The DASH trials implicate dysfunction in calcium regulation in the pathogenesis of human hypertension.
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Calcium↗
Biomedical subjects
A G Logan
Publications and source records attributed to A G Logan.
High prevalence of unrecognized sleep apnoea in drug-resistant hypertension.
OBJECTIVES: To determine the prevalence of obstructive sleep apnoea (OSA) in adult patients with drug-resistant hypertension, a common problem in a tertiary care facility. DESIGN: Cross-sectional study. SETTING: University hypertension clinic. PATIENTS AND METHODS: Adults with drug-resistant hypertension, defined as a clinic blood pressure of > or = 140/90 mmHg, while taking a sensible combination of three or more antihypertensive drugs, titrated to maximally recommended doses. Each of the 41 participants completed an overnight polysomnographic study and all but two had a 24 h ambulatory blood pressure measurement. RESULTS: Prevalence of OSA, defined as an apnoea-hypopnoea index of > or = 10 obstructive events per hour of sleep, was 83% in the 24 men and 17 women studied. Patients were generally late middle-aged (57.2 +/- 1.6 years, mean +/- SE), predominantly white (85%), obese (body mass index, 34.0 +/- 0.9 kg/m2) and taking a mean of 3.6 +/- 0.1 different antihypertensive medications daily. OSA was more prevalent in men than in women (96 versus 65%, P = 0.014) and more severe (mean apnoea-hypopnoea index of 32.2 +/- 4.5 versus 14.0 +/- 3.1 events/h, P = 0.004). There was no gender difference in body mass index or age. Women with OSA were significantly older and had a higher systolic blood pressure, lower diastolic blood pressure, wider pulse pressure and slower heart rate than women without OSA. CONCLUSIONS: The extraordinarily high prevalence of OSA in these patients supports its potential role in the pathogenesis of drug-resistant hypertension, and justifies the undertaking of a randomized controlled trial to corroborate this hypothesis.
Adult↗
Rationale and design of the Canadian Continuous Positive Airway Pressure Trial for Congestive Heart Failure patients with Central Sleep Apnea--CANPAP.
BACKGROUND: Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is commonly observed in patients with congestive heart failure (CHF), in which it is an independent risk factor for death. Treating CSR-CSA may, therefore, improve outcomes in patients with CHF. OBJECTIVE: The Canadian Continuous Positive Airway Pressure Trial for Congestive Heart Failure Patients with Central Sleep Apnea (CANPAP) is a multicentre, randomized, controlled clinical trial designed to test the hypothesis that treating CSR-CSA with continuous positive airway pressure (CPAP) will reduce the combined rate of all-cause mortality and cardiac transplantation in patients with CHF. Secondary outcomes include the severity of CSR-CSA, left ventricular volumes and function, submaximal exercise capacity, quality of life and hospital admissions. PATIENTS AND METHODS: The aim is to enroll 408 patients with CHF (New York Heart Association class II to IV and left ventricular ejection fraction of less than 40%) and CSR-CSA over a five-year period. Patients are randomly assigned to either standard medical therapy for CHF or standard medical therapy plus CPAP. The trial has 80% power to detect a 35% between-group treatment difference for the all-cause mortality-cardiac transplantation rate. Substudies will assess the role of oximetry as a screening tool for detecting CSR-CSA in patients with CHF, and the effects of CPAP on cardiac arrhythmias and plasma concentrations of natriuretic peptides and catecholamines. CONCLUSIONS: The CANPAP trial will help to define the role of CPAP better as a nonpharmacological intervention for the treatment of patients with CHF who have CSR-CSA.
Canada↗
Effects of continuous positive airway pressure on cardiovascular outcomes in heart failure patients with and without Cheyne-Stokes respiration.
