Ambulatory blood pressure monitoring in the elderly: features and perspectives.

Aging leads to a multitude of changes in the cardiovascular system that include a rise in blood pressure. Age-related changes in blood pressure are mainly attributable to an increase in systolic blood pressure, generally associated with a slight decrease diastolic blood pressure. This leads to a widening in pulse pressure. Ambulatory blood pressure monitoring is a useful tool to understand these processes and to refine cardiovascular risk assessment. In the light of emerging data in this area, we reviewed the main features of ambulatory blood pressure in elderly and discussed the evidence showing that ambulatory blood pressure is superior to clinic blood pressure to reflect the true pattern of blood pressure over time. Furthermore, we discussed the role of weight control obtained by fitness programs to prevent an excessive rise in blood pressure with age. A thorough understanding of these concepts is of paramount importance and has therapeutic implications in the growing population of elderly subjects with increased blood pressure.

Validation of a disease-specific health-related quality of life measure in adult Italian patients with systemic lupus erythematosus: LupusQoL-IT.

OBJECTIVE: The objective of this paper is to assess the validity of a linguistically validated version of the Lupus Quality of Life (LupusQoL(©)) in Italian patients affected by systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients completed the Italian version of the LupusQoL(©) and the Short Form (SF)-36. Disease activity was evaluated by the SLE disease activity Index-2000 (SLEDAI-2 K), and chronic damage by the Systemic Lupus International Collaborating Clinics/American College Rheumatology (ACR) Damage Index score (SDI). Internal consistency and test-retest reliability, convergent and discriminant validity were examined. Factor analysis with varimax rotation was performed. RESULTS: A total of 117 Italian SLE patients (M:F 13:104; mean age 40.6 ± 11.6 years, mean disease duration 127.5 ± 94.1 months) were recruited into the study. The Italian version of the LupusQoL(©) demonstrated substantial evidence of convergent validity in these patients when compared with equivalent items of the SF-36. In addition, the LupusQoL(©) discriminated between patients with different degrees of disease activity as measured by the SLEDAI-2 K. SLE patients with higher disease activity (SLEDAI-2K ≥4) showed poor QoL compared with those with lower disease activity (SLEDAI-2K <4), with significant differences in the domains of physical health, planning, burden to others and fatigue (p = 0.001, p = 0.04, p = 0.03, p = 0.04, respectively). The confirmatory factor analysis using the eight domain loadings of the 34 items showed a poor fit (χ(2)/degree of freedom (df) 2.26, χ(2 )= 1128.6 (p < 0.001), root mean square error of approximation (RMSEA) = 0.167; goodness-of-fit index (GFI) = 0.606, comparative fit index (CFI) = 0.649)). Screeplot analysis suggested a five-factor loading structure and confirmatory factor analysis result of which is similar to the eight-factor model. A good internal consistency was observed (Cronbach's α 0.89-0.91). Test-retest reliability was good to excellent between baseline and day 15 (intraclass correlation coefficient (ICC) 0.90-0.98). CONCLUSION: The Italian version of the LupusQoL(©) is a valid tool for adult patients with SLE.

Microalbuminuria and hypertension.

An elevated urinary albumin excretion (UAE) below the proteinuric level, i.e. microalbuminuria (MAU), has long been recognized as a marker of kidney disease and increased cardiovascular risk in both types of diabetes mellitus. Subsequent clinical evidence documented an association between MAU and other cardiovascular risk factors, target organ damage and risk of cardiovascular disease in the general population and in specific clinical contexts including essential hypertension. This article reviews the available evidence on the clinical value of MAU in subjects with essential hypertension. In these subjects, the reported prevalence of MAU ranges from about 4% to 46% across different studies and these differences may be explained by the huge intraindividual variability in UAE, age and ethnicity, discrepancies in the technique of measurement and different definitions of MAU. A direct and continuous association between UAE and blood pressure (BP) and left ventricular mass has been found in most studies. In contrast, it is not yet clear whether the association between UAE and other factors including age, gender, smoking, ethnicity, insulin resistance, lipids and obesity is independent or due to confounders, particularly BP. Several prospective studies disclosed an association between MAU and the risk of future cardiovascular disease. Of particular note, in some of these studies the incidence of major cardiovascular events progressively increased with UAE starting below the conventional MAU thresholds. Thus, besides being a direct risk factor for progressive renal damage, MAU can be considered a marker which integrates and reflects the long-term level of activity of several other detrimental factors on cardiovascular system. Antihypertensive treatment reduces UAE and such effect may be detected after just a few days of treatment. Among available antihypertensive drugs, angiotensin converting enzyme (ACE) inhibitors and the angiotensin II receptor antagonists seem to be superior to other antihypertensive drugs in reducing UAE. The dual blockade of the renin angiotensin system with an ACE inhibitor and an angiotensin II receptor antagonist is a new and promising approach to control UAE in hypertensive patients. Determination of MAU is recommended in the initial work-up of subjects with essential hypertension as suggested in the most recent European hypertension guidelines, even though, as upcoming evidence suggest, the periodic evaluation of this simple, inexpensive and predictive marker might be valuable and cost-effective.

