CONTROLLED COMPARISON OF EFFECTS OF EXERCISE AND ALCOHOL ON BLOOD PRESSURE AND SERUM HIGH DENSITY LIPOPROTEIN CHOLESTEROL IN SEDENTARY MALES

1. Seventy-two sedentary male drinkers, aged 20-45 years, and with mean blood pressure (BP) at entry of 132 +/- 1.2/73 +/- 0.9 mmHg, completed a 4 week study during which they were assigned randomly to either drink a low alcohol beer (effectively reducing their weekly alcohol intake from 481 +/- 47 mL to 52 +/- 5 mL) or to continue their normal drinking habits. 2. Within these two groups subjects were further assigned to either a moderate exercise programme of three 30 min sessions per week of stationary cycling at 60-70% maximum workload or to a control light exercise programme where they pedalled against zero or minimal resistance. 3. Both alcohol restriction and moderate exercise were associated with mean falls in bodyweight of 0.5 kg. After adjustment for bodyweight a significant main effect of alcohol restriction on systolic BP (-4.1 +/- 1.7 mmHg, P less than 0.05) and diastolic BP (-1.6 +/- 0.8 mmHg, P = 0.05) was demonstrated. There was no significant main effect of moderate exercise on systolic or diastolic blood pressure despite a significant improvement in physical fitness (maximal oxygen uptake increasing from 33.2 +/- 0.8 mL/kg per min to 35.5 +/- 0.1 mL/kg per min). 4. Significant falls in high density lipoprotein cholesterol (HDLC) and triglyceride levels seen with alcohol restriction were unaffected by the increase in fitness, the magnitude of the fall being similar in both the moderate and light exercise groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

EFFECT OF SEX-RELATED CHANGES IN BLOOD PRESSURE AT ENTRY TO THE MRC TRIAL ON PREDICTION OF CARDIOVASCULAR RISK

1. Using the MRC trial placebo group as the data source, we examined relationships between cardiovascular risk, gender, and blood pressure (BP) at screening, on entry to the trial, and after 3 months of follow up. 2. Blood pressure on entry to the trial (162/98 mmHg) was significantly higher than at the second screening (154/95 mmHg) visit and at 3 months (144/91 mmHg). The entry BP was higher, and the changes from screening to entry and from entry to 3 months were greater in females. Females had a low cardiovascular risk, but because of the greater changes of BP at entry they were over-represented at the top of the entry BP distribution, whereas males were over-represented at the bottom. The result of these effects was that the relationship between cardiovascular risk and entry BP was shifted to the right and was flatter than the corresponding curves measured at screening or after 3 months of follow up. 3. In consequence, the severity of hypertension in the trial population was overestimated from measurement of BP at entry, and the capacity of trial entry BP to predict cardiovascular risk was weakened. 4. BP on entry to the MRC Trial was affected by a pressor effect that diminished the value of BP as a cardiovascular risk factor because it differentially affected sub-populations by gender.     

A multicountry controlled trial of strategies to promote dissemination and implementation of brief alcohol intervention in primary health care: findings of a World Health Organization collaborative study

OBJECTIVE: This study examines the impact of marketing strategies on the dissemination of a brief alcohol intervention program to general practitioners (GPs). The marketing strategy was tested to determine the most effective way to promote awareness about and consideration of a brief alcohol intervention program. The study also examines the impact of training and support strategies to promote the program's implementation in routine primary care. METHOD: A pragmatic trial was carried out in Australia, Belgium (Flanders), Denmark, England, New Zealand and Spain (Catalonia) in which GPs were randomly allocated into one of three marketing conditions (direct mail, telemarketing and academic detailing [personal visits]). The GPs who requested a brief intervention program and agreed to use it were stratified by previous marketing condition and randomly allocated into one of three implementation strategy groups: written guidance, outreach training and outreach training plus ongoing telephone support. RESULTS: Acceptance of the brief intervention program was more effective with use of telemarketing (65%) and academic detailing (67%) than with direct mail (32%) for promoting awareness about and consideration of a brief alcohol intervention program. The median proportion of patients screened was higher for trained GPs (6%) and supported GPs (9%) than for control GPs (1%), who received only written guidance on how to conduct brief intervention. Similarly, the median rate for giving advice to at-risk patients was higher for trained GPs (3%) and supported GPs (3%) than for control GPs (0%). CONCLUSIONS: The adoption of more direct approaches for disseminating evidence-based intervention programs to GPs is a necessary first step for changing practice behavior. However, outreach training was required to promote actual use of a new procedure in routine practice.     