BACKGROUND: Continuous positive airway pressure (CPAP) improves cardiac function in patients with congestive heart failure (CHF) who also have Cheyne-Stokes respiration and central sleep apnea (CSR-CSA). However, the effects of CPAP in CHF patients without CSR-CSA have not been tested, and the long-term effects of this treatment on clinical cardiovascular outcomes are unknown. METHODS AND RESULTS: We conducted a randomized, controlled trial in which 66 patients with CHF (29 with and 37 without CSR-CSA) were randomized to either a group that received CPAP nightly or to a control group. Change in left ventricular ejection fraction (LVEF) from baseline to 3 months and the combined mortality-cardiac transplantation rate over the median 2.2-year follow-up period were compared between the CPAP-treated and control groups. For the entire group of patients, CPAP had no significant effect on LVEF, but it was associated with a 60% relative risk reduction (95% confidence interval, 2% to 64%) in mortality-cardiac transplantation rate in patients who complied with CPAP therapy. Stratified analysis of patients with and without CSR-CSA revealed that those with CSR-CSA experienced both a significant improvement in LVEF at 3 months and a relative risk reduction of 81% (95% confidence interval, 26% to 95%) in the mortality-cardiac transplantation rate of those who used CPAP. CPAP had no significant effect on either of these outcomes in patients without CSR-CSA. CONCLUSIONS: CPAP improves cardiac function in CHF patients with CSR-CSA but not in those without it. Although not definitive, our findings also suggest that CPAP can reduce the combined mortality-cardiac transplantation rate in those CHF patients with CSR-CSA who comply with therapy.
Aged↗
Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis.
BACKGROUND: We investigated the relation between fetoplacental growth and the use of oral antihypertensive medication to treat mild-to-moderate pregnancy hypertension. METHODS: The study design was a metaregression analysis of published data from randomised controlled trials. Data from a paper that was regarded as an extreme statistical outliner were excluded from primary analyses. The change in (group) mean arterial pressure (MAP) from enrolment to delivery was compared with indicators of fetoplacental growth. FINDINGS: Greater mean difference in MAP with antihypertensive therapy was associated with the birth of a higher proportion of small-for-gestational-age (SGA) infants (slope: 0.09 [SD 0.03], r2=0.48, p=0.006, 14 trials) and lower mean birthweight significant after exclusion of data from another paper regarded as an extreme statistical outliner (slope: -14.49 [6.98] r=0.16, p=0.049, 27). No relation with mean placental weight was seen (slope -2.01 [1.62], r2=0.15, p=0.25, 11 trials). INTERPRETATION: Treatment-induced falls in maternal blood pressure may adversely affect fetal growth. Given the small maternal benefits that are likely to be derived from therapy, new data are urgently needed to elucidate the relative maternal and fetal benefits and risks of oral antihypertensive drug treatment of mild-to-moderate pregnancy hypertension.
Antihypertensive Agents↗
Sodium sensitivity, not level of salt intake, predicts salt effects.
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Age Factors↗
Hypertension aggregates in families of kidney stone patients with high urinary excretion of uric acid.
OBJECTIVE: To determine whether kidney stone disease (KSD) and hypertension (HTN) share a common familial component that is determined by a specific urinary biochemical abnormality. DESIGN: Familial aggregation study. PATIENTS: Two hundred and twelve KSD patients, aged 18-50 years, collected a 24-h urine sample to measure the urinary excretion of uric acid, calcium, oxalate, magnesium and citrate, and were interviewed about the occurrence of HTN among first-degree relatives. OUTCOME: Positive family history (FHx) of HTN defined as two or more relatives with HTN, and HTN occurring in the fathers, mothers and siblings. RESULTS: Positive FHx of HTN was significantly associated with increasing urinary excretion of uric acid (P = 0.03) but not with the excretion of the other substances. When the patients were divided into those with and without hyperuricosuria, the adjusted odds ratio (OR) for positive FHx of HTN in a hyperuricosuric KSD patient was 3.8 (95% CI, 1.22-11.66). Separate analysis on the occurrence of HTN in the fathers, mothers and siblings of the probands indicated that hyperuricosuria is positively related to HTN occurring in the siblings of the patients (P < 0.001) but not in the fathers or in the mothers. The adjusted OR for HTN occurring in siblings of hyperuricosuric patients compared with siblings of non-hyperuricosuric patients was 3.8 (2.12-6.67). CONCLUSION: Siblings of KSD patients with hyperuricosuria had a significantly increased prevalence of HTN that could not be accounted for by age, family size, body-mass index and personal history of HTN of the probands. Additional studies need to be undertaken to determine whether this familial clustering has a genetic or environmental origin.
