Diagnostic tools for the study of vascular cognitive dysfunction in hypertension and antihypertensive drug research.

Arterial hypertension is one of the main risk factors for cerebrovascular diseases, and antihypertensive treatment has significantly reduced their associated mortality. However, morbidity has not been reduced to a similar extent and a still increasing number of patients suffers from recurring strokes and from the disabling consequences of cerebrovascular diseases and develops progressive cognitive impairment. It is still debated to what extent antihypertensive treatment may prevent the development of cognitive dysfunction, due to the lack of a focused approach to vascular cognitive impairment, to the lack of a systematic study of the early phases of dementia, and to the use of diagnostic tests that are not sensitive and specific for a slow onset clinical condition, such as dementia. The aim of the present expert consensus report is to enlist the diagnostic tools that are currently available to assess mild cognitive impairment (MCI) and early dementia and that are sensitive and specific enough to be used in observational, longitudinal, and interventional clinical research studies, aiming to investigate the impact of antihypertensive drugs on vascular dementia (VD).

Aldosterone and refractory hypertension: a prospective cohort study.

BACKGROUND: Resistant hypertension is common in clinical practice. The aim of our study was to evaluate inappropriate aldosterone activity in causing resistance to antihypertensive therapy. METHODS: Among the patients consecutively evaluated for the first time between 1995 and 2001, we selected all those (n = 157) with an aldosterone-to-renin ratio (ARR) >or=25 (ng/dL)/(ng/mL/h), and plasma aldosterone >or=12 ng/dL. Eight patients with Conn adenoma were excluded from the study. Fifty-eight were diagnosed as idiopathic aldosteronism (IHA), the other 91 patients, who did not meet the criteria for primary aldosteronism, were operatively classified as aldosterone-associated hypertension (AAH). As a control group, we randomly chose 160 patients with essential hypertension and plasma aldosterone <12 ng/dL (EH). Antihypertensive treatment was given in accordance to World Health Organization Guidelines (1999). The study end point was blood pressure (BP) <140/90 mm Hg. RESULTS: During follow-up (22 +/- 2 months), 24 (41.4%) patients with IHA, 35 (38.5%) with AAH, and 72 (54.0%) with EH reached the end point. According to survival analysis, AAH and IHA patients reached the end point in a smaller fraction and in a longer time compared with EH patients, with no difference between IHA and AAH. At the end of follow-up, IHA and AAH patients had higher diastolic BP than EH patients with no difference between IHA and AAH. CONCLUSIONS: Patients with elevated aldosterone plasma levels develop resistant hypertension, even in the absence of clinically diagnosed primary aldosteronism. Their identification will allow a targeted therapy and a more effective BP reduction.

Blood pressure in acute ischemic stroke and mortality: a study with noninvasive blood pressure monitoring.

BACKGROUND: In acute ischemic stroke, a transient elevation of blood pressure is common; its significance and its relationship with the neurological outcome are still unclear. METHODS: In 71 consecutive patients with acute ischemic stroke, aged 25-94 years, admitted to our unit, we investigated the relationships between the blood pressure variation during the first 24 h and mortality at 3 months (study endpoint). Neurological status was assessed with the National Institutes of Health Stroke Scale. Blood pressure was measured with bedside noninvasive blood pressure monitoring every 15 min. The mean of four measurements at the emergency department and the mean of 12 measures (during a 3-h interval) at 12 and at 24 h after stroke onset were considered for analysis. Antihypertensive treatment was given in accordance with the Recommendations for Stroke Management of European Stroke Initiative. RESULTS: In the whole series, 21% were atherothrombotic, 32% cardioembolic, 34% lacunar, and 13% of unknown or other cause. Blood pressure was 160+ or -3/86+ or -2 mmHg at the emergency department, 148+ or -3/82+ or -2 mmHg at 12 h, and 147+ or -3/81+ or -2 mmHg at 24 h (P<0.05). Four patients (11%) of those in whom mean blood pressure decreased >5 mmHg, and 12 (33%) of the others, in whom mean blood pressure decreased < or =5 mmHg or did not decrease, reached the endpoint (P<0.05). According to the multivariate Cox model, NIHSS score at the emergency department (95% confidence interval: 1.025-1.238, P=0.013) and age (95% confidence interval: 1.007-1.259, P=0.038) were predictors of reaching the endpoint, whereas mean blood pressure reduction 24 h after stroke onset had a protective effect (95% confidence interval: 0.845-0.995, P=0.038). Diabetes, mean blood pressure at the emergency department and the need for antihypertensive therapy did not correlate with the outcome. CONCLUSIONS: Noninvasive blood pressure monitoring during the first 24 h of acute ischemic stroke may be useful in the prognostic stratification by showing moderate blood pressure decrease, either spontaneous or drug induced, which is associated with a favorable prognosis at 3 months.

RGS2 expression and aldosterone: renin ratio modulate response to drug therapy in hypertensive patients.

OBJECTIVE: RGS2 (regulators of G-protein signalling) is a negative regulator of Galphaq protein signalling, which mediates the action of several vasoconstrictors. Low RGS2 expression increases G-protein-coupled signalling in hypertensive patients. The aim of the present study was to correlate RGS2 expression in peripheral blood mononuclear cells (PBMs) with response to antihypertensive therapy in never-treated patients with essential hypertension. METHODS AND DESIGN: RGS2 expression was measured by real-time quantitative RT-PCR in peripheral blood mononuclear cells (PBMs) from 102 essential hypertensives. The diagnosis of essential hypertension was based on all clinically required tests, including the captopril suppression test. Antihypertensive treatment was given in accordance to international guidelines. End-point of the study was systolic blood pressure (BP) less than 140 mmHg and diastolic BP less than 90 mmHg with three or less different antihypertensive agents, which identified responders to treatment. Resistant hypertension was defined as the failure to control systolic and/or diastolic BP despite at least three different classes of antihypertensive agents, including a diuretic. RESULTS: During follow-up, 85 (83%) patients reached the end point (responders). Resistant hypertensives (n = 17, 17%) were older, had higher baseline BP, plasma aldosterone and aldosterone: renin ratio (ARR) and lower plasma renin activity than patients who reached the end point. RGS2 was negatively correlated to systolic BP at enrollment and significantly lower in PBMs from resistant hypertensives in comparison with patients that reached BP goal. According to logistic regression analysis, high RGS2 expression was predictor of reaching BP goal, whereas high ARR after captopril, age and systolic pressure at enrolment were predictor of resistant hypertension. CONCLUSION: RGS2 expression affects the response to antihypertensive treatment. Reduced RGS2 expression contributes to resistance to antihypertensive agents through poor negative feedback on the effects of aldosterone and of other vasoactive agents.

Obsessive-Compulsive and Post Traumatic Avoidance Symptoms Influence the Response to Antihypertensive Therapy: Relevance in Uncontrolled Hypertension.

AIM: To investigate the association of uncontrolled hypertension with psychological factors associated with high cardiovascular morbidity and mortality (type D personality, depression, posttraumatic stress-related symptoms). METHODS: 205 consecutive outpatient hypertensives completed three questionnaires evaluating Type D personality (DS 16), post traumatic symptoms (revised Impact of Events Scale), symptoms of anxiety, hostility, depression and obsessive-compulsive traits (subscales of the Symptom Checklist). Uncontrolled hypertension was diagnosed when clinic sitting blood pressure was above 140/90 mmHg (130/80 in the presence of diabetes or nephropathy), despite reported adherence to treatment with at least three antihypertensive medications, including a diuretic. RESULTS: Uncontrolled hypertension (39%), was predicted by lower scores at Symptom Checklist obsessive-compulsive subscale and higher number of post traumatic avoidance symptoms, older age, diabetes, higher systolic pressure at first visit and longstanding hypertension. Type D personality correlated with depression, hostility, anxiety, compulsiveness, history of malignancy, and older age, but not with uncontrolled hypertension. CONCLUSIONS: Uncontrolled hypertension is associated with low obsessionality and avoidance symptoms, which reduce compliance to treatment. On the contrary, type D personality is not correlated with uncontrolled hypertension, as it includes compulsiveness, which improves compliance. A multidisciplinary approach to the hypertensive patient is mandatory to establish if the psychological profile affects compliance.

Problems related to short-term antihypertensive therapy in acute ischemic stroke.

Hypertension is a common early finding after an acute ischemic stroke, even in previously normotensive patients. But its significance and proper management are a matter of debate, because of the lack of adequately powered randomized clinical trials. A close analysis of observational and interventional trials, published so far, fails to convince that an early antihypertensive therapy is needed and beneficial. During the first 24-48 hr after ischemic stroke, only blood pressure values repeatedly higher than 220/120 mmHg require antihypertensive treatment to keep blood pressure levels in the range of 180-220 mmHg systolic and 100-120 diastolic. Blood pressure reduction should be cautious with the aim of keeping the pressure at relatively high values (180/100-105 in previously hypertensive patients and 160-180/90-100 in previously normotensive patients). The usefulness of increasing blood pressure with vasopressive agents in selected patients with ischemic stroke deserves adequate testing with randomized clinical trials.