General practitioner participation in the second Australian National Blood Pressure Study (ANBP2)

1. The second Australian National Blood Pressure Study (ANBP2) is an outcome trial of the treatment of hypertension in the elderly conducted entirely in general practices across Australia. Prior to ANBP2, no study of this size and nature had been undertaken in Australian general practice and the response of General Practitioners (GPs) to becoming involved in long-term cardiovascular research was unknown. 2. Academic departments and Divisions of General Practice were approached to support the project. General Practitioners were approached by letter of invitation and contacted by a regional medical coordinator (RMC) either at a face-to-face meeting or by telephone. 3. At the close of recruitment to ANBP2, 1938 GPs from 950 practices had registered as investigators. Sixty-two Divisions of General Practice were approached to support the study in five mainland Australian states with 39 (63%) participating, although participation by state was highly variable (range: 18-100%). Thirty divisional or promotional dinner meetings were held, with 56% (368/658) of those attending registering as investigators. Of the 8098 GPs sent a letter of invitation to participate in the study, 1357 (17%) expressed interest and eventually enrolled as investigators, ranging from 8% in Queensland to 28% in New South Wales. Ninety-six per cent of GPs who had a personal face-to-face contact (696/724) with the RMC registered in the study. 4. The GP recruitment phase of ANBP2 has been successfully completed. Peer-to-peer recruitment was the most successful strategy; however, success varied between states. General Practitioner recruitment to long-term clinical trials appears to be successful with a multifactorial approach focusing on peer-to-peer recruitment.     

COMPARISON OF OSCILLOMETRIC BLOOD PRESSURE MEASUREMENTS AT THE WRIST WITH AN UPPER-ARM AUSCULTATORY MERCURY SPHYGMOMANOMETER

1. Oscillometric devices for blood pressure (BP) measurement at the wrist are becoming more widely used in clinical practice. However, systematic comparisons with standard auscultatory BP measurement at the brachial artery are scarce. Therefore, we compared two such devices, the Boso-Mediwatch (Bosch & Sohn GmbH U. Co., Jungingen, Germany) and the Omron R3 (Omron Corp., Tokyo, Japan), with upper-arm auscultatory mercury sphygmomanometry. 2. In 20 normotensive subjects and 20 treated hypertensive subjects, the Boso-Mediwatch was applied to the left wrist by observer 1 and was compared with mercury sphygmomanometry of the right upper arm by observer 2. Each observer swapped sides and the procedure was repeated. The Boso-Mediwatch was then applied to the right wrist by observer 1 and was compared with mercury sphygmomanometry of the left upper arm by observer 2. Each observer once again swapped sides and the procedure was repeated. An identical protocol was followed for the Omron R3 in a further 20 treated hypertensive subjects and 20 normotensive subjects. 3. There were no significant differences between observers or left versus right arm for either oscillometric device or when measurements were performed by mercury sphygmomanometry. In normotensive subjects, the Boso-Mediwatch readings were higher than mercury sphygmomanometer readings, with mean differences (95% confidence intervals) of 3.9 (0.1, 7.6; P = 0.045) and 7.0 mmHg (4.7, 9.2; P < 0.001) for systolic and diastolic BP, respectively. In hypertensive subjects, the Boso-Mediwatch readings were lower for systolic BP (mean difference -6.0 mmHg (-11.6, -0.3; P = 0.04) but were higher for diastolic BP (mean difference 3.8 mmHg (1.4, 6.3; P < 0.01). 4. In normotensive subjects, the Omron R3 readings were higher, with mean differences of 3.2 (0.6, 5.8; P = 0.018) and 4.2 mmHg (1.6, 6.7; P = 0.003) for systolic and diastolic BP, respectively. In hypertensive subjects, the Omron R3 readings were lower for both systolic and diastolic BP (mean differences: -5.8 (-8.8, -2.8; P = 0.001) and -5.5 (-9.3, -1.6; P = 0.008), respectively). 5. For the Boso-Mediwatch, weighted least products analysis confirmed the presence of both fixed and proportional error for systolic BP but not for diastolic BP. For the Omron R3, fixed or proportional error was not detected for either systolic or diastolic BP. 6. These wrist oscillometric devices, although offering portability and convenience, give BP measurements that frequently differ substantially (by at least 5 mmHg) from readings simultaneously measured at the upper arm by a mercury sphygmomanometer. The magnitude and direction of differences detected are dependent on both the device used and the underlying level of BP.     