Adult↗
Statistical issues in a metaregression analysis of randomized trials: impact on the dietary sodium intake and blood pressure relationship.
In a meta-analysis of randomized trials of the effects of dietary sodium interventions on blood pressure, we found substantial heterogeneity among the studies. We were interested in evaluating whether measurement error, known to be a problem for dietary sodium measures, publication bias, or confounding factors could be responsible for the heterogeneity. A measurement error correction was developed that corrects both the slope and the intercept and takes into account the sample size of each study and the number of measurements taken on an individual. The measurement error correction had a minimal effect on the estimates, although it performed well in simulated data. A smoothed scatter plot was used to assess publication bias. Metaregressions provide a convenient way to jointly assess the effects of several factors, but care must be taken to fit an appropriate model.
Bias↗
Study duration and validity.
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Diet, Sodium-Restricted↗
1999 Canadian recommendations for the management of hypertension. Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension.
OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals on the management of hypertension in adults. OPTIONS: For patients with hypertension, there are both lifestyle options and pharmacological therapy options that may control blood pressure. For those patients who are using pharmacological therapy, a range of antihypertensive drugs is available. The choice of a specific antihypertensive drug is dependent upon the severity of the hypertension and the presence of other cardiovascular risk factors and concurrent diseases. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: MEDLINE searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (January 1993 to May 1998). Reference lists were scanned, experts were polled and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to levels of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS: Harms and costs: The diagnosis and treatment of hypertension with pharmacological therapy will reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and mortality. RECOMMENDATIONS: This document contains detailed recommendations pertaining to all aspects of the diagnosis and pharmacological therapy of hypertensive patients. With respect to diagnosis, the recommendations endorse the greater use of non-office-based measures of blood pressure control (i.e., using home blood pressure and automatic ambulatory blood pressure monitoring equipment) and greater emphasis on the identification of other cardiovascular risk factors, both in the assessment of prognosis in hypertension and in the choice of therapy. On the treatment side, lower targets for blood pressure control are advocated for some subgroups of hypertensive patients, in particular, those with diabetes and renal disease. Implicit in the recommendations for therapy is the principle that for the vast majority of hypertensive patients treated pharmacologically, practitioners should not follow a stepped-care approach. Instead, therapy should be individualized, based on consideration of concurrent diseases, both cardiovascular and noncardiovascular. VALIDATION: All recommendations were graded according to the strength of the evidence and the consensus of all relevant stakeholders. SPONSORS: The Canadian Hypertension Society and the Canadian Coalition for High Blood Pressure Prevention and Control.
Adult↗
L-deprenyl in Alzheimer's disease: cognitive and behavioral effects.
