Morbidity and mortality risk among patients with screening-detected severe hypertension in the Malmö Preventive Project.

OBJECTIVE: Screening of hypertension has been advocated for early detection and treatment. Severe hypertension (grade 3 hypertension) is a strong predictor for cardiovascular disease. This study aimed to evaluate not only the risk factors for developing severe hypertension, but also the prospective morbidity and mortality risk associated with severe hypertension in a population-based screening and intervention programme. RESEARCH DESIGN AND METHODS: In all, 18,200 individuals from a population-based cohort underwent a baseline examination in 1972-1992 and were re-examined in 2002-2006 in Malmö, Sweden. In total, 300 (1.6%) patients with severe hypertension were identified at re-examination, and predictive risk factors from baseline were calculated. Total and cause-specific morbidity and mortality were followed in national registers in all severe hypertension patients, as well as in age and sex-matched normotensive controls. Cox analyses for hazard ratios were used. RESULTS: Men developing severe hypertension differed from matched controls in baseline variables associated with the metabolic syndrome, as well as paternal history of hypertension (P < 0.001). Women with later severe hypertension were characterized by elevated BMI and a positive maternal history for hypertension at baseline. The risk of mortality, coronary events, stroke and diabetes during follow-up was higher among severe hypertension patients compared to controls. For coronary events, the risk remained elevated adjusted for other risk factors [hazard ratio 2.31, 95% confidence interval (CI) 1.22-4.40, P = 0.011]. CONCLUSION: Family history and variables associated with metabolic syndrome are predictors for severe hypertension after a long-term follow-up. Severe hypertension is associated with increased mortality, cardiovascular morbidity and incident diabetes in spite of treatment. This calls for improved risk factor control in patients with severe hypertension.

Family history as a predictor of hospitalization for hypertension in Sweden.

OBJECTIVE: Hypertension clusters in families. However, no nationwide study has investigated the family history as a predictor of hospitalization for hypertension, which was the purpose of this study. RESEARCH DESIGN AND METHODS: The study is a nationwide follow-up study. Swedish Multigeneration Register data for individuals aged 0-76 years were linked to Hospital Discharge Register data for 1964-2008. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized with a main diagnosis of hypertension compared with those whose relatives were not. RESULTS: The total number of patients hospitalized with hypertension was 37,686. The familial SIR was 2.18 for individuals with one affected sibling, 44.83 for individuals with two affected siblings and 57.18 for individuals with three or more affected siblings. The SIR was 1.95 for parents with one affected child, 3.73 for parents with two affected children and 9.22 for parents with three or more affected children. The familial SIR among offspring was 1.84 for those with one affected parent and 3.62 for those with two affected parents. The familial risk for hospitalization with hypertension among offspring aged less than 30 years was 2.50 and 1.57 in those aged more than 60 years. Familial risks were similar for men and women. Spouses had low overall familial risks (SIR=1.2). CONCLUSION: Hospitalization for hypertension clusters in families. Very high risks were observed in families with multiple affected siblings, though the parent-offspring transmission was lower, suggesting the segregation of recessive or interacting susceptibility genes. The low familial risk in spouses suggests a minor nongenetic contribution.

Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area.

OBJECTIVE: To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. DESIGN: Patient survey study. SETTING AND SUBJECTS: A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. MAIN OUTCOME MEASURES: ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). RESULTS: Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. CONCLUSION: Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted.

Captopril suppression: limitations for confirmation of primary aldosteronism.

INTRODUCTION: The aldosterone/renin ratio (ARR) is the first line screening test for primary aldosteronism (PA). However, in hypertensive patients with an increased ARR, PA needs to be confirmed by other means. METHODS: A 25 mg oral captopril test was performed in 16 healthy subjects to obtain reference values for aldosterone and ARR at 120 minutes after the test. Subsequently these data were applied to 46 hypertensive patients screened for PA with an increased ARR. RESULTS: At 120 minutes after the captopril test ARR decreased in healthy subjects within a narrow range, but remained high in patients with PA and in patients with primary hypertension, especially for those with low renin characteristics. At 120 minutes after captopril, the range of ARR in primary hypertensive patients overlapped in 88% of the cases with the range of the ARR in the PA patients. Sensitivity and specificity of basal ARR and ARR after the captopril test to diagnose PA, calculated as receiver operator characteristics, showed an area under the curve of 0.595 for basal ARR and 0.664 for ARR at 120 minutes after the test. CONCLUSION: The ARR at 120 minutes after the captopril test is only marginally better than basal ARR in diagnosing PA in hypertensive patients screened with an increased ARR. Owing to an overall limited capacity to clearly discriminate PA from primary hypertension, the test could not therefore be recommended for the confirmatory diagnosis of PA.

Re-evaluation of the fludrocortisone test: duration, NaCl supplementation and cut-off limits for aldosterone.

OBJECTIVE: Primary aldosteronism (PA) is the most common form of secondary hypertension. Thus, the aims of this study were: (1) to clarify whether the fludrocortisone suppression test (FST), which confirms autonomous aldosterone secretion, is reliable when carried out during a shorter period of time and (2) to confirm the importance of NaCl supplementation. The cut-off limits already obtained for aldosterone in healthy subjects during the FST were applied in hypertensive patients with a high aldosterone to renin ratio (ARR). MATERIAL AND METHODS: The healthy subjects were allocated to three groups. Fludrocortisone was administered 4 times daily over 4 days and sodium chloride was supplemented in 3 different doses. The result was applied in 24 hypertensive patients, in 24 healthy subjects (10 women (23-38 years old) and 14 men (23-58 years old)) and in 24 patients with hypertension and high ARR (16 women (45-74 years old) and 8 men (56-73 years old)). Blood pressure, aldosterone, renin, potassium and sodium were measured. RESULTS: After three days of FST, there was a significant decrease in the serum level of aldosterone in the healthy subjects, regardless of high or low sodium chloride supplementation (p<0.001). The decrease in serum aldosterone was significantly less pronounced in patients with PA than in healthy subjects and hypertensive patients without PA (p<0.001). The 95th percentile of plasma aldosterone at the end of the test was 225 pmol/L. CONCLUSIONS: The FST can be shortened to 3 days and a daily 500 mg NaCl supplementation is sufficient. A cut-off value for aldosterone of 225 pmol/L after 4 days with FST is appropriate.

High frequency of primary hyperaldosteronism among hypertensive patients from a primary care area in Sweden.

OBJECTIVE: To search for primary hyperaldosteronism (PHA) among previously known hypertensive patients in primary care, using the aldosterone/renin ratio (ARR), and to evaluate clinical and biochemical characteristics in patients with high or normal ratio. DESIGN: Patient survey study. SETTING AND SUBJECTS: The study population was recruited by written invitation among hypertensive patients in two primary care areas in Sweden. A total of 200 patients met the criteria and were included in the study. MAIN OUTCOME MEASURES: The ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was set to 100, as confirmed in 28 healthy subjects. Patients with increased ARR were considered for a confirmatory test, using the fludrocortisone suppression test. RESULTS: Of 200 patients, 50 patients had ARR > 100; 26 patients were further evaluated by fludrocortisone suppression test. Seventeen of these patients had an incomplete aldosterone inhibition. CONCLUSION: In total 17 of 200 evaluated patients (8.5%) had an incomplete suppression with fludrocortisone. This confirms previous reports on a high frequency of PHA. No significant biochemical or clinical differences were found among hypertensive patients with PHA compared with the whole sample.