Effect of persistent use of antihypertensives on blood pressure goal attainment

ABSTRACT

Objective: Discontinuation rates with antihypertensive drugs in real life are high. The present study investigates the relationship between persistence with antihypertensive drugs (AHT) and blood pressure (BP) goal attainment in daily clinical practice.

Methods: In the PHARMO Record Linkage System, which includes drug dispensing and hospital records for >?2 million inhabitants in the Netherlands, new users of AHT ≥?18 years were identified for the period 1999–2004. Patients with elevated blood pressure (systolic BP ≥140 and/or diastolic BP ≥?90?mmHg) within 6 months prior to onset of AHT treatment and a BP measurement within 6–12 months of treatment onset were included in the study cohort. Persistent AHT use was determined by summing the number of days of continuous treatment (gap between dispensings <?30 days) from start of treatment onwards. Patients with a BP below 140/90?mmHg at the first BP measurement within 6–12?months of treatment onset were defined as having attained goal.

Results: The study included 1271 patients with a mean systolic BP of 174 ± 22?mmHg and a mean diastolic BP of 100 ± 12?mmHg. Persistent AHT use was associated with a 40% increased chance of BP goal attainment (RR_adj = 1.41; 95% CI: 1.08–1.85) after adjustment for gender, age, systolic blood pressure at start, and time to the BP measurement.

Conclusion: Persistent use of AHT leads to increased blood pressure goal attainment in daily clinical practice.     

Effectiveness of a trandolapril-based treatment regimen in subjects with isolated systolic hypertension in Canada

ABSTRACT

Objective: This report evaluates the effectiveness of a titration-based, escalating dose regimen based on trandolapril in subjects with isolated systolic hypertension (ISH) treated in Canadian clinical practice.

Methods: Substudy of the TRAIL (Trandolapril Regimen Applied In real Life) study; a prospective, open-label, single cohort, multicentre study in 192 Canadian primary care practices. Subjects with ISH received trandolapril therapy, initiated at 1?mg/day (0.5?mg/day in subjects on diuretics) and increased to 2 or 4?mg at 4 and 9 weeks, respectively, in those not achieving blood-pressure (BP) targets, subject to tolerability. If BP was not controlled after 14 weeks of treatment subjects could be put on trandolapril 4?mg/verapamil 240?mg while continuing the diuretic, or verapamil could be added to the existing regimen. The observation period was 26 weeks. The primary outcome measure was the achievement of target BP levels after 14 weeks.

Results: Systolic BP (SBP) was significantly (p?<?0.01) reduced from 167.3?±?8.7?mmHg at baseline to 136.8?±?14.0?mmHg (means?±?SD) at Week 14. The reductions were maintained at Week 26: mean SBP at this time point was 137.4?±?12.5?mmHg. The target BP levels of ≤140/90?mmHg at Week 14 was reached by 67% of subjects with ISH. Among study limitations were the observational design; the lack of randomisation and control group, and the fact that subjects with ISH represented a comparatively small number of subjects.

Conclusions: A titration-based, escalating-dose regimen based on trandolapril is effective in subjects with ISH under treatment conditions seen in general clinical practice in Canada.     

Distribution of blood pressure and prevalence of arterial hypertension in the old population of Cracow.

The aim of the present epidemiological study was to recognize the distribution of blood pressure (BP) and the prevalence of arterial hypertension (AH) in the aged (> or = 70 years) population in Cracow. The data were obtained from the studied group of 512 persons (153 men and 359 women) which corresponds to 72.4% of the randomly chosen group. The mean systolic BP was 159.7 in males and 164.3 mmHg in females (p < 0.05). Diastolic BP was 86.3 mmHg and 87.3 mmHg (n.s.), respectively. We observed the single peaked distribution of BP. According to the WHO epidemiological criteria of AH (BP > or = 160 = 95 mmHg) hypertension was found in 60.6% (49.7% M and 64.8% F) with systolic AH 32.3%, systolic+diastolic in 25.4% and diastolic AH alone in 2.9% of this group.     

