Screening for Primary Aldosteronism in a Population of Patients With Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,183
- 试验地点
- 1
- 主要终点
- Prevalence estimates of primary aldosteronism (PA) and of PA subtypes in a Swedish population of primary care patients with arterial hypertension
研究概览
简要总结
Primary aldosteronism (PA) is an under-diagnosed cause of arterial hypertension. Cardiovascular morbidity and mortality in hypertension rises significantly for patients who have aldosterone overproduction when compared with those with primary hypertension and the same level of blod pressure elevation. The classical signs of PA such as severe hypertension and hypokalemia may be absent, why screening in defined risk groups has been recommended. Screening has not been systematically implemented in Sweden, probably due to expensive, time and effort-consuming clinical routine protocols and low awareness of the problem among clinicians. The prevalence of PA in patients with hypertension in Sweden has not been studied adequately, and few studies from Northern Europe have addressed the problem.
The primary objective is to investigate prevalence of PA among patients with hypertension in primary care and to implement and assess optimal treatment. Discovered cases of PA will go through routine clinical work-up in order to distinguish the subtype of PA, which includes computed tomography of adrenals and adrenal vein sampling (AVS) in those willing and fit for surgical treatment. Treatment will be then chosen depending on the PA subtype. Those with unilateral disease who are willing and fit for surgery will be offered unilateral minimally invasive adrenalectomy. Patients who oppose or have contraindications to operative treatment, as well as patients with bilateral disease will be offered medical treatment with mineralocorticoid receptor antagonists (MRA).
Study participants will be then followed up one year after surgery or initiation of specific medical treatment. Please se outcome measures for relevant description of those.
Blood samples will be collected from patients with confirmed PA to be stored in a biobank for potential future genetical and biochemical studies. A subgroup of patients with PA will undergo adrenal-specific positron-emission tomography to assess the possibility to un-invasively diagnose and subtype PA.
详细描述
Primary care hypertensive patients corresponding to eligibility criteria will be contacted by letter (including informed consent form) and thus invited to take part in the present study. On the one hand, the letter will be sent to a group of hypertensive patients who could be identified from the hypertension diagnosis based search through the database belonging to the computerized patient journal system. On the other hand, the letter will be offered to consecutive hypertension patients who contact their primary care facility for whatever reason. The first 1200 patients who have given informed consent to participation are going to be enrolled in the study.
The study will be conducted mostly in Karlstad, a town in central Sweden with population of about 89000 people. Some of approximately 4000 hypertensive patients enlisted at one of the major primary care facilities in town, Gripen Outpatient Clinic, will be contacted in the above manner. Gripen serves totally about 21000 outpatients. If needed for enrollment purposes, one other of the regions major outpatient clinics will be involved. Aldosterone - Renin Ratio (ARR), intravenous sodium chloride (i.v. NaCl) suppression test and adrenal computed tomography (CT) will de done at Karlstad Central Hospital - at Surgical, Endocrinological and X-ray Departments, respectively. AVS is planned to be carried out at an X-ray laboratory at Uppsala University Hospital. Adrenalectomies will be performed at Surgical departments in both Uppsala and Karlstad.
After a two week run-in period with liberal salt intake and abstinence form licorice and chewing tobacco, blood samples will be taken from study participants. Sampling will be performed at 8-10 a.m., ideally 2 hrs after awakening and after 5-15 min of seated rest.
Plasma aldosterone, plasma renin (Direct Renin Concentration, DRC), serum sodium, potassium and creatinine are going to be analysed. Aldosterone-Renin Ratio (ARR) > = 50 pmol/mU and plasma aldosterone > = 170 pmol/l are the criteria that will prompt further work-up upon suspicion of PA. Patients with other test results will be considered to not have PA - if they are normokalemic and not using mineralocorticoid receptor antagonists (MRA).
Patients using MRA will be offered optimization and retest. MRA will be then discontinued for at least 6 weeks and substituted if needed with alfa- or calcium blockers. Hypokalemic patients with test results not prompting suspicion of PA will also be optimized with potassium supplementation until normokalemia is sustained before retesting.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •participants must have Swedish personal number (that gives right to all kinds of necessary planned health care)
排除标准
- •pregnancy
结局指标
主要结局
Prevalence estimates of primary aldosteronism (PA) and of PA subtypes in a Swedish population of primary care patients with arterial hypertension
时间窗: For each patient, the time necessary to go through initial (sometimes repeated) screening with ARR, then (sometimes repeated) confirmation testing with i.v. NaCl-suppression test will be approximately 6 months
ARR - Aldosterone-Renin Ratio; i.v. - intravenous; NaCl - sodium chloride;
次要结局
- Occurrence of any surgical complications.(Early complications are recorded during postoperative hospital stay, approximately 1 year after first screening. Late ones are recorded at the one year postoperative follow-up patient contact, approximately 2 years after first screening.)
- Changes in clinical characteristics of hypertension and in antihypertensive treatment regimen still needed - one year after the diagnosis of primary aldosteronism had been stated and specific treatment applied.(Evaluation of treatment effects is done at the follow-up patient contact one year after adrenal surgery or initiation of specific medical treatment - approximately 1,5 - 2 years after the first screening.)
- Serum potassium level - one year after the diagnosis of primary aldosteronism had been stated and specific treatment applied.(Evaluation is done at the follow-up patient contact one year after adrenal surgery or initiation of specific medical treatment - approximately 1,5 - 2 years after the first screening.)
- Any potassium supplementation if still needed - one year after the diagnosis of primary aldosteronism.(Evaluation is done at the follow-up patient contact one year after adrenal surgery or initiation of specific medical treatment - approximately 1,5 - 2 years after the first screening.)
- Serum creatinine - one year after the diagnosis of primary aldosteronism.(Evaluation is done at the follow-up patient contact one year after adrenal surgery or initiation of specific medical treatment - approximately 1,5 - 2 years after the first screening.)
- Frequency of conversion from planned laparoscopic adrenalectomy to an open procedure.(Recorded during postoperative hospital stay, approximately 1 year after first screening.)
- Postoperative pain characteristics.(Early postoperative pain scores are recorded during postoperative hospital stay, approximately 1 year after first screening. Late ones are recorded at the one year postoperative follow-up patient contact, approximately 2 years after first screening.)
- Time before return to work after adrenalectomy.(Recorded as soon as the patient goes back to work after the operation - latest at one year postoperative follow-up patient contact, approximately 2 years after first screening.)
- Occurrence of any complications related to Adrenal Vein Sampling (AVS).(Early complications are recorded during and on the day after the procedure. Late ones are recorded at the one year follow-up patient contact, approximately 2 years after first screening.)
- The proportion of screening-discovered patients with PA who could be offered surgical treatment - and who have accepted operation and have been unilaterally adrenalectomized.(Considering work-up time and waiting time for planned surgery of this type it is realistic to assume minimal time frame of approximately 2 years)
- Control of Aldosterone Renin Ratio (ARR) after the same 2 weeks long preliminary optimization period as at initial ARR screening - one year after surgical treatment for PA.(Evaluation is done at the follow-up patient contact one year after adrenal surgery - approximately 2 years after the first screening.)
- Duration of hospital stay after adrenalectomy.(Recorded during postoperative hospital stay, approximately 1 year after first screening.)
研究者
Per Hellman
Professor, Head of the Department of Surgical Sciences, Uppsala University
Uppsala University