Implementation of shared decision making by physician training to optimise hypertension treatment. Study protocol of a cluster-RCT

ABSTRACT: BACKGROUND: Hypertension is one of the key factors causing cardiovascular diseases which make up the most frequent cause of death in industrialised nations. However about 60% of hypertensive patients in Germany treated with antihypertensives do not reach the recommended target blood pressure. The involvement of patients in medical decision making fulfils not only an ethical imperative but, furthermore, has the potential of higher treatment success. One concept to enhance the active role of patients is shared decision making. Until now there exists little information on the effects of shared decision making trainings for general practitioners on patient participation and on lowering blood pressure in hypertensive patients. METHODS: In a cluster-randomised controlled trial 1800 patients receiving antihypertensives will be screened with 24 h ambulatory blood pressure monitoring in their general practitioners' practices. Only patients who have not reached their blood pressure target (approximately 1200) will remain in the study (T1 -- T3). General practitioners of the intervention group will take part in a shared decision making-training after baseline assessment (T0). General practitioners of the control group will treat their patients as usual. Primary endpoints are change of systolic blood pressure and change of patients' perceived participation. Secondary endpoints are changes of diastolic blood pressure, knowledge, medical adherence and cardiovascular risk. Data analysis will be performed with mixed effects models. DISCUSSION: The hypothesis underlying this study is that shared decision making, realised by a shared decision making training for general practitioners, activates patients, facilitates patients' empowerment and contributes to a better hypertension control. This study is the first one that tests this hypothesis with a (cluster-) randomised trial and a large sample size.Trial registrationWHO International Clinical Trials: http://apps.who.int/trialsearch/Trial.aspx?TrialID=DRKS00000125.     

Overweight,Obesity, and Blood Pressure: The Effects of Modest Weight Reduction

Several large epidemiological studies have shown an association between body mass index and blood pressure in normal weight and overweight patients. Weight gain in adult life especially seems to be an important risk factor for the development of hypertension. Weight loss has been recommended for the obese hypertensive patient and has been shown to be the most effective nonpharmacological treatment approach. However, long‐term results of weight loss programs are disappointing with people often regaining most of the weight initially lost. In recent years, a modest weight loss, defined as a weight loss of 5% to 10% of baseline weight, has received increasing attention as a new treatment strategy for overweight and obese patients. A more gradual and moderate weight loss is more likely to be maintained over a longer period of time. Several studies have confirmed the blood pressure‐lowering effect of a modest weight loss in both hypertensive and nonhypertensive patients. A modest weight loss can normalize blood pressure levels even without reaching ideal weight. In patients taking antihypertensive medication, a modest weight loss has been shown to lower or even discontinue the need for antihypertensive medication. In patients with high normal blood pressure, a modest weight loss can prevent the onset of frank hypertension. The blood pressure‐lowering effect of weight loss is most likely a result of an improvement in insulin sensitivity and a decrease in sympathetic nervous system activity and occurs independent of salt restriction. In conclusion, a modest weight loss that can be maintained over a longer period of time is a valuable treatment goal in hypertensive patients.     

Accurate,reproducible measurement of blood pressure.

The diagnosis of mild hypertension and the treatment of hypertension require accurate measurement of blood pressure. Blood pressure readings are altered by various factors that influence the patient, the techniques used and the accuracy of the sphygmomanometer. The variability of readings can be reduced if informed patients prepare in advance by emptying their bladder and bowel, by avoiding over-the-counter vasoactive drugs the day of measurement and by avoiding exposure to cold, caffeine consumption, smoking and physical exertion within half an hour before measurement. The use of standardized techniques to measure blood pressure will help to avoid large systematic errors. Poor technique can account for differences in readings of more than 15 mm Hg and ultimately misdiagnosis. Most of the recommended procedures are simple and, when routinely incorporated into clinical practice, require little additional time. The equipment must be appropriate and in good condition. Physicians should have a suitable selection of cuff sizes readily available; the use of the correct cuff size is essential to minimize systematic errors in blood pressure measurement. Semiannual calibration of aneroid sphygmomanometers and annual inspection of mercury sphygmomanometers and blood pressure cuffs are recommended. We review the methods recommended for measuring blood pressure and discuss the factors known to produce large differences in blood pressure readings.     