Efficacy and tolerability of the perindopril/indapamide combination therapy for hypertension: the PRIMUS study

BACKGROUND: Tight blood pressure (BP) control is required to reduce cardiovascular morbidity and mortality. OBJECTIVE: To evaluate the efficacy and tolerability of the first line combination perindopril/indapamide in hypertension in daily practice. DESIGN AND METHODS: In this prospective, open-label, observational trial, 1892 general practitioners in Germany recruited patients with hypertension (n = 8023; mean age 59.6 years, 48.1% males, body mass index 27.6 kg/m2, systolic BP >or= 140 mmHg and/or diastolic BP >or= 90 mmHg) between October 2002 and December 2004. Patients received perindopril 2 mg/indapamide 0.625 mg for 12 weeks. BP measured in the general practice setting, safety, and tolerability were evaluated after 4 and 12 weeks. RESULTS: At baseline, most patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8 mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean BP 166.1/97.2 mmHg) and 58% of patients had uncontrolled BP despite preexisting antihypertensive treatment (163.5/94.9 mmHg). Previous treatment consisted of beta-blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%), diuretics (28.8%), AT-I receptor antagonists (7.1%), and other treatments (8.1%). In the entire study cohort, treatment with perindopril/indapamide significantly decreased systolic BP (27.9 mmHg), diastolic BP (13.7 mmHg), and pulse pressure (14.2 mmHg), compared with baseline (p < 0.0001); 96% of patients responded to treatment and in 50% of patients BP was normalized (< 140/90 mmHg). Treatment dose was doubled in 9.5% of patients. Similar results were found in various subgroup analyses (newly diagnosed patients, the elderly, and patients with isolated systolic hypertension, additional cardiovascular risk factors, associated diseases, or target organ damage). The most frequent adverse events (< 1% of patients) were dry cough and nausea. CONCLUSIONS: The open-label, observational study PRIMUS, extends the existing evidence that the first line combination treatment of hypertension with perindopril/indapamide is effective, safe, and well tolerated in a representative cross-section of patients with newly diagnosed or pretreated but uncontrolled hypertension in daily practice.     

The blood pressure lowering potential of sulodexide – a systematic review and meta‐analysis

AimsSulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti‐albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that sulodexide may lower blood pressure (BP). In this meta‐analysis, we therefore investigated the antihypertensive effects of sulodexide treatment.MethodsWe selected randomized controlled trials that investigated sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data.ResultsEight studies, totalling 3019 subjects (mean follow‐up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P < 0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r ²=0.83, P < 0.001) and diastolic BP (r ²=0.41, P = 0.02) reductions after sulodexide treatment. In addition, systolic (r ²=0.41, P = 0.03) and diastolic BP reductions (r ²=0.60, P = 0.005) were significantly associated with albuminuria reduction.ConclusionOur data suggest that sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of sulodexide.     

Evaluation of long-term efficacy and acceptability of indapamide SR in elderly hypertensive patients

OBJECTIVE: To assess the long-term antihypertensive efficacy and acceptability of indapamide SR 1.5 mg in elderly hypertensive patients (> or = 65 years). STUDY DESIGN: Open, 12-month, follow-up study of 444 patients, treated with indapamide SR, who were responders and/or achieved target BP levels following a 3-month, randomised, controlled, double-blind short-term comparison of indapamide SR versus hydrochlorothiazide 25 mg and amlodipine 5 mg. RESULTS: The long-term decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) after 12 months follow-up with indapamide SR was -24.0/-13.1 mmHg from baseline (M0). The percentage of patients that achieved target BP levels (DBP < 95 mmHg, SBP < or = 160 mmHg) was 80.1% [84.3% for isolated systolic hypertension (ISH) subgroup], and the response rate (BP < 140/90 mmHg or decrease in supine diastolic BP > or = 10 mmHg or in supine systolic BP > or = 20 mmHg) 81.5%. Blood pressure (BP) remained stable throughout the 12 months follow-up period (M3-M15), whatever the previous treatment received during the 3-month, doubleblind period (M0-M3). Clinical and biological acceptability was good. A low occurrence of withdrawals (7.2%), was reported. CONCLUSION: Over the course of the long-term, 12-month follow-up study, indapamide SR was shown to be an effective and well tolerated antihypertensive therapy, even after a switch from amlodipine or hydrochlorothiazide, in patients aged 65 years-80 years with systolo-diastolic hypertension (SDH) or ISH.     

Hypertension registers in general practice: levels of control and nondrug management

Sixty-five general practitioners throughout Northland agreed to establish and maintain hypertension registers for a three year trial period beginning in 1982. Opportunistic blood pressure screening was undertaken of all patients aged 20-69 attending practices for whatever reason. Patients with an average of six readings on at least three separate occasions which exceeded WHO criteria for hypertension (diastolic blood pressure greater than 95 mmHg and/or systolic blood pressure greater than 160 mmHg) were entered onto the registers as were patients already receiving antihypertensive drugs. In all 3703 patients were registered. The percentage exceeding WHO criteria fell from 49.4% to 38.8% for those followed up for twelve months and from 48.6% to 34.5% for those followed up for twenty-four months. The percentage with diastolic blood pressure less than 90 mmHg increased significantly for each follow up group and with length of follow up. Overall 8.2% at entry were managed without drugs, for those followed up for thirty months this fell to 6.2% with individual practice percentage varying from nil to over twenty. There appears scope to manage between 10-20% of hypertensives without drugs.     

