Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5-hexanedione concentration in the sciatic nerve, serum, and urine of rats

PURPOSE: The aim of this study was to examine the associations among fasting insulin, adiposity, waist girth, and blood pressure among a nondiabetic multiethnic population. METHODS: A cross-sectional study was performed among 25-44-year-old African-Americans (n = 159), Cuban-Americans (n = 128), and non-Hispanic whites (n = 207) selected from Dade County, Florida. Fasting insulin levels were correlated with resting blood pressure level within each ethnic group. The separate effects of percentage body fat and waist girth on the association between blood pressure and insulin were analyzed in multiple linear regression and analysis of covariance. RESULTS: Fasting insulin was positively associated with systolic (r = 0.26-0.39; P < 0.01) and diastolic blood pressure (r = 0.19-0.30; P = 0.10 to P < 0.001) among women of all ethnic groups and among non-Hispanic white men (r = 0.27; P < 0.05). Stepwise linear regression analyses revealed statistically significant associations between systolic and diastolic blood pressure and fasting insulin level in non-Hispanic whites independent of other covariates, including sex and percentage body fat (P < 0.001). Fasting insulin was also independently and significantly related to systolic blood pressure among African-Americans (P = 0.02). Among Cuban-Americans, sex and percentage body fat were the main correlates of blood pressure level. Analysis of covariance revealed a relationship between insulin and blood pressure that was independent of waist girth among men and women. CONCLUSIONS: Fasting insulin level and blood pressure were positively associated among African-Americans and non-Hispanic whites. This association was not entirely due to the common association with percentage body fat or waist girth.     

Microalbuminuria in essential hypertensives in treatment for hypertension

Urinary albumin excretion (UAE) was evaluated in 26 subjects with essential hypertension and no diabetes (5 men, 21 women; 19 whites and 7 blacks), with creatinine clearance (Ccreat) > or = 75 ml/min/1.73 m2, in individualized treatment with various antihypertensive drugs. Clinical and laboratorial data were the following: mean age, 53 +/- 2 years (SEM); duration of hypertension, 14.9 +/- 2.2 years; body mass index (BMI), 26.8 +/- 0.7; arterial blood pressure, 142 +/- 4/89 +/- 3 mmHg; serum creatinine, 0.8 +/- 0.03 mg/dL; Ccreat, 99.3 +/- 3.8 ml/min/1.73 m2 and UAE, 9.3 +/- 1.5 micrograms/min. No significant difference was found when data were evaluated for gender and race. Microalbuminuria, defined as UAE > 13.9 micrograms/min, was found in 19% of the hypertensives (range: 16.3 to 28.1 micrograms/min). UAE correlated positively and significantly with systolic (r = 0.6309; P = 0.0005), diastolic (r = 0.4146; P = 0.0352), and mean blood pressure (r = 0.5000; P = 0.0093). The correlation between UAE and systolic pressure was stronger than with diastolic pressure. There was a positive and significant correlation between BMI and UAE values (r = 0.5623; P = 0.0028), and between BMI values with those of systolic (r = 0.5271; P = 0.0057) and mean blood pressure (r = 0.3930; P = 0.470). No correlation was found between UAE and age, duration of hypertension or Ccreat. Systolic, diastolic and mean blood pressures were significantly higher in microalbuminuric than in non microalbuminuric hypertensives. Obese hypertensives presented higher mean values of UAE, systolic, diastolic and mean pressures than non obese.     

Isolated systolic hypertension and cognitive function in the aged. Experience of the Syst-Eur study