BACKGROUND: Short-term studies of L-deprenyl in Alzheimer's disease (AD) suggest a beneficial effect, whereas longer-term studies are less convincing. Accordingly, we undertook a 6-month, randomized, double-blind, placebo-controlled clinical trial to assess the potential benefit of L-deprenyl in AD. METHODS: Sixty subjects were assigned to L-deprenyl (10 mg daily) or placebo. After 4 weeks of single-blind placebo, 51 subjects entered the double-blind phase. The Brief Psychiatric Rating Scale (BPRS) was the primary outcome measure. Secondary outcome measures were the Mini-Mental State Examination, Global Deterioration Scale, Alzheimer's Disease Assessment Scale (noncognitive), Cornell Scale for Depression in Dementia, Buschke Selective Reminding Test (BSRT), Relative's Assessment of Global Symptomatology-Elderly (RAGS-E), Controlled Oral Word Association Test, and Modified Continuous Performance Test. In addition, several exploratory tasks were included for future hypothesis testing. RESULTS: We found no significant differences between the L-deprenyl and placebo groups on the primary or secondary measures. However, several measures appeared to be sensitive to change over time, including the total score on the BPRS and some of its components as well as parts of the BSRT and the RAGS-E. CONCLUSION: Oral L-deprenyl provides no detectable benefit on general behavior, neuropsychiatric symptoms, or cognitive function in AD after 6 months of treatment. Protocols for future drug studies should utilize measures that are sensitive to change over time such as the BPRS.
Aged↗
A randomized controlled trial to assess the incidence of new onset hypertension in patients after shock wave lithotripsy for asymptomatic renal calculi.
PURPOSE: To answer the question of whether extracorporeal shock wave lithotripsy (ESWL*) induces hypertension, a prospective, randomized controlled trial of normotensive patients with asymptomatic renal calculi was designed. MATERIALS AND METHODS: Patients were randomized to receive immediate ESWL versus observation, reserving ESWL for the onset of symptoms. The rates of new onset hypertension were evaluated for both groups. RESULTS: There was no observed difference in the incidence of hypertension between the treatment and observation groups. CONCLUSIONS: The risk of hypertension in patients undergoing ESWL therapy is similar to that of a control cohort of initially observed asymptomatic patients.
Adult↗
Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites.
OBJECTIVE: Large volume paracentesis is an effective treatment for refractory ascites, but the need for routine infusion of albumin or other volume expanders remains controversial. The aim of this study was to assess the short term effects of a single 5-L paracentesis without albumin replacement on total central blood volume, systemic and renal hemodynamics, sodium homeostasis, and neurohumoral factors. PATIENTS AND METHODS: Twelve patients with biopsy-proven cirrhosis and tense, diuretic-resistant ascites were studied before and 48 h after a single 5-L paracentesis without albumin infusion. Systemic hemodynamics and total central blood volume were assessed using radionuclide angiography. Glomerular filtration rate and effective renal plasma flow were measured by inulin and para-aminohippurate clearances, respectively. Lithium clearance was used as an index of proximal tubular reabsorption of sodium. In addition, plasma concentrations of neurohumoral factors were determined. RESULTS: Total central blood volume was 2.41 +/- 0.33 L/m2 (mean +/- SEM) before and 2.34 +/- 0.18 L/m2 48 h after large volume paracentesis (p = 0.76). Similarly, no differences were detected in the cardiac index, glomerular filtration rate, effective renal plasma flow, urinary sodium excretion, hematocrit, plasma renin activity, or concentrations of plasma aldosterone, norepinephrine, or atrial natriuretic factor. CONCLUSIONS: A single large volume paracentesis without albumin replacement causes no disturbances in systemic and renal hemodynamics 48 h after the procedure. These results suggest that a single 5-L paracentesis without albumin infusion is a safe and satisfactory short term option for the management of patients with cirrhosis and tense, diuretic-resistant ascites.
Aged↗
Dietary salt restriction increases vascular insulin resistance.