Essential hypertension and pregnancy.

Approximately 1% of pregnancies are complicated by essential hypertension. During pregnancy the blood pressure often stabilizes or improves. In patients with sustained hypertension, prospective controlled studies have demonstrated enhanced fetal survival when the blood pressure was controlled with antihypertensive medication. Such medication must be chosen carefully to avoid fetal and mateerial toxicity, and diuretics and salt restriction during pregnancy should be avoided. Among patients with essential hypertension the problem accelerates late in pregnancy in 2% to 11%; the acceleration may be predicted by determination of maternal mean arterial pressures and intravascular volumes early in pregnancy. The treatment of accelerated hypertension is identical to that of severe pre-eclampsia. Fetal loss is considerable but can be lessened by careful fetal and maternal monitoring and early controlled delivery. The risks of pregnancy in most patients with essential hypertension are small, and essential hypertension is not a uniform contraindication to pregnancy.     

Ethnic variations in the pharmacological and nonpharmacological treatment of hypertension: biopsychosocial perspective.

Blood pressure regulation is a complex, dynamic process influenced by psychosocial, behavioral, and cultural factors. Integrative theories of cross-population differences in the prevalence of hypertension and response to treatment include physiological, social, and genetic perspectives. Ethnic differences in salt sensitivity, calcium regulation of sodium flux, vascular reactivity to psychosocial stress, and drug metabolism are integral components of observed cross-cultural variations in hypertension. In general, pharmacological treatment of hypertension in blacks is most consistently achieved through diuretics and calcium-channel blockers; angiotensin-converting enzyme inhibitors and beta-blockers are more efficacious in whites. These stereotypical patterns are consistent with the higher prevalence of salt sensitivity, stress-induced vasoconstriction and slower natriuresis, and alpha-adrenergic receptor mediated vascular reactivity observed in blacks compared with whites. Some antihypertensive agents produce adverse glucose metabolic side effects, thus contraindicating their use in individuals with high sympathetic tone, insulin resistance, or obesity. Cross-population differences in adopted guidelines for treating hypertension exist but are not likely a factor in observed ethnic differences in rate of treatment or control. Attitudes toward nontraditional treatment options (e.g., herbal medicine), political and individual responsibilities in health care, and adaptations to acculturation and urbanization stress differ between and within societies and thus play a role in observed cross-cultural differences in hypertension as well. The value of regular exercise in controlling hypertension is widely recognized, and reductions in blood pressure reactivity to behavioral stress following acute exercise have been documented; however, empirical studies of ethnic differences in exercise-related blood pressure control are lacking. Overall, increased awareness of the multifactorial nature of hypertension by both the physician and the patient will facilitate treatment of this disease on an individual basis.     

Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme.

Captopril, a specific oral inhibitor of angiotensin-converting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may maintain blood pressure in essential hypertension. This does not necessarily imply that the renin-angiotensin system is the cause of the high blood pressure.     

Captopril in essential hypertension; contrasting effects of adding hydrochlorothiazide or propranolol.

Twenty-four patients with moderate to severe hypertension were treated for four weeks with captopril, an oral inhibitor of angiotensin-converting enzyme. The fall in blood pressure with captopril alone correlated with pretreatment plasma renin activity. The effect of adding either hydrochlorothiazide or propranolol to the captopril treatment was then studied. The addition of hydrochlorothiazide to captopril produced a dose-dependent fall in blood pressure. At the higher dose of the diuretic this fall in blood pressure correlated with weight loss, suggesting that when the diuretic-induced compensatory rise in angiotensin II is prevented by captopril the fall in blood pressure becomes dependent on loss of sodium and water. In contrast, the addition of propranolol to captopril produced no further fall in blood pressure, suggesting that inhibition of angiotensin-converting enzyme prevents the blood pressure lowering effect of propranolol. This may have implications for the mechanism whereby beta-blockers alone lower blood pressure. These contrasting effects of hydrochlorothiazide and propranolol in the presence of captopril indicate that in patients whose hypertension is not controlled by captopril alone the addition of increasing doses of diuretic is likely to control the blood pressure. The addition of a beta-blocker, however, is less likely to be effective.     