Antihypertensive efficacy and safety of benidipine and its effects on cardiac structure and function in elderly Chinese patients with mild to moderate hypertension: an open-label, long-term study

Benidipine (CAS 91599-74-5) has been reported as an effective antihypertensive treatment and its cardioprotective effects have been shown in several basic and clinical studies. However, the long-term efficacy and safety of benidipine remain unknown in elderly Chinese patient with hypertension. In this prospective, multicenter, open-label clinical trial, 152 eligible patients aged 60 to 75 years with mild to moderate essential hypertension (sitting systolic blood pressure (BP) > or = 140 mmHg and/or sitting diastolic BP > or = 90 mmHg) entered a 52-week study. All patients initially received benidipine 2-4 mg once a day, followed by titration to benidipine 8 mg/day to achieve the target BP (< 140/90 mmHg in non-diabetics and <130/80 mmHg in diabetics). Add-on hydrochlorothiazide (CAS 58-93-5) and/or metoprolol tartaric acid (CAS 3750-58-6) were permitted during the study. Overall, 132 patients completed the 52-week treatment with benidipine as monotherapy or combination therapy. It showed that the regimen based on benidipine provided an obvious mean trough BP reduction of 13.8 +/- 12.4/8.3 +/- 9.2 mmHg (p < 0.001), and 62.5% of patients reached the target BP. In patients with left ventricular hypertrophy, the left ventricular mass index significantly decreased from 147.1 +/- 27.6 g/m2 at baseline to 136.0 +/- 17.5 g/m2 at 52 weeks (p = 0.036). Clinical adverse events (AEs) were found in 15.1% of all patients, and six patients discontinued the treatment due to drug-related AEs during the entire trial. Patients' compliance was an average of 98.7%. Benidipine, with a favorable tolerability profile, provides a long-term antihypertensive effect and potential benefit for the heart in elderly patients with mild to moderate hypertensive, suggesting that it is suitable for elderly patients with hypertension.     

Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study

AIMS: Aldosterone/renin ratio is an index for inappropriate aldosterone activity, and it is increasingly being used to screen for primary aldosteronism within the hypertensive population. It may also be a good index to help predict the response to spironolactone. To assess the blood pressure response to oral spironolactone in hypertensive patients with primary aldosteronism identified with raised aldosterone to renin ratio. METHODS: We conducted a prospective cohort study of hypertensive patients with raised aldosterone/renin ratio, who failed to suppress plasma aldosterone with salt loading and fludrocortisone suppression test. These patients were treated with spironolactone and were followed-up for a period of up to 3 years. RESULTS: We studied 28 (12 male) subjects with a mean age of 55 (s.d. 10) years who were followed up for a mean period of 12.9 (7) months. At baseline, the patients were taking a mean of 2.1 (1.2) antihypertensive drugs, but despite this 16/28 (57%) had diastolic BP >90 mmHg, 39% with systolic BP >160 mmHg. After commencing spironolactone, three patients complained of breast tenderness but continued treatment and one patient was intolerant of spironolactone and had to stop treatment. Of the remaining 27 patients, the mean number of antihypertensive drugs used dropped to spironolactone plus 0.7 (s.d. 0.9). All but one patient (96%) achieved a diastolic BP相似文献   

Air-conditioning and health: effect on pulse and blood pressure of young healthy Nigerians

Blood pressure and pulse of 32 young healthy Nigerian volunteers were determined after they had been in an air-conditioned room from between 60 and 90 minutes. The same determinations were made at the same time of another day with air-conditioning switched off for the same period. The mean systolic blood pressure (SBP) was 115.3 +/- 11.5 mmHg under air-conditioner (AC) and 108.5 +/- 10.1 mmHg without air-conditioning. This difference was statistically significant (p less than 001). Similarly, diastolic blood pressure (DBP) was higher in AC, 69.4 +/- 8.9 mmHg, than without AC, 66.5 +/- 9.1 mmHg (p less than 025), while mean blood pressure was also higher in AC, 84.9 +/- 9.1 mmHg, than without, 79.9 +/- 7.7 mmHg (less than 005). There was no significant different in pulse rate. These differences in the BP of normal young subjects are not thought to be of clinical significance but the result suggests that study of the effect of AC on BP and pulse in older subjects and hypertensive subjects is desirable.     