Trends in hypertension management in Type I diabetes across Europe, 1989/1990 - 1997/1999.

AIMS/HYPOTHESIS: Our aim was to examine the change in the management of hypertension in patients with Type I (insulin-dependent) diabetes mellitus in Europe, between 1989-1990 and 1997-1999. METHODS: Seven-year changes in hypertension treatment and control (defined as blood pressure <130/85 mmHg) were examined in a large sample of Type I diabetic patients recruited from 26 centres involved in the EURODIAB Prospective Complications Study. Hypertension was defined as a systolic and/or diastolic blood pressure greater than 140 and/or 90 mmHg respectively, and/or use of blood pressure lowering drugs. RESULTS: Of 1866 Type I diabetic patients, 412 had hypertension at baseline and 631 at follow-up. A greater proportion of hypertensive patients were treated at follow-up (69% vs 40%, p<0.0001), which persisted after adjustment for age or centre. Of those who were treated, a modest increase in the proportion of those controlled for hypertension was found (41% vs 32%, p=0.048), which disappeared after adjustment for age. Among hypertensive patients with albuminuria, the proportions treated also increased, from 35% to 76% ( p<0.0001) in microalbuminuric and 64% to 95% ( p<0.0001) in macroalbuminuric patients. Control of hypertension in albuminuric patients did not change significantly and was below 50%. The use of more than one anti-hypertensive drug increased over a 7-year period, from 19% to 33% ( p<0.0001), and a marked increase was shown in the proportion of those taking an ACE inhibitor (from 57% to 82%, p<0.0001). CONCLUSION/INTERPRETATION: The management of hypertension in Type I diabetic patients across Europe has improved over a 7-year follow-up period. Optimal levels of blood pressure treatment and optimal levels of control have not yet been achieved.

Left ventricular mass and systolic dysfunction in essential hypertension.

A relation between left ventricular (LV) hypertrophy and depressed midwall systolic function has been described in hypertensive subjects. However, a strong confounding factor in this relation is concentric geometry, which is both a powerful determinant of depressed midwall systolic function and a correlate of LV mass in hypertension. To evaluate the independent contribution of LV mass to depressed systolic function, 1827 patients with never-treated essential hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography under two-dimensional guidance. Relative wall thickness was the strongest determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The significant inverse relation observed between LV mass and midwall fractional shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex-specific quintile of relative wall thickness, prevalence of subnormal afterload-corrected midwall systolic function was greater in subjects with, than in subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001) and relative wall thickness (P < 0.0001) were independent predictors of a reduced midwall fractional shortening. In conclusion, the inverse association between LV mass and midwall systolic function is partly independent from the effect of relative wall thickness. LV hypertrophy is a determinant of subclinical LV dysfunction independently of the concomitant changes in chamber geometry.

High-density lipoprotein cholesterol and left ventricular hypertrophy in essential hypertension.

OBJECTIVE: The proportion of left ventricular (LV) mass variability explained by blood pressure in essential hypertension is small, and several non-haemodynamic determinants of LV mass have been identified or hypothesized. This study examines the possible relation between blood lipids and LV mass in hypertension. DESIGN: Never-treated non-diabetic hypertensive patients. SETTING: Hospital hypertension outpatient clinics in Umbria, Italy. PATIENTS: We investigated the association between high-density lipoprotein (HDL)-cholesterol and echocardiographic LV mass in 1306 never-treated subjects with essential hypertension. Subjects with previous cardiovascular events, diabetes and current or previous antihypertensive or lipid-lowering therapy were excluded. RESULTS: HDL-cholesterol showed an inverse association with LV mass (r = -0.30, P < 0.001). No association was found between LV mass and total or low-density lipoprotein cholesterol. With multiple linear regression analysis we tested the independent contribution of several potential determinants of LV mass in women and in men. Average 24 h blood pressure (both pulse and mean), body mass index, height, stroke volume, age (all P < 0.01) and low HDL-cholesterol (P < 0.0001 in women, P < 0.001 in men) were associated with a greater LV mass in both sexes. Triglycerides showed a weak univariate association with LV mass in women (r = 0.11, P < 0.02), which did not hold in a multivariate analysis. CONCLUSIONS: Low HDL-cholesterol is an independent predictor of LV mass in untreated hypertensive subjects. Common hormonal and metabolic mechanisms, including insulin resistance, could explain this association, which may contribute to the adverse prognostic significance of low HDL-cholesterol levels.

Optimizing assessment of carotid and femoral intima-media thickness in essential hypertension.

Large artery intima-media thickness (IMT) is considered an integrated marker for the total individual burden of arteriosclerosis, and a graded index for cardiovascular risk. However, several different aggregate indexes of IMT on B-mode ultrasound have been used by various investigators, and the optimal number of IMT readings is currently unsettled. In 128 newly diagnosed, never treated, uncomplicated hypertensive subjects aged <55 years (43 +/- 9 years, blood pressure [BP] 152/99 mm Hg), we measured left ventricular mass (M-mode echocardiography, average of five or more measurements) and IMT of common carotid and common femoral arteries. For each segment, 12 IMT measurements were performed, and the average of 1 and 3 readings (right far wall), 6 readings (right side), and 12 readings (right and left side, far and near wall, 3 sampling points) was analyzed. The relation of IMT with left ventricular mass increased progressively with increasing number of readings, from 0.35 (1 reading) to 0.51 (12 readings) for common carotid artery, and from 0.31 to 0.56 for common femoral artery (both P <.001). For each 0.2-mm increase in common femoral IMT, the age-adjusted relative risk of having left ventricular hypertrophy was 1.31 for 1 reading, and increased up to 3.59 for the average of 12 readings. In summary, the association of IMT with left ventricular mass depends strongly on the number of IMT readings. The average of several readings in each segment, including right and left side and far and near wall, carries the closest association to left ventricular mass, and should be preferred for clinical purposes in hypertensive subjects.

Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension.

BACKGROUND: It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension. METHODS AND RESULTS: A total of 2363 initially untreated hypertensive patients (mean age 51+/-12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m(2)). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG conferred an increased risk for cerebrovascular events (relative risk [RR] 1.79; 95% CI 1.17 to 2.76). LVH by echocardiography also conferred a higher risk for cerebrovascular events (RR 1.64; 95% CI 1.07 to 2.68). For each increase in LV mass of 1 SD (29 g/m(2)), there was a significant independent increase in the risk for cerebrovascular events (RR 1.31; 95% CI 1.09 to 1.58). CONCLUSIONS: In apparently healthy patients with essential hypertension, LVH diagnosed by ECG or echocardiography confers an excess risk for stroke and transient ischemic attack independently of BP and other individual risk factors.

Short daily hemodialysis: blood pressure control and left ventricular mass reduction in hypertensive hemodialysis patients.

Several retrospective and uncontrolled prospective studies reported blood pressure (BP) normalization and left ventricular mass (LVM) reduction during daily hemodialysis (DHD). Conversely, the burden of these major independent risk factors is only marginally reduced by the initiation of standard thrice-weekly dialysis (SHD), and cardiovascular events still represent the most common cause of death in hemodialysis patients. Therefore, we performed a randomized two-period crossover study to compare the effect of short DHD versus SHD on BP and LVM in hypertensive patients with end-stage renal disease. We studied 12 hypertensive patients who had been stable on SHD treatment for more than 6 months. At the end of 6 months of SHD and 6 months of DHD in a sequence of randomly assigned 24-hour ambulatory BP monitoring, echocardiography and bioimpedance were performed. Throughout the study, patients maintained the same Kt/V. A significant reduction in 24-hour BP during DHD was reported (systolic BP [SBP]: DHD, 128 +/- 11.6 mm Hg; SHD, 148 +/- 19.2 mm Hg; P < 0.01; diastolic BP: DHD, 67 +/- 8.3 mm Hg; SHD, 73 +/- 5.4 mm Hg; P = 0.01). The decrease in BP was accompanied by the withdrawal of antihypertensive therapy in 7 of 8 patients during DHD (P < 0.01). LVM index (LVMI) decreased significantly during DHD (DHD, 120.1 +/- 60.4 g/m(2); SHD, 148.7 +/- 59.7 g/m(2); P = 0.01). Extracellular water (ECW) content decreased from 52.7% +/- 11.4% to 47.6% +/- 7.5% (P = 0.02) and correlated with 24-hour SBP (r = 0.63; P < 0.01) and LVMI (r = 0.66; P < 0.01). In conclusion, this prospective crossover study confirms that DHD allows optimal control of BP, reduction in LVMI, and withdrawal of antihypertensive treatment. These effects seem to be related to reduction in ECW content.