Malignant hypertension in women of childbearing age and its relation to the contraceptive pill.

Eleven of 34 women aged 15-44 with malignant phase hypertension were taking oral contraceptives at presentation. All had had normal blood pressure before starting to take the pill. In four the interval between the start of oral contraception and the diagnosis of malignant hypertension was less than four months, and in eight no other cause for the hypertension was found. Underlying renal disease and renal failure were less common among pill users than among non-users with malignant hypertension who were of similar age. No pill user became normotensive after withdrawal of the pill, but blood pressure was well controlled (diastolic less than 90 mm Hg) in three patients taking only one drug. By contrast, all 23 non-users needed two or more antihypertensive drugs to control blood pressure. Ten year survival was 90% among pill users and 50% among non-users. These results suggest that oral contraceptives may be a common cause of malignant hypertension in women of child-bearing age. If the pill is stopped and underlying renal disease excluded the long term prognosis for such patients is excellent.     

Randomised,double blind,multicentre comparison of hydrochlorothiazide,atenolol, nitrendipine,and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.

OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME MEASURES: Blood pressure by means of an automatic device with repeated measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers.     

Divergent views of hospital staff on detecting and managing hypertension.

A questionnaire about detecting and managing hypertension was answered by 76 out of 110 (69%) doctors and 116 out of 195 (63%) qualified nurses in a large hospital. There was no general agreement on the method of taking diastolic blood pressures or on the level of hypertension requiring treatment. Most of the clinicians treated mild hypertension, although no proof exists that such treatment is beneficial. Almost everyone questioned agreed that measuring blood pressure in all patients attending hospital is important. Agreement should be reached, however, on which phase of diastolic blood pressure should be used.     

Nocturnal blood pressure in normotensive subjects and those with white coat,primary, and secondary hypertension.

OBJECTIVE--To compare the mean nocturnal blood pressure of patients with various forms of renal and endocrine hypertension with that in patients with primary and white coat hypertension, and normal blood pressure. DESIGN--Ambulatory monitoring of blood pressure over 24 hours in a prospective study. SETTING--Two German centres for outpatients with hypertension and kidney diseases. SUBJECTS--176 normotensive subjects, 490 patients with primary hypertension including mild and severe forms, 42 with white coat hypertension, 208 patients with renal and renovascular hypertension, 43 with hypertension and endocrine disorders, and three with coarctation of the aorta. MAIN OUTCOME MEASURES--Fall in nocturnal blood pressure. RESULTS--Blood pressure in normotensive subjects fell by a mean of 14 mm Hg (11%) systolic and 13 mm Hg (17%) diastolic overnight (2200 to 0600). The falls in patients with primary and white coat hypertension were not significantly different. In all patients with renal and renovascular hypertension, however, the fall was significantly reduced (range of fall from 3/3 mm Hg to 7/9 mm Hg). In patients with hypertension and endocrine disorders the pattern of night time blood pressure was not uniform: patients with hyperthyroidism, primary hyperaldosteronism, and Cushing''s syndrome had significantly smaller reductions in blood pressure (6/8, 4/7, 3/6 mm Hg, respectively). In patients with phaeochromocytoma the mean night time blood pressure increased by 4/2 mm Hg. In patients with hypertension, primary hyperparathyroidism, and unoperated coarctation of the aorta the falls in blood pressure were normal. CONCLUSIONS--In normotensive subjects and those with primary hypertension there is usually a reduction in blood pressure at night. In all renal forms of secondary hypertension and in most endocrine forms the reduction in blood pressure is only a third to a half of normal. Patients with primary hyperparathyroidism and unoperated coarctation of the aorta show a normal reduction.     

Vascular smooth muscle G(q) signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension

More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved.     