OBJECTIVE: To determinate cognitive status and its correlates in older patients with isolated systolic hypertension. METHODS: Syst-Eur is a double-blind placebo-controlled outcome trial conducted in European patients over 60 years of age with isolated systolic hypertension. Moreover, a side-project--the Vascular Dementia Project--is designed to assess cognitive functions and to follow-up their evolution to determine the influence of antihypertensive therapy on vascular dementia incidence. Cognitive functions were evaluated at entry with the MiniMental State Examination (MMSE) in 2250 patients included in Syst-Eur. Cognitive impairment was defined with a MMSE score < or = 23 and led to further evaluation. Baseline blood pressure (BP) was based on the average of six sitting blood pressure readings at three run-in visits 1 month apart. Statistical analysis used Spearman correlation. RESULTS: The MMSE was analysed in 1374 women and 751 men whose mean age was 70 years (range: 60-100). The median level of education expressed as the age at which they stopped their education at school, was 15 years. Baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg. Before randomisation in the trial, 899 (40%) patients had received antihypertensive therapy and 602 (27%) had experienced cardiovascular complications. The MMSE-scores ranged from 15 to 30 (median = 29). The maximal score of 30 was reached by 609 (30%) subjects. Among the 59 (3%) patients with a MMSE-score of 23 or less, 5 were considered to be demented according to the DSM IIIR criteria. The MMSE-scores decreased with advancing age in men (r = -0.16; p < 0.001) and women alike (r = -0.24; p < 0.001). In both men and women, they were positively correlated with the level of education (r = 0.30 and 0.32, respectively; p < 0.001). They were negatively correlated with systolic blood pressure (r = 0.10; p < 0.001) and slightly positively correlated with diastolic blood pressure (r = 0.05; p = 0.03). Previously treated patients or patients reporting cardiovascular complications at baseline had lower MMSE-scores than their non-treated counterparts or subjects without cardiovascular complications (median = 28 and 29, respectively, p < 0.003). CONCLUSION: In a European cohort of 2225 patients over 60 years of age with isolated systolic hypertension, the level of cognitive functions evaluated with the MMSE decreases with advancing age or lesser educational level. It also decreases with higher systolic blood pressure or lower diastolic blood pressure. The influence of antihypertensive therapy on cognitive status will be prospectively evaluated in Syst-Eur Vascular Dementia Project.     

Ambulatory 24-h blood pressure monitoring in healthy, middle-aged smokeless tobacco users, smokers, and nontobacco users

Ambulatory 24-h blood pressure monitoring was conducted in 135 healthy, normotensive, middle-aged (35 to 60 years) men, with no antihypertensive medication, to study the influence of habitual smokeless tobacco use (n = 47) and smoking (n = 29) on diurnal blood pressure and heart rate. Comparisons were made with nonusers of tobacco (n = 59). Adjustments were made for differences in age, body mass index, waist-hip ratio, physical fitness, and alcohol intake. Daytime ambulatory heart rates were significantly (P < .05) elevated in both smokeless tobacco users and smokers compared with nonusers (69 +/- 14 and 74 +/- 13 beats/min, respectively, versus 63 +/- 12 beats/min). In subjects > or = 45 years old, ambulatory daytime diastolic blood pressures were significantly elevated, on average by 5 mm Hg, in both smokeless tobacco users and smokers (P < .001) compared with nonusers. Clinical measurements of heart rate and systolic blood pressure in smokers were significantly lower compared with the ambulatory mean values. Nighttime measurements showed only minor differences between the tobacco habit groups. The higher heart rates and blood pressures noted during the daytime in smokers and smokeless tobacco users were most likely due to the effects of nicotine. A strong positive relationship was found between cotinine (major nicotine metabolite) and blood pressure in smokeless tobacco users (systolic blood pressure, r = 0.48, P < .001; diastolic blood pressure, r = 0.41, P = .005), whereas an inverse relationship was found in smokers (systolic blood pressure, r = -0.12, P = .47; diastolic blood pressure, r = -0.03, P = .84), indicating additional and more complex influences on vascular tone in smokers than the influence of nicotine in smokeless tobacco users.     

A cross-sectional analysis on relationships between maximum oxygen uptake and risk factors for cardiovascular diseases

We examined the relationships between maximum oxygen uptake (Vo2max) and cardiovascular risk factors including age (year), systolic blood pressure (mmHg), diastolic blood pressure (mmHg), serum total cholesterol level (mg/dl), serum high-density lipoprotein level (mg/dl), serum triglyceride level (mg/dl), blood glucose level (mg/dl), serum uric acid level (mg/dl), body fat (%bw), Body Mass Index (BMI), alcohol (points/day), cigarettes (/day), and physical activity (METs.exercise time/30 days). The alcohol point was defined as follows: beer 633ml = a glass of whiskey and water - sake 180ml = 1 point, and totaled at 30 days. The subjects of our study were 162 males (aged 40.6 +/- 13.1) and 133 females (aged 41.3 +/- 11.1) who underwent medical and physical examinations at the Fukui Industrial Health Center from April, 1991 to June, 1992. As a result of simple correlation analysis in males, Vo2max had significantly negative correlations with age (r = -0.223, p < 0.01), systolic blood pressure (r = -0.228, p < 0.01), diastolic blood pressure (r = -0.239, p < 0.01), or serum triglyceride level (r = -0.258, p < 0.001), serum uric acid level (p < 0.05), body fat (r = -0.230, p < 0.01), and BMI (r = -0.312, p < 0.001), and was positively correlated with physical activity (r = -0.249, p < 0.01). On the other hand, in females, age (r = -0.224, p < 0.01), systolic blood pressure (r = -0.222, p < 0.01), diastolic blood pressure (r = -0.267, p < 0.01), serum triglyceride level (r = -0.261, p < 0.001), body fat (r = -0.280, p < 0.01), and BMI (r = -302, p < 0.001), had significantly negative correlations with VO2max. However, partial correlations were tested after controlling body fat, BMI, cigarette, alcohol, physical activity, and age, none of the factors correlated with VO2max significantly. These findings suggest that the risk factors for cardiovascular diseases are related to VO2max, and the life style has an influence on these correlations. Thus, VO2max may be a comprehensive indicator for health promotion among the working population. Furthermore a longitudinal study is required to determine whether the increase in VO2max is related to the improvement in the risk of cardiovascular diseases.     

Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program

BACKGROUND: Population-based data are unavailable concerning the predictive value of orthostatic hypotension on mortality in ambulatory elderly patients, particularly minority groups. METHODS AND RESULTS: With the use of data from the Honolulu Heart Program's fourth examination (1991 to 1993), orthostatic hypotension was assessed in relation to subsequent 4-year all-cause mortality among a cohort of 3522 Japanese American men 71 to 93 years old. Blood pressure was measured in the supine position and after 3 minutes of standing, with the use of standardized methods. Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) of >/=20 mm Hg or in diastolic blood pressure of >/=10 mm Hg. Overall prevalence of orthostatic hypotension was 6.9% and increased with age. There was a total of 473 deaths in the cohort over 4 years; of those who died, 52 had orthostatic hypotension. Four-year age-adjusted mortality rates in those with and without orthostatic hypotension were 56.6 and 38.6 per 1000 person-years, respectively. With the use of Cox proportional hazards models, after adjustment for age, smoking, diabetes mellitus, body mass index, physical activity, seated systolic blood pressure, antihypertensive medications, hematocrit, alcohol intake, and prevalent stroke, coronary heart disease and cancer, orthostatic hypotension was a significant independent predictor of 4-year all-cause mortality (relative risk 1.64, 95% CI 1.19 to 2.26). There was a significant linear association between change in systolic blood pressure from supine position to standing and 4-year mortality rates (test for linear trend, P<0.001), suggesting a dose-response relation. CONCLUSIONS: Orthostatic hypotension is relatively uncommon, may be a marker for physical frailty, and is a significant independent predictor of 4-year all-cause mortality in this cohort of elderly ambulatory men.     

Use of backrest elevation in critical care: a pilot study

BACKGROUND: Use of lower backrest positions occurs frequently and is a factor in the development of ventilator-associated pneumonia. OBJECTIVES: To determine the usual bed elevation and backrest position in a medical intensive care unit and their relationship to hemodynamic status and enteral feeding. METHODS: Data were collected in a 12-bed medical respiratory intensive care unit for 2 months. A protractor was used to measure the elevation of the head of the bed. Hemodynamic status was defined by systolic, diastolic, and mean arterial blood pressure measurements retrieved from each patient's flow sheet. RESULTS: The sample included 347 measurements of 52 patients. Mean backrest elevation was 22.9 degrees, and 86% of patients were supine. Backrest position differed significantly (P = .005) among nursing shifts (days, evenings, nights) but not for systolic (r = -0.04, P = .49), diastolic (r = 0.01, P = .83), or mean arterial blood pressure (r = -0.01, P = .84). Backrest elevation did not differ significantly between patients who were receiving enteral feedings and patients who were not (P = .23) or between patients receiving intermittent versus continuous nutrition (P = .22). CONCLUSIONS: Use of higher levels of backrest elevation (> or = 30 degrees) is minimal and is not related to use of enteral feeding or to hemodynamic status. The rationale for using lower backrest positions for critically ill patients may be based on convenience, the patient's comfort, or usual patterns in the unit. However, the dangers of supine positioning and its relationship to aspiration and ventilator-associated pneumonia should not be minimized.     

Twenty-four-hour blood pressure changes in young Somalian blacks after migration to Italy

Blood pressure changes induced by migration from Somalia to Italy were studied in 25 normotensive clinical healthy blacks (aged 29 +/- 6 years) who had immigrated from Mogadishu to Florence. Basal and 24-h ambulatory blood pressure, venous compliance, and daily urinary electrolyte excretion were measured on arrival and 6 months later. After 6 months both basal pressure (P < .05 for systolic blood pressure, P < .01 for diastolic blood pressure) and 24-h blood pressure (P < .004 for systolic blood pressure, P < .01 for diastolic blood pressure) had significantly increased. Urinary sodium excretion had also increased (P < .001), whereas plasma renin activity was significantly reduced (P < .05). The ambulatory pressure increase was significantly related to the urinary sodium increase (r = 0.49; P < .01). At follow-up 8 of 25 blacks were hypertensive according to the WHO definition (basal diastolic blood pressure > 90 mm Hg). In conclusion, an increase in 24-h blood pressure is detectable after immigration and changes seems to be mainly related to higher sodium intake in the Western diet.     

Left atrial "stunning" following radiofrequency catheter ablation of chronic atrial flutter

Patients with autonomic neuropathy are more susceptible to insulin-induced hypotension than normal subjects, but the mechanisms are unclear. We quantitated the hemodynamic and metabolic effects of two doses of i.v. insulin (1 and 5 mU/kg.min, 120 min each) and several aspects of autonomic function in 28 patients with insulin-dependent diabetes mellitus (IDDM) and in 7 matched normal subjects under standardized normoglycemic conditions. The autonomic function tests included those predominantly assessing the integrity of vagal heart rate control (the expiration inspiration ratio during deep breathing and high frequency power of heart rate variability) and tests measuring sympathetic nervous function (reflex vasoconstriction to cold and blood pressure responses to standing and handgrip). During hyperinsulinemia, heart rate increased less (2 +/- 1 vs. 6 +/- 2 beats/min; P < 0.04) and diastolic blood pressure fell more (-3.1 +/- 1.2 vs. 0.9 +/- 2.1; P = NS) in the patients with IDDM than in the normal subjects. Forearm vascular resistance decreased significantly in the patients with IDDM [by -7.1 +/- 1.4 mm Hg/(mL/dL.min); P < 0.001 for high vs. low dose insulin], but not in the normal subjects (-0.1 +/- 2.5 mm Hg/(mL/dL.min; P = NS). Reflex vasoconstriction to cold was inversely correlated with the decreases in diastolic (r = -0.51; P < 0.005) and systolic (r = -0.59; P < 0.001) blood pressure and forearm vascular resistance (r = -0.53; P < 0.005), but not with the change in heart rate. The expiration inspiration ratio was, however, directly correlated with the insulin-induced change in heart rate (r = 0.63; P < 0.001), but not with diastolic or systolic blood pressure or forearm vascular resistance. Whole body (48 +/- 2 vs. 67 +/- 5 mumol/kg.min; P < 0.005) and forearm (44 +/- 4 vs. 67 +/- 8 mumol/kg.min; P < 0.05) glucose uptake were significantly lower in the IDDM patients than in the normal subjects. The latter could be attributed to a defect in the forearm glucose arterio-venous difference (1.5 +/- 0.1 vs. 2.2 +/- 0.2 mmol/L, respectively; P < 0.01), but not in blood flow. We conclude that both impaired vagal heart rate control and sympathetic nervous dysfunction exaggerate the hemodynamic effects of insulin in patients with IDDM and could contribute to insulin-induced hypotension.     