Different prognostic impact of 24-hour mean blood pressure and pulse pressure on stroke and coronary artery disease in essential hypertension.

BACKGROUND: We tested the hypothesis that the steady and pulsatile components of blood pressure (BP) exert a different influence on coronary artery disease and stroke in subjects with hypertension. METHODS AND RESULTS: We analyzed data on 2311 subjects with essential hypertension. All subjects (mean age 51 years, 47% women) underwent off-therapy 24-hour ambulatory BP monitoring. Over a follow-up period of up to 14 years (mean 4.7 years), there were 132 major cardiac events (1.20 per 100 person-years) and 105 cerebrovascular events (0.90 per 100 person-years). After adjustment for age, sex, diabetes, serum cholesterol, and cigarette smoking (all P<0.01), for each 10 mm Hg increase in 24-hour pulse pressure (PP), there was an independent 35% increase in the risk of cardiac events (95% CI 17% to 55%). Twenty-four-hour mean BP was not a significant predictor of cardiac events after controlling for PP. After adjustment for age, sex, and diabetes (all P<0.05), for every 10 mm Hg increase in 24-hour mean BP, the risk of cerebrovascular events increased by 42% (95% CI 19% to 69%), and 24-hour PP did not yield significance after controlling for 24-hour mean BP. Twenty-four-hour PP was also an independent predictor of fatal cardiac events, and 24-hour mean BP was an independent predictor of fatal cerebrovascular events. CONCLUSIONS: In subjects with predominantly systolic and diastolic hypertension, ambulatory mean BP and PP exert a different predictive effect on the cardiac and cerebrovascular complications. Although PP is the dominant predictor of cardiac events, mean BP is the major independent predictor of cerebrovascular events.

Original articles prognostic value of combined echocardiography and ambulatory blood pressure monitoring in hypertensive patients at low or medium cardiovascular risk.

BACKGROUND: The clinical value of echocardiography and ambulatory blood pressure monitoring (ABPM) in hypertensive patients at low immediate risk of cardiovascular disease is still unknown. METHODS: Echocardiography and ABPM were performed in 715 untreated subjects with essential hypertension World Health Organization/International Society of Hypertension stage I or II and low or medium cardiovascular risk defined by the absence of diabetes, previous cardiovascular events, left ventricular (LV) hypertrophy at electrocardiography, proteinuria, stages III-IV retinopathy and creatinine levels > 106.08 mmoll (1.2 mg/dl) and the presence of one or two traditional risk factors. RESULTS: The LV mass was increased in 26.5% of these subjects. Subjects with a limited blood pressure reduction from day to night (non-dippers) were 11.3%. Over 1-13 years of follow-up, 31 subjects developed a first major cardiovascular event. The event rate (per 100 person-years) was 0.60 in the subgroup with a normal LV mass vs 1.63 in that with an increased LV mass (p < 0.017), and 0.74 in dippers vs 3.75 in non-dippers (p < 0.001). On multivariate analysis, the relative risk of cardiovascular events was 1.70 (95% confidence interval-CI 1.23-2.36) for each 11 g/m(2.7) increment in LV mass (p < 0.01), and 2.77 (95% CI 1.12-6.83) in non-dippers vs dippers (p < 0.05). Overall, on the basis of results of combined echocardiography and ABPM, 33% of subjects were at increased risk of future cardiovascular events. CONCLUSIONS: At standard first-line work-up performed on hypertensive subjects at low or medium cardiovascular risk, combined echocardiography and ABPM identify an increase in the risk of subsequent cardiovascular disease in one third of subjects.

High-normal serum creatinine concentration is a predictor of cardiovascular risk in essential hypertension.