Endocrine disorders of sodium regulation. Role of adrenal steroids in genetic defects causing sodium loss or sodium retention

Salt and water homoeostasis is tightly regulated by a variety of control mechanisms with the adrenal steroid hormone aldosterone playing a central role. Defects or disturbances in these systems lead to either salt loss, which is life threatening in the neonatal period, or sodium retention causing hypertension. Rapid and accurate diagnosis is required to avoid severe complications. During the last few years molecular genetic advances have been identified as the basic genetic defects for a number of clinical syndromes. This knowledge has considerably increased our understanding of the basic pathways involved in sodium and water homoeostasis and of the pathophysiology of these syndromes, particularly the hypertension. In this review we have summarized the biochemical, physiological and genetic basis for clinical syndromes presenting with salt loss and failure to thrive as well as the rare but important genetic syndromes causing sodium retention and hypertension. Early diagnosis and identification will help to prevent severe complications, but it has to be emphasized that the complicated cascade of aldosterone action is still relatively poorly understood. Further syndromes may exist which once identified will help to better understand the basic physiology of aldosterone action.     

Factors predictive of attendance at clinic and blood pressure control in hypertensive patients.

Poor compliance with appointments and drug treatment is one of the recognised factors preventing effective management of hypertension. Factors predictive of poor attendance and inadequate blood pressure control in patients attending a hypertension clinic were therefore determined using univariate analyses and a multivariate logistic model. Out of 1346 patients with blood pressure exceeding 160/95 mm Hg followed up for three years, 209 (15.5%) dropped out during the first year. Variables that were significantly related to increased drop out rates were male sex, young age, obesity at entry, cigarette smoking, direct referral to the clinic as a result of screening instead of referral by a general practitioner, absence of pre-existing antihypertensive treatment at the first visit, moderate hypertension, and low socioeconomic category. Variables at entry that were significantly related to poor blood pressure control at one year were old age, evidence of coronary heart disease, severe hypertension, and raised blood glucose concentrations. Early detection of patients at high risk of drop out or poor blood pressure control might improve treatment of hypertension and allow management to be more individually adapted to each patient.     

Contribution of inappropriate treatment for hypertension to pathogenesis of stroke in the elderly.

One hundred and seventy eight patients admitted to hospital with acute cerebral infarction or transient ischaemic attack were studied to determine if their treatment had been changed during the previous three weeks and to compare their blood pressure after the stroke with premorbid values. Blood pressure measurements taken within one year before the stroke were available for 100 patients; seven of these had had a recent change in antihypertensive or diuretic treatment. Of these, three patients who had started taking frusemide because of hypertension and one whose dosage of a reserpine combination drug had been increased experienced an appreciable decrease in blood pressure immediately after the stroke; they also showed signs of haemoconcentration. The change in treatment probably contributed to the stroke in these four patients. The other three showed a smaller decrease or even an increase in blood pressure and no signs of haemoconcentration; the relation between the change in treatment and stroke is less likely in these patients. The use of high ceiling diuretics such as frusemide in the treatment of hypertension may induce hypovolaemia and hypotension, resulting in cerebral ischaemia, and are therefore best avoided in such treatment.     

The dilemma of isolated systolic hypertension.

Isolated systolic hypertension, characterized by elevated systolic blood pressure (greater than 150 to 165 mm Hg), normal diastolic blood pressure (less than 90 to 95 mm Hg) and, often, atherosclerosis, is now recognized as an important risk factor for cardiovascular disease. When the systolic pressure is 200 mm Hg or greater, or when it is 180 mm Hg or greater and accompanied by target organ damage, therapeutic intervention may be of value in patients under the age of 80 years. Low doses of thiazide diuretics have been shown to be safe and effective in lowering the systolic pressure. If the blood pressure remains high, treatment with methyldopa may be added.     

Effects of treatment for hypertension on cerebral haemorrhage and infarction.