Molecular analysis of the Drosophila catalase gene

OBJECTIVE: To determine whether genetic and non-genetic components of interindividual variation in systolic and diastolic blood pressure are constant throughout the day or are time or activity dependent. METHODS: We obtained 24 h ambulatory blood pressure recordings in 263 members of 68 unrelated nuclear families (i.e. parents and their offspring) representative of the Caucasian population of Rochester, MN, USA. Using the time each patient got into bed as a reference point, we identified 198 records in which this reference point was preceded by eight consecutive active hours (out of bed) and followed by four consecutive inactive hours (in bed) in which four or more blood pressure readings taken each hour were judged to be technically satisfactory. For each hourly mean for systolic and diastolic blood pressure, we estimated total interindividual variance, variance associated with concomitant variables (generation; sex within generation strata; and age, height, weight, body mass index, and abdomen-to-hip ratio within generation and sex strata), and variance associated with additive genetic effects (i.e. the chief cause of resemblance between relatives). To assess trends in each component of interindividual blood pressure variance over the 12 h period, we estimated the slope of the linear regression line fit to the hourly estimates. RESULTS: For systolic blood pressure, total interindividual variance did not change significantly (slope of regression line = -0.23, P = 0.717). In contrast, total interindividual variance for diastolic blood pressure was greater during active hours than inactive hours (slope of regression line = -5.53, P < 0.001). For both systolic and diastolic blood pressure, variance associated with the concomitant variables was greater during active hours than during inactive hours (for systolic blood pressure slope of regression line = -2.98, P = 0.001; for diastolic blood pressure slope of regression line = -6.14, P < 0.001). Likewise, for both systolic and diastolic blood pressure, variance associated with additive genetic effects was also greater during active hours than during inactive hours (for systolic blood pressure slope of regression line = -1.65, P = 0.090; for diastolic blood pressure slope of regression line = -1.47, P = 0.018). CONCLUSIONS: This study demonstrates that components of interindividual variation in blood pressure are not constant, but are time or activity dependent.     

Accuracy of a new wrist cuff oscillometric blood pressure device: comparisons with intraarterial and mercury manometer measurements

Accurate measurement of arterial blood pressure is of great importance for the diagnosis and treatment of hypertension. Because of the chronic nature of antihypertensive drug therapy, the involvement of the patient in blood pressure control is desirable. Such an involvement, however, is only feasible if simple, user-friendly, and precise blood pressure measurement devices are available. In this study we tested a new wrist cuff oscillometric blood pressure measurement device in 100 consecutive patients undergoing cardiac catheterization. Blood pressures were simultaneously taken intraarterially (axillary artery) and with a mercury manometer and stethoscope or noninvasive measurement device (OMRON R3). Intraarterial measurements were directly compared with two measurements taken in random order with either an arm cuff mercury manometer or the wrist cuff device. Systolic and diastolic blood pressure as assessed with the mercury manometer was higher, especially when compared with the intraarterial and the wrist cuff values, which were comparable. Correlations of blood pressure values with intraarterial measurement were 0.86 systolic and 0.75 diastolic (P < .01) for the wrist cuff and 0.84 systolic (P < .01) and 0.59 diastolic (P < .05) for the mercury manometer measurements. Reproducibility of both measurements was good for the wrist cuff device ([systolic/diastolic]: r = 0.94/0.92; P < .01) and the mercury manometer (r = 0.97/0.88; P < .01). Both methods overestimated high diastolic values, whereas only the wrist cuff underestimated high systolic values. Thus, the new oscillometric wrist cuff blood pressure measurement device measures arterial blood pressure with great accuracy and reproducibility. As compared with intraarterial values, the wrist cuff device overestimated high diastolic and underestimated high systolic blood pressure values. Blood pressure values as measured by the mercury manometer were higher than intraarterial values and those of the wrist cuff. Both noninvasive devices overestimated high diastolic values.     