BACKGROUND: Determination of serum creatinine concentration is recommended in all patients with hypertension as a marker of target organ damage. However, the possibility that creatinine values within the reference range might contribute to stratification of cardiovascular risk in essential hypertension has never been tested. PATIENTS AND METHODS: In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale Study, for up to 11 years (mean, 4 years) we followed up 1829 white patients with hypertension (mean +/- SD age, 51 +/- 12 years; 53% men; office blood pressure, 157/98 mm Hg) free of cardiovascular events and with normal pretreatment creatinine levels (men, <136 micromol/L [<1.5 mg/dL]; women, <120 micromol/L [<1.4 mg/dL]) who also underwent 24-hour blood pressure monitoring and electrocardiography before therapy. RESULTS: During follow-up, there were 175 fatal or nonfatal major cardiovascular morbid events (2.4 per 100 patient-years). Event rate increased progressively from the first to the fourth sex-specific quartiles of creatinine distribution (1.5, 2.3, 2.3, and 3.5 per 100 patient-years; P =.003 by log-rank test). After adjustment (in a multivariate Cox model) for age, sex, diabetes, cholesterol, smoking, left ventricular hypertrophy, and 24-hour pulse and mean blood pressures (P<.05 for all), creatinine concentration was an independent adverse predictor of cardiovascular morbid events (P =.01). The observed excess risk was 1.30 (95% confidence interval, 1.07-1.59) for a 20-micromol/L (0.23-mg/dL) increase in creatinine concentration. CONCLUSIONS: A serum creatinine value within the reference range is a predictor of cardiovascular morbidity in white patients with essential hypertension. Its prognostic value persists after adjustment for several powerful confounders, including average 24-hour blood pressure and left ventricular hypertrophy.

Prognostic value of midwall shortening fraction and its relation with left ventricular mass in systemic hypertension.

We followed 1,778 subjects (up to 12 years) with essential hypertension who underwent echocardiography at the time of their initial diagnostic workup. There were 166 major cardiovascular events during follow-up and the prognostic value of the midwall shortening fraction did not remain significant after controlling for left ventricular mass.

[Blood pressure components and target organ damage]. / Quale componente pressoria influenza maggiormente il danno d'organo?

In a given hypertensive patient, clinically overt cardiovascular disease is often preceded by a number of signs of target organ damage at the cardiac, arterial and renal levels. These changes have been collectively defined "pre-clinical cardiovascular disease", and carry a substantially increased risk for future cardiovascular complications. The present article examines the relationship between blood pressure components and target organ damage in essential hypertension. Arterial pressure can be split into a steady component (represented by the mean arterial pressure), which is a measure of the average level of pressure in a given artery, and a pulsatile component (represented by the pulse pressure), which estimates the cyclic oscillations around the mean. All blood pressure components show a positive, linear correlation with left ventricular mass, both in the general population and in patients with essential hypertension. However, the association is significantly stronger for the steady blood pressure components (systolic and mean arterial pressure) than for the pulse pressure. Available data regarding arterial changes suggest that the association is partly different. The majority of available studies show that large-artery intima-media thickening and discrete atherosclerotic plaques are better predicted by pulse pressure than by other blood pressure components, particularly in the elderly. After the age of 60, there is clear-cut evidence for a J-shaped relationship between diastolic blood pressure and arterial thickening or plaques, while for younger age groups the relationship appears to be linear. These data might offer an explanation for the observed superior prognostic value of pulse pressure in the elderly. The relationship between the different blood pressure components and renal damage is more controversial. In summary, pulsatile, cyclic stress (as represented by pulse pressure) appears to be more important in determining arterial changes in hypertensive patients, while steady blood pressure components play a dominant role in the development of hypertensive left ventricular hypertrophy.

Subclinical left ventricular dysfunction in systemic hypertension and the role of 24-hour blood pressure.

The relation between blood pressure (BP) and left ventricular (LV) systolic function in systemic hypertension is controversial. We assessed the relation of LV midwall fractional shortening (FS) to 24-hour BP in 1,702 never-treated hypertensive subjects (age 48 +/- 12 years), who underwent 24-hour BP monitoring and echocardiography. Stress-corrected endocardial and midwall FS (the latter calculated taking into account the epicardial migration of midwall during systole) were predicted in hypertensives on the basis of the values observed in 130 healthy normotensives (age 43 +/- 13 years, office BP 126/78 mm Hg). Subjects below the fifth percentile of observed-to-predicted FS had depressed LV function. The use of midwall FS resulted in an increase from 3.5% to 17.5% in the proportion of patients with depressed chamber function. Compared with the group with normal function, subjects with low midwall LV function had similar office systolic BP (155 +/- 21 vs 154 +/- 17 mm Hg), but increased 24-hour systolic BP (140 +/- 17 vs 133 +/- 12 mm Hg, p <0.001). Midwall FS had a closer negative relation to 24-hour systolic BP than to office systolic BP (r = -0.27 vs -0.08, p <0.001), whereas this difference was not apparent for diastolic BP (r = -0.23 vs -0.20). Compared with endocardial FS, midwall FS had a stronger inverse association to LV mass (r = -0.45 vs -0.16, p <0.001). Thus, an increased 24-hour BP load may chronically lead to depressed myocardial function in systemic hypertension in the absence of clinically overt heart disease.

Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study.

BACKGROUND: The long-term effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on ambulatory blood pressure and cardiac performance have never been examined comparatively. OBJECTIVE: We compared losartan and enalapril in their long-term effects on office and ambulatory blood pressure, cardiac structure and function, and routine biochemical tests. DESIGN: In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, 22 hypertensive subjects were studied with ambulatory blood pressure monitoring and echocardiography before and after an average of 3.3 years of treatment with losartan 50mg daily. These subjects were matched in a 1:3 ratio with a group of 66 subjects treated with enalapril 20mg daily. Case-control sampling was based on age (+/-5years), sex, pre-treatment office blood pressure (+/-5mmHg) and ambulatory blood pressure (+/-5mmHg), and duration of treatment (+/-6months). An additional group of subjects who interrupted their treatment with enalapril (n=18) or losartan (n =2) because of unwanted effects before execution of the follow-up study was not included in the analysis. RESULTS: Hydrochlorothiazide was added during follow-up in order to optimize blood pressure control (office blood pressure <140mmHg systolic and 90mmHg diastolic) in 10 subjects (45%) in the losartan group and 34 subjects (52%) in the enalapril group. Office and ambulatory blood pressures were lowered to a similar extent by losartan and enalapril. Left ventricular mass decreased from 98 to 87g/m(2) with losartan (P <0.01) and from 98 to 89 g/m(2) with enalapril (P <0.01). The change in left ventricular mass over time was more closely associated with the change in ambulatory blood pressure than with office blood pressure in both groups. Left ventricular internal diameter did not change with either drug. The endocardial shortening fraction, mid-wall shortening fraction and Doppler indexes of active diastolic relaxation did not change with either drug. None of the biochemical parameters showed a significant change. Serum uric acid showed a slight and non-significant reduction only in the losartan group. CONCLUSION: In this case-control study in uncomplicated subjects with essential hypertension, losartan and enalapril, alone or combined with a diuretic, effectively and equally lowered office and ambulatory blood pressure and induced a significant reduction in left ventricular mass during long-term treatment. Left ventricular systolic and diastolic function remained unchanged with either regimen.

Manometric investigation of anorectal function in early and late stage Parkinson's disease.

Abnormal gastrointestinal function is relatively frequent in Parkinson's disease, and constipation is a disturbing symptom in many patients. However, it remains to be established whether anorectal abnormalities are characteristic of the late stages of the disease. Clinical and anorectal manometric function were investigated in groups of early and late stage parkinsonian patients. Thirty one patients (19 men, 12 women, age range 22 to 89 years) entered the study. The disease severity was assessed by Hoehn and Yahr staging: there were four (12.9%) stage I, seven (22.6%) stage II, 10 (32.2%) stage III, and 10 (32.2%) stage IV patients. Anorectal variables were measured by standard manometric equipment and techniques. Values obtained in early stage patients (Hoehn and Yahr stage I and II) were compared with those obtained in late stage patients (Hoehn and Yahr stage III and IV). Overall, more than 70% of patients complained of chronic constipation, with chronic laxative use reported in more than 30%. Late stage patients were slightly older than their early stage counterparts. Pelvic floor dyssynergia was documented in more than 60% of patients. Manometric variables were not different in the two groups. In conclusion, defecatory dysfunction is frequent in Parkinson's disease, it is not confined to late stage patients, and it is found early in the course of the disease. This has potential implications for a targeted therapeutic approach.

Cerebrospinal fluid pyruvate levels in Alzheimer's disease and vascular dementia.

Increased amounts of CSF pyruvate and lactate were found in patients with AD and patients with vascular dementia (VaD). In the AD group, CSF pyruvate values did not show any overlap with those obtained in controls; within the VaD group, the highest values were observed in possible VaD cases. A significant correlation between the severity of dementia and these biochemical parameters was also observed in both AD and possible VaD. The similarities of CSF pyruvate patterns observed in AD and possible VaD patients implicate a neurodegenerative component in this VaD subgroup.

Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study.

The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.