One hundred and sixty nine patients admitted to hospital for stroke over 30 months were examined to see whether treating hypertension had influenced the incidence of cerebral haemorrhage and infarction. Seventy eight (46%) of them had normal blood pressure, 47 (28%) previously diagnosed hypertension for which they were receiving treatment, and 44 (26%) previously undiagnosed and untreated hypertension. Haemorrhagic stroke was commoner among patients with untreated hypertension, whereas infarction was commoner in patients with treated hypertension. Infarction and haemorrhage were equally prevalent in patients with normal blood pressure. Effective treatment in this population seemed to have had a substantially different impact on vascular disease, giving rise to cerebral haemorrhage as opposed to infarction. This is consistent with evidence from other studies that treatment for hypertension has little or no effect on the progression of atheroma.     

Decision to treat mild hypertension after assessment by ambulatory monitoring and World Health Organisation recommendations.

OBJECTIVE--To determine if one ambulatory blood pressure recording over 12 hours could detect those patients with mild hypertension who needed treatment according to the World Health Organisation-International Society of Hypertension (ISH) guidelines based on the causal measurement of diastolic blood pressure at successive visits to a clinic. DESIGN--Comparison of decision to treat based on one ambulatory measurement over 12 hours and standard blood pressure measurements over six months in the same patients. SETTING--Outpatient hypertension clinic. SUBJECTS--130 men and women with diastolic blood pressure of 90-104 mm Hg at second visit to clinic. MAIN OUTCOME MEASURES--Blood pressure measurements over six months. Measurement from ambulatory monitoring. Decision to treat. RESULTS--Of the 130 patients included, 108 were followed up over the six months. Treatment was started according to WHO-ISH criteria in 44 (13 at the third visit, 13 at the fourth, 18 at the fifth). According to the selected criteria for ambulatory blood pressure monitoring 41 patients would have been treated. Both methods agreed that the same 27 patients required treatment and the same 50 did not, but they did not agree in 31 patients. When calculated at the optimal diastolic blood pressure threshold determined by a receiver operating characteristic curve, the sensitivity, specificity, and positive predictive value of ambulatory blood pressure monitoring were 71% (95% confidence interval 57% to 84%), 82% (72% to 92%), and 66% (51% to 81%), respectively. CONCLUSION--If the WHO-ISH criteria are accepted as the standard for deciding to treat patients with mild hypertension the predictive value of one ambulatory blood pressure recording over 12 hours is too low to detect with confidence those patients who need treatment when managed according to these criteria.     

Relationship Between Hyperuricemia and Chronic Kidney Disease

Because approximately 70% of uric acid is excreted from the kidney, hyperuricemia occurs when renal function deteriorates. Until now, it has not been clear if the hyperuricemia seen in such renal diseases plays a role in the progression of renal disease. However, recent clinical studies show that the serum uric acid value is closely associated with hypertension in hyperuricemic patients (cross-sectional study), and also with the onset of hypertension (longitudinal study). Furthermore, one interesting report shows that treatment of hyperuricemia with allopurinol lowers blood pressure in juvenile essential hypertension patients with hyperuricemia. In addition, it is well known that hyperuricemia is closely associated with chronic kidney disease (CKD), is a risk factor for renal insufficiency in general populations, and is a poor prognostic factor of renal function in patients who also have IgA nephropathy. On the other hand, in intervention studies on hyperuricemia, the treatment of hyperuricemia with allopurinol in CKD has resulted in a fall in blood pressure and inhibition of the progression of renal damage. Conversely, the cessation of allopurinol treatment in CKD was followed by a rise in blood pressure and the development of renal damage. Furthermore, the rise of blood pressure and development of renal damage following cessation of allopurinol treatment are only seen in patients not receiving angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). This suggests that the renin angiotensin (RA) system plays an important role in the development of hypertension and renal damage from hyperuricemia.     

Randomised trial of treatment of hypertension in elderly patients in primary care.

A randomised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years. The principal antihypertensive agents were atenolol and bendrofluazide. There was a reduction in the rate of fatal stroke in the treatment group to 30% of that in the control group (95% confidence interval 11-84%, p less than 0.025). The rate of all strokes (fatal and non-fatal) in the treatment group was 58% of that in the control group (95% confidence interval 35-96%, p less than 0.03). The incidence of myocardial infarction and total mortality was unaffected by treatment. Questionnaires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment.