Orthostatic hypotension and vitamin D deficiency in older adults: systematic review and meta-analysis.

BACKGROUND: Over the latest years different studies have investigated the possible relationship between D deficiency and occurrence of orthostatic hypotension (OH), often reaching controversial results. We perform an update meta-analysis providing an update overview on the association between hypovitaminosis D and orthostatic hypotension (OH) in older adults. METHODS: Data extraction was independently performed by two authors and based upon predefined criteria. The meta-analysis was performed using a random-effects model. Statistical heterogeneity between groups was measured using the Higgins I2 statistic. RESULTS: Eight investigations enrolling 16.326 patients (mean age 75.5 years) met the inclusion criteria and were considered for the analysis. Patients with vitamin D deficiency were more likely to have OH compared to those without (OR: 1.36, 95% CI 1.14-1.63, p = 0.0001, I2 = 43.6%). A further sub-analysis, based on three studies, estimating the risk of OH in patients with hypovitaminosis D receiving antihypertensive treatment, did not reach the statistical significance (OR: 1.40, 95% CI 0.61-3.18, p = 0.418, I2 = 53.3%). Meta-regression performed using age (p = 0.12), BMI (p = 0.73) and gender (p = 0.62) as moderators did not reveal any statistical significance in influencing OH. Conversely, physical activity, Vitamin D supplementation and use of radioimmunoassay for the measurement of vitamin D serum levels showed a significant inverse relationship towards the risk of OH (Coeff.-0.09, p = 0.002, Coeff. - 0.12, p < 0.001 and Coeff. - 0.08, p = 0.03, respectively) among patients with hypovitaminosis D. A direct correlation between the administration of antihypertensive treatment and the risk of OH in older patients with low vitamin D level was observed (Coeff. 0.05, p < 0.001). CONCLUSIONS: Hypovitaminosis D is significantly associated with OH in older adults and directly influence by the administration of antihypertensive drugs. Conversely, physical activity, vitamin D supplementation and use of radioimmunoassay as analytic method inversely correlated with the risk of OH in older patients.

Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension.

Background Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2±8.2 years and mean Mini-Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo ( P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI]=1.1 [0.8-1.5], P=0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7±13.8% versus 7.3±11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02017340.

Hypovitaminosis D and orthostatic hypotension: a systematic review and meta-analysis.

OBJECTIVES: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). METHODS: A systematic literature search of major electronic databases from inception until 09/2015 was made for articles providing data on orthostatic hypotension and hypovitaminosis D. A random effects meta-analysis of cross-sectional studies investigating orthostatic hypotension prevalence comparing participants with vs. those without hypovitaminosis D was undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 317 initial hits, five cross-sectional studies were meta-analysed including 3646 participants (1270 with hypovitaminosis D and 2376 without). The participants with hypovitaminosis D had a higher prevalence of orthostatic hypotension (OR = 1.88; 95% CI: 1.25-2.84; I = 68%) that was not affected by adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13-3.68; I = 73%). People with orthostatic hypotension had significantly reduced serum vitamin D concentrations (standardized mean difference = -0.42; 95% CI: -0.72 to -0.12). One longitudinal study confirmed the association between hypovitaminosis D and orthostatic hypotension. CONCLUSION: Our meta-analysis highlights that hypovitaminosis D is associated with orthostatic hypotension, independent of potential confounders. Further longitudinal studies and clinical trials are required to confirm these findings.

Vitamin D and orthostatic hypotension.

INTRODUCTION: we aimed to investigate on the potential relationship between vitamin D and orthostatic hypotension (OH) in a case-control model in older adults. METHODS: all participants were community-dwelling adults who were not taking vitamin D supplements. Cases were subjects aged 64 or older who were diagnosed with OH at a Falls and Blackout Unit. Controls were age- (within 5 years) and gender-matched subjects who had no history of blackouts, falls or orthostatic dizziness in the preceding year. OH was defined according to standard criteria and was diagnosed with an active stand test. Serum vitamin D [25(OH)D] was measured by radioimmunoassay. RESULTS: seventy-six subjects were included in the analysis (38 controls and 38 cases). Twenty-four in each group were female and mean age was between 78 and 79 years. Subjects with OH had lower serum 25(OH)D compared to controls (mean difference = 20.6 nmol/l, P = 0.0002). Lower vitamin D status was associated with an increased risk of OH after adjustment for season, body mass index, presence of stroke, diabetes and angina (P = 0.035) but not with impaired orthostatic haemodynamics. DISCUSSION: findings suggest that vitamin D may play a role in the aetiology of OH. Further studies will be required to explore on this relationship.

