimed at determining whether antihypertensive treatment could reduce the risk of fatal and nonfatal stroke incidence in patients with a history of stroke or transient ischemic attack (TIA). 5,665 patients were randomized by a sealed envelope system. Systolic blood pressure (SBP) ranged from 80 to 280 mm Hg and diastolic (DBP) from 50 to 150 mmHg. The average SBP was 154 mmHg and average DBP 93 mmHg. The mean age was 60 years. Among the patients, women accounted for 28%. In 71% the latest stroke was ischemic. Average follow-up approximated to 2 years. The three-year average SBP was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment group, and the three-year DBP was 89 mmHg and 87 mmHg respectively. The three-year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients placebo treatment and 9.4 per 100 with indapamide. The relative risk by proportional hazards regression analysis was 0.71 (P = 0.0009). For deaths from all causes, the relative risk was 0.91. (P > 0.05). The findings of this trial indicate that in patients with a history of stroke or TIA, blood pressure reduction of 5/2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal and nonfatal stroke by 29%, with three-year absolute benefit of 29 events per 1000 participants. This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood-brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk.
                We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis.
                Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54-0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications.
                Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers.
There is currently a lack of evidence for the use of antihypertensive drugs for either the primary or secondary prevention of PD. More observational studies are required to identify potential drugs to go forward for safety and tolerability studies in people with early PD. The results of the ongoing trial will help inform further research.