VOLUNTARY BLOOD PRESSURE CONTROL USING CONTINUOUS SYSTOLIC BLOOD PRESSURE BIOFEEDBACK

1. Ability to alter blood pressure (BP) acutely with continuous systolic (SBP) BP biofeedback was assessed in volunteers using a new non-invasive finger BP monitor. 2. Reliability of finger BP measurement was demonstrated in six hypertensive subjects (21-60 years), by beat-to-beat comparison with brachial intra-arterial BP over 90 min. Wide variation of BP was achieved by physiological manoeuvres. Mean error of finger BP was -3.0/-2.2 mmHg with intra-subject s.d. of 7.2/5.4 mmHg. 3. Thirteen normotensives (21-51 years) were paid to undergo 30 trials of SBP biofeedback in six sessions over 3 weeks. The SBP trend was displayed on a monitor with appropriately 'shaped' targets; each trial consisted of BP-raising and -lowering periods of 45 and 90 s respectively with intervening 45 s baselines. 4. Nine subjects raised BP, on analysis of the last 10 trials, by an average of 18.8 mmHg while five of the 13 successfully lowered BP by an average of 10.0 mmHg. BP lowering was best achieved by diminishing respiratory rate and depth, and muscular relaxation. 5. Demonstration of large BP reductions in five of 13 normotensives using strategies applicable to longer training sessions warrants further investigations in hypertensive subjects, focusing on mediating mechanisms and transfer of effect beyond the laboratory.     

Pharmacogenetics of drug-induced arrhythmias: a feasibility study using spontaneous adverse drug reactions reporting data

PURPOSE: The bottleneck in pharmacogenetic research on rare adverse drug reactions (ADR) is retrieval of patients. Spontaneous reports of ADRs may form a useful source of patients. We investigated the feasibility of a pharmacogenetic study, in which cases were selected from the database of a spontaneous reporting system for ADRs, using drug-induced arrhythmias as an example. METHODS: Reports of drug-induced arrhythmias to proarrhythmic drugs were selected from the database of the Netherlands Pharmacovigilance Centre (1996-2003). Information on the patient's general practitioner (GP) was obtained from the original report, or from another health care provider who reported the event. GPs were contacted and asked to recruit the patient as well as two age, gender and drug matched controls. Patients were asked to fill a questionnaire and provide a buccal swab DNA sample through the mail. DNA samples were screened for 10 missense mutations in 5 genes associated with the congenital long-QT (LQT) syndrome (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2). RESULTS: We identified 45 eligible cases, 29 GPs could be contacted of which seven were willing to participate. Four cases and five matched controls could be included in the study, giving an overall participation rate of 9% (4/45). The main reason for GPs not being willing to participate was lack of time. Variants were identified in KCNH2, SCN5A and KCNE1. CONCLUSIONS: Spontaneous reporting systems for ADRs may be used for pharmacogenetic research. The methods described, however, need to be improved to increase participation and international collaboration may be required.     

胰高血糖素肽1对糖尿病伴高血压患者血压变异性的影响

【摘要】目的 探讨胰高血糖素肽1（GLP-1）对2型糖尿病伴高血压患者血压变异性（BPV）的影响。方法 选取糖尿病伴高血压患者120例,使用GLP-1对其进行治疗,检测患者使用前及使用6个月后体质指数（BMI）、空腹血糖、糖化血红蛋白、血清肌酐、血脂等,并进行24h动态血压监测,得到短时BPV。比较治疗前后的相关指标。结果 使用GLP-1后6个月,患者空腹血糖（mmol/L :7.12±0.64vs9.19±2.78）、糖化血红蛋白（%:7.00±0.14vs8.28±1.32）、BMI（kg/m2: 19.30±3.24vs24.50±4.53）较治疗前下降（P<0.05）,达到控制目标。24h收缩压（mmHg :135.02±16.57vs139.52±15.60）、白昼收缩压（mmHg:132.50±14.60vs136.44±14.24）、24h收缩压变异性（mmHg:12.20±1.44vs12.73±1.66）、白昼收缩压变异性（mmHg:11.11±1.48vs11.74±1.52）、白昼舒张压变异性（mmHg:7.03±1.42vs7.43±1.45）也降低（P<0.05）。结论 GLP-1可降低糖尿病伴高血压患者的BPV。