Atherosclerosis and left ventricular hypertrophy: persisting problems in treated hypertensive patients

OBJECTIVES: First, to determine whether hypertensive patients managed in general practice have more advanced atherosclerosis and left ventricular hypertrophy than matched normotensive patients from the same practices. Second, to investigate the associations of several potentially modifiable factors with these vascular and cardiac outcomes. DESIGN AND METHODS: We performed a case-control study of 500 hypertensive cases (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or receiving treatment) and 506 age- (mean 61 years) and sex- (54% female) matched normotensive controls recruited from general practices. Carotid artery far wall thickness (CWT), assessed by B-mode ultrasound, and left ventricular mass (LVM), assessed by M-mode echocardiography, were the main study outcome measures. RESULTS: Mean systolic/diastolic blood pressure levels in the 399 treated cases (145/87 mmHg) were lower than those in untreated cases (158/94 mmHg) but higher than those in controls (133/82 mmHg, all P < 0.0001). Mean body mass index (BMI) and total triglyceride levels were higher and high-density lipoprotein cholesterol was lower in cases than in controls (all P < 0.0004). Mean CWT was 10% greater in cases than in controls and LVM was 14% greater (both P < 0.001), but both were similar in treated and untreated cases (P > 0.05). In multivariate analyses, blood pressure and BMI were both directly and independently related to CWT and LVM (both P < 0.0001). CONCLUSIONS: In this study, hypertensive patients managed in general practice - whether treated with antihypertensive drugs or not - had more advanced atherosclerosis and left ventricular hypertrophy than did matched normotensive patients. Efforts to lower blood pressure further and to reduce BMI could potentially reduce these differences, and this might lead to a reduction in the risk of major cardiovascular events.     

I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives

Moxonidine is an I1-imidazoline receptor agonist that reduces blood pressure in hypertensives. Experimental data suggest that moxonidine inhibits central sympathetic activity. However, whether such a mechanism is involved in vivo in humans is still unclear. We investigated the effects of 0.4 mg moxonidine orally on muscle sympathetic nerve activity and heart rate in an open study in 8 healthy volunteers. Furthermore, we studied the effects of 0.4 mg moxonidine on muscle sympathetic nerve activity, heart rate, blood pressure, 24-hour blood pressure profile, and hormone plasma levels in 25 untreated hypertensives in a double-blind, placebo-controlled study. Moxonidine decreased muscle sympathetic nerve activity in both healthy volunteers (P<0.05 versus baseline) and hypertensives (P<0.02 versus placebo). Plasma norepinephrine also decreased (P<0. 01), whereas plasma epinephrine and renin levels did not change (P=NS). Furthermore, moxonidine decreased systolic (P<0.0001) and diastolic (P<0.001) blood pressure. Heart rate decreased after moxonidine in healthy subjects (P<0.05); in hypertensives, heart rate decreased during the night hours (P<0.05) but not during daytime (P=NS). Plasma levels of LDL, HDL, and total cholesterol were not influenced by the drug (P=NS). Moxonidine decreases systolic and diastolic blood pressure by inhibiting central nervous sympathetic activity. This makes this new drug suitable for the treatment of human hypertension and possibly for other cardiovascular diseases with increased sympathetic nerve activity, ie, ischemic heart disease and heart failure.     

The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) may alter blood pressure through their inhibitory effects on prostaglandin biosynthesis. Such potential hypertensive effects of NSAIDs have not been adequately examined in the elderly, who are the largest group of NSAID users. METHODS: We performed a randomized, double-blind, two-period crossover trial of ibuprofen (1800 mg per day) vs placebo treatment in patients older than 60 years of age with hypertension controlled with hydrochlorothiazide. While continuing their usual thiazide dosage, subjects were randomized to a 4-week treatment period (ibuprofen or placebo) followed by a 2-week placebo wash-out period and a second 4-week treatment period with the alternative therapy. Supine and standing systolic and diastolic blood pressures were measured weekly. RESULTS: Of 25 randomized subjects, 22 completed the study protocol (mean age = 73 +/- 6.7 years). Supine systolic blood pressure and standing systolic blood pressure were increased significantly with ibuprofen treatment, compared with placebo. Mean supine systolic blood pressures were 143.8 +/- 21.0 and 139.6 +/- 15.9 mmHg on ibuprofen and placebo, respectively (p = .004). Mean standing systolic blood pressures were 148.1 +/- 19.9 and 143.4 +/- 17.9 mmHg on ibuprofen and placebo, respectively (p = .002). CONCLUSION: We conclude that 1800 mg per day of ibuprofen does induce a significant increase in systolic blood pressure in older hypertensive patients treated with hydrochlorothiazide. NSAID therapy may negatively impact the control of hypertension in elderly patients.     

Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10-year follow-up study

BACKGROUND: The aim of this study was to compare the risk conferred by white-coat versus sustained mild hypertension for the development of cardiovascular disease. METHODS AND RESULTS: Patients (n=479) who underwent 24-hour intra-arterial ambulatory blood pressure monitoring on the basis of a persistently elevated clinic systolic blood pressure of 140 to 180 mm Hg were followed up for the development of subsequent cardiovascular events during a 9.1+/-4. 2-year period. White-coat hypertension, defined as a clinic systolic blood pressure of 140 to 180 mm Hg associated with a 24-hour ambulatory systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg, was present in 126 patients, and the remainder had sustained mild hypertension. A subgroup of patients without complications underwent follow-up echocardiography and carotid ultrasound. White-coat hypertensives were younger (44+/-12 versus 52+/-10 years, respectively; P<0.001) and had a significantly lower incidence of cardiovascular events (1.32 versus 2.56 events per 100 patient-years, respectively; P<0.001) than sustained hypertensives. Multivariate analysis revealed age (P=0.002), sex (P=0.007), race (P=0.001), smoking (P=0.005), and the presence of white-coat hypertension (hazard ratio, 0.29; 95% CI, 0.09 to 0.90; P=0.04) to be independent predictors of subsequent cardiovascular events. Subgroup analysis in patients without complications revealed a lower incidence of left ventricular hypertrophy and lesser degrees of carotid hypertrophy in the white-coat group. CONCLUSIONS: These findings indicate a relatively benign outcome in white-coat hypertension compared with sustained mild hypertension.     

Diastolic function parameters and atrial arrhythmias in patients with arterial hypertension

OBJECTIVE: To investigate in patients with arterial hypertension (HT) the extent of left ventricular (LV) hypertrophy and diastolic function in relation to atrial arrhythmias. PATIENTS AND METHODS: In 112 hypertensive patients (40 women, 72 men; mean age 50 +/- 6.6 years) with a mean systolic blood pressure for the cohort of 170 +/- 5 mmHg, their first invasive coronary angiography was performed between July 1995 and October 1997 because of angina pectoris and/or an abnormal stress electrocardiogram. After excluding coronary heart disease LV dimensions and diastolic function were measured by echocardiography; in 59 of the 112 patients LV hypertrophy was demonstrated. In addition, long-term blood pressure monitoring, exercise and long-term electrocardiography, late-potential analysis and measurement of heart rate variability were undertaken. The control group consisted of 51 patients without arterial hypertension after exclusion of coronary heart disease. RESULTS: Even in the hypertensive patients without LV hypertrophy diastolic LV function and ergometric exercise capacity were reduced. The risk of LV arrhythmias was significantly higher in patients with LV hypertrophy than those without and in the control group, as measured by the complexity of atrial arrhythmias (P < 0.001), the incidence of abnormal late potentials (P < 0.001) and reduction in heart rate variability (29.3 +/- 5.3 ms vs 47.8 +/- 12.1 ms vs 60.7 +/- 6.6 ms; P < 0.001). There were similar results regarding severe complex atrial arrhythmias (38.5 vs 15.0 vs 0%; P < 0.001). The incidence of atrial arrhythmias correlated with the LV diameter (r = 0.68, P < 0.001), LV morphological dimensions and diastolic function (isovolumetric relaxation time r = 0.44, P < 0.001) and the ratio of early to late diastolic inflow (r = 0.46; P < 0.001). CONCLUSIONS: Hypertensive patients have a higher risk of atrial and ventricular arrhythmias, depending on the degree of LV hypertrophy. But atrial arrhythmias, in contrary to ventricular arrhythmias, are also closely related to abnormalities in LV diastolic function.     