Determinants of a positive response to carotid sinus massage and head-up tilt testing.

BACKGROUND: Orthostatic hypotension (OH) and carotid sinus hypersensitivity (CSH) are common causes of syncope in older people. The aim of this study was to determine if patient's age, sex and presenting symptoms influence the result of carotid sinus massage and head-up tilt testing. METHODS: Retrospective analysis of the database and reports was carried out between 1995 and 2006 at a tertiary referral centre. Patient's age, sex, presenting symptoms and test result were examined. Presenting symptoms were classified as syncope, falls or dizzy spells. RESULTS: Of the 1583 tests reported, OH was present in 402 patients (25.4%), of whom 175 (11.1%) were symptomatic. 188 of 1464 (12.8%) patients undergoing carotid sinus massage had evidence of CSH, of which 156 were symptomatic. Male patients were significantly more likely to have symptomatic CSH than female patients (odds ratio 2.28, 95% CI 1.54 to 3.04, p<0.01). There were non-significant trends to increased diagnosis of symptomatic OH with increasing age, male sex and referral with syncope. There were non-significant trends to increased diagnosis of symptomatic CSH with increasing age and referral with syncope. CONCLUSION: Male sex, increasing age and being referred with syncope were all associated with an increased likelihood of receiving a diagnosis of either OH or CSH. The overall prevalence of CSH was lower than in previous studies, which may reflect different patient populations.

[Efficacy and safety of a herbal drug containing hawthorn berries and D-camphor in hypotension and orthostatic circulatory disorders/results of a retrospective epidemiologic cohort study]. / Wirksamkeit und Verträglichkeit eines pflanzlichen Arzneimittels mit Weissdornbeeren und D-Campher bei hypotonen und orthostatischen Kreislaufregulationsstörungen. Ergebnisse einer retrospektiven epidemiologischen Kohortenstudie.

BACKGROUND AND OBJECTIVE: Korodin Herz-Kreislauf-Tropfen, a herbal drug containing D-camphor (CAS 76-22-2; 2.5 %) and a liquid extract of fresh hawthorn berries (97.3%), has been used since many years for the treatment of orthostatic hypotension. The combination as well as its constituents were tested in clinical trials against placebo with healthy volunteers and patients using tilt-tests. The objective of this study was to investigate efficacy and safety of the drug under the conditions of medical practice in comparison to other drugs admitted for this indication. PATIENTS AND METHODS: The study was performed as an epidemiological retrospective cohort study in 46 medical practices in Germany. In the practices the files were reviewed for patients who were treated between 1st January 2000 and 31st December 2002 for orthostatic hypotension. Included in the study were all patients who were treated either with the test drug or a control drug containing etilefrine, oxilofrine, midodrine, norfenefrine or dihydroergotamine and who met the inclusion criteria. The data of the files were coded, transferred to case report forms and augmented by the physician's statements about symptoms and success. Effect criteria were the improvement of symptoms and change of blood pressure during treatment. The correctness of the data was controlled using anonymous copies of the files. A total of 490 patients (399 in the test-group and 91 in the control group) between 11 and 102 years were included in the study. To correct heterogeneities in baseline conditions, treatment results were adjusted by regression and stratification to equal baseline conditions using the propensity score. RESULTS: The adjusted odds ratio for improvement was 5.6, the adjusted mean increase of the systolic blood pressure the 2-fold compared to the control group. The difference was highly significant and did not depend on age or initial blood pressure. In the test group two adverse events were observed which had no relation to the medication; in the control group one reversible event with a probable relation to the medication was observed. CONCLUSIONS: The test drug was proven as effective and safe in the treatment of orthostatic hypotension in medical practice for all age groups and independent of the initial blood pressures.