BACKGROUND: Recent studies have shown that insulin has a direct vasodilator effect and that vascular sensitivity to insulin is impaired in hypertension. How the vasodilator effect of insulin is regulated physiologically is unknown. It has been appreciated that salt restriction may have adverse effects on glucose and lipid metabolism--processes regulated by insulin. To determine whether dietary salt restriction might affect vascular sensitivity to insulin, we studied 13 subjects (including eight borderline hypertensive subjects and five normotensive subjects) after 1 week of a normal sodium diet (240 mEq/day) and after 1 week of a low-sodium diet (20 mEq/day) with a randomized, double-blind crossover design. METHODS AND RESULTS: Vascular sensitivity to insulin was assessed with the dorsal hand vein linear variable differential transformer technique. When the "normal" salt diet was given, vascular sensitivity for insulin was significantly less (i.e., dose that produced the half-maximal response [ED50] insulin was higher) in hypertensive subjects (ED50 insulin for hypertensive subjects, 5.75 milliunits (mU)/min; ED50 insulin for normotensive subjects, 0.23 mU/min; p < 0.05). Vascular sensitivity to insulin was inversely correlated with mean arterial pressure and plasma norepinephrine concentration. When the low salt diet was given, vascular sensitivity to insulin decreased in both the normotensive and hypertensive groups, paralleling an increase in plasma norepinephrine. Blood pressure was not significantly decreased by reducing salt intake. CONCLUSION: In these younger normotensive and hypertensive subjects, dietary salt restriction increases resistance to the vasodilating effects of insulin.
Adult↗
Accurate measurement of impaired glomerular filtration using single-dose oral cimetidine.
To improve the validity of a timed creatinine clearance as a measure of glomerular filtration rate (GFR), we investigated whether a single 800-mg dose of oral cimetidine was sufficient to inhibit tubular secretion of creatinine (TScr). Forty-five 3-hour timed creatinine clearances (Clcr) with single 800-mg dose oral cimetidine (TCC) in 17 renal transplant recipients with marked renal function impairment (creatinine 2.0 to 7.1 mg/dL) were compared with simultaneous [125I]-iothalamate GFR (Cliothal). For comparison, 13 timed Clcr without cimetidine (TC), and 36 24-hour Clcr were performed. The TCC was the most accurate: the ratio (mean +/- SD) of TCC:Cliothal was 1.12 +/- 0.02, compared with 1.33 +/- 0.08 for Clcr:Cliothal and 1.53 +/- 1.02 for TC:Cliothal. The difference between Cliothal and TCC was small over the range of GFRs tested (mean +/- 2 SD), 0.9 +/- 2.5 mL/min/1.73 m2. The intraclass correlation (R) for within-subject reproducibility of the TCC in five subjects was 0.8 (95 percent CI; 0.5, 0.9), and in 11 subjects who had at least three GFR determinations over 24 weeks, the TCC was as responsive to change in GFR as Cliothal. There was an inverse relationship between fractional excretion of cimetidine and GFR (r2 = -0.70), suggesting increased tubular secretion of cimetidine with decreasing GFR. In conclusion, a single 800-mg oral dose of cimetidine was effective in inhibiting TScr such that the TCC was an accurate, reproducible, and responsive test of GFR.
Administration, Oral↗
Effect of hyperglycaemia on arterial pressure, plasma renin activity and renal function in early diabetes.
1. In insulin-dependent diabetes mellitus, hyperglycaemia has a profound effect on renal and systemic haemodynamic function. The mechanism for this is unknown. 2. We conducted a study in 11 males with insulin-dependent diabetes mellitus, within 6 years of diagnosis. We examined the neurohumoral, haemodynamic and renal variables during euglycaemia (4.0-6.0 mmol/l) and after a 12 h period of hyperglycaemia (8.5-10.5 mmol/l). Subjects were examined in a sodium-replete state during supine rest and during simulated orthostatic stress induced by lower body negative pressure at -15 mmHg. 3. Variations in glycaemia markedly influenced plasma renin activity, which was increased at baseline during hyperglycaemia (3.82 +/- 0.66 pmol of angiotensin I h-1 ml-1 compared with 2.13 +/- 0.33 pmol of angiotensin I h-1 ml-1 during euglycaemia, P = 0.009), and rose further during simulated orthostatic stress. Mean arterial pressure was also elevated during hyperglycaemia (89 +/- 2 mmHg compared with 81 +/- 3 mmHg during euglycaemia, P = 0.03), both at rest and during orthostatic stress. 4. The renal haemodynamic effects of hyperglycaemia included maintenance of glomerular filtration rate in the face of significant declines in renal blood flow, and a probable increase in filtration fraction (0.21 +/- 0.01 compared with 0.18 +/- 0.01 during euglycaemia, P = 0.06). The responses of mean arterial pressure and renal blood flow to simulated orthostatic stress were not affected by hyperglycaemia, but the forearm vascular response was significantly augmented. 5. These data suggest that sustained hyperglycaemia activates the renin-angiotensin system, thereby increasing systemic and renal vasomotor tone. Over time such changes may have deleterious microvascular consequences.
Adult↗
Is knowing your cholesterol number harmful?
To examine the potential adverse psychological effects of screening for hypercholesterolemia, 287 men working at a motor-car assembly or steel-making plant who were ultimately diagnosed as having hypercholesterolemia and 236 randomly selected normal cholesterol controls from the same plants completed psychological questionnaires at the initial screen and 1-year later. At baseline and before diagnosis, hypercholesterolemic men scored higher on mental health and lower on negative affect than controls (p values < 0.05). One year later no adverse changes on the psychological measures were found irrespective of the type of follow-up care that they were randomly assigned to receive. Surprisingly only about half of the hypercholesterolemic men believed they had hypercholesterolemia at follow-up despite being told otherwise. Baseline scores of those who did not accept the label (n = 122) [classified as deniers] were higher on measures of positive affect and lower on measures of negative effect than those of hypercholesterolemic men who accepted the disease label (n = 73) (p values < 0.05). Moreover they held more negative attitudes towards dietary change at baseline (p < 0.03), made fewer dietary changes (p values < 0.05), and had a lesser change in total cholesterol. We conclude that a hypercholesterolemia detection and treatment program conducted in a working adult population had no adverse psychological consequences. It did, however, reveal a large subset of hypercholesterolemic men who did not accept the label despite being told they had this problem. Denial was a significant barrier to health behaviour change and may represent a maladaptive coping style for men at risk of cardiovascular disease. High cholesterol appears to be associated with better mental health and those who deny having hypercholesterolemia have the best mental health. The multifarious relationship between cholesterol, mental health, and denial deserves further study.
Adult↗
Effect of insulin on the venoconstrictive response to norepinephrine in normal human subjects: the influence of sodium status.
Hyperinsulinemia and insulin resistance have been implicated in the pathogenesis of essential hypertension, with alterations in insulin-induced vasodilatation as one possible mechanism. The aims of this study were to assess the local vasodilatory action of insulin on a dorsal hand vein and the influence of sodium status on the insulin effect in healthy human subjects. Distensibility of a superficial hand vein and response to norepinephrine, insulin, and nitroglycerine were measured by the linear variable differential technique. Fourteen healthy subjects were studied after a low (20 mmol) and high (200 mmol) sodium diet for 7 days. All subjects gained weight (P < .005) and had higher central venous pressure (P = .003) on a high sodium intake. Baseline mean arterial pressure, heart rate, and fasting plasma glucose levels were not significantly different between the two diets. High sodium diet, however, resulted in a higher calculated insulin/glucose ratio (P = .029) implying reduced tissue sensitivity to insulin. Baseline plasma norepinephrine was significantly higher on the low (1.29 +/- 0.13 nmol/L) compared with the high sodium diet (0.79 +/- 0.11 nmol/L) (P < .005). The dorsal hand vein was significantly more dilated at the baseline level on a low sodium (2.60 +/- 0.12 mm) than on a high sodium diet (2.20 +/- 0.12 mm) (P = .034). However, the maximal constriction achieved with norepinephrine was not significantly different between the two diets. Only an insulin dose of 0.8 mU/min on a low sodium diet was able to significantly dilate the norepinephrine preconstricted vein (77 +/- 9% of baseline diameter versus ED50) (P = .002).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