Serum hepatocyte growth factor as a possible indicator of arteriosclerosis

OBJECTIVE: To investigate the possible involvement of hepatocyte growth factor in arteriosclerotic lesions, by studying the relationship between serum concentrations of hepatocyte growth factor and grades of retinal arteriosclerosis. METHODS: We measured the blood pressure, body mass index, serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, uric acid, total protein, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltranspeptidase, alkaline phosphatase, and hepatocyte growth factor, erythrocyte counts, hemoglobin concentration, and hematocrit levels of 112 adults. Serum concentrations of hepatocyte growth factor were measured by a specific enzyme-linked immunosorbent assay. For each subject, photographs of both optic fundi were taken, and the grade of arteriosclerotic changes in the retinal arteries was evaluated according to Scheie's classification. RESULTS: Individuals with more advanced grades of arteriosclerotic changes had higher serum hepatocyte growth factor values (grade 0, 0.056 +/- 0.004 ng/ml, n = 86; grade 1, 0.132 +/- 0.026 ng/ml, n = 17, P < 0.01, versus grade 0; grade 2-3, 0.271 +/- 0.023 ng/ml, n = 9, P < 0.01, versus grades 0 and 1). The serum hepatocyte growth factor concentrations were also correlated significantly to the serum uric acid concentrations (r = 0.230, P = 0.015) and erythrocyte counts (r = 0.299, P = 0.001), but not to the systolic and diastolic blood pressures, and other physical and humoral parameters. CONCLUSIONS: Serum hepatocyte growth factor levels are thought to indicate the presence or development of arteriosclerotic lesions and may be a useful biochemical parameter for estimating the development of systemic arteriosclerosis irrespective of blood pressure levels.     

Identification of a transforming growth factor alpha-like molecule in human seminal plasma

In a double-blind controlled trial, 91 middle-aged and elderly women with mild to moderate hypertension who were not on antihypertensive medication were randomly assigned to treatment with magnesium aspartate-HCl (20 mmol Mg/d) or placebo for 6 mo. Magnesium aspartate-HCl in the given dose was well-tolerated and was not associated with an increased frequency of diarrhea compared with placebo. At the end of the study, systolic blood pressure had fallen by 2.7 mm Hg (95% CI -1.2, 6.7; P = 0.18) and diastolic blood pressure by 3.4 mm Hg (1.3, 5.6; P = 0.003) more in the magnesium group than in the placebo group. Blood pressure response was not associated with baseline magnesium status, as measured by dietary magnesium intake and urinary magnesium excretion. Urinary magnesium excretion in the magnesium group increased by 50% during the intervention period. No changes were seen in other biochemical indexes, including serum concentrations of total and high-density-lipoprotein cholesterol. The findings suggest that oral supplementation with magnesium aspartate-HCl may lower blood pressure in subjects with mild to moderate hypertension.     

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.     

Age-related ocular blood flow changes

PURPOSE: Pulsatile ocular blood flow (POBF is influenced by well-known parameters, such as intraocular pressure (IOP), heart rate, scleral rigidity, blood pressure, and posture. Age is also likely to influence POBF strongly. The purpose of this study was to evaluate POBF in relation to age in normal subjects. METHODS: Relevant data were collected from a sample of 105 normal subjects, ranging in age from 10 to 80 years. To measure the effect of age on POBF, the subjects were divided into seven groups of 15 subjects each; the age range of each group spanned one decade, beginning with age 10. POBF and pulse amplitude (PA) were measured in sitting and supine positions and after suction cup application. RESULTS: Using linear regression analysis, there was a significant correlation between PA and age in the supine position (P = 0.012) and after suction cup application (P = 0.002); in the sitting position, there was a borderline level of statistical significance (P = 0.053). In the sitting position, POBF was 819 +/- 212 microliters/minute in the second decade and 630 +/- 194 microliters/minute in the eighth decade. In the sitting position and after suction cup application, but not in the supine position, a statistically significant correlation between POBF decrease and age was found with linear regression analysis (P < 0.001 and P = 0.004, respectively). Using multiple regression analysis, POBF values revealed a significant correlation with age (P < 0.001), but not with systolic and diastolic brachial pressure. Considering all the subjects, analysis of variance for repeated measures highlighted a significant decrease of POBF from the sitting to the supine position and associated with an IOP increase (P < 0.001) without significant changes of PA. After suction cup application, there was a significant reduction of both PA and POBF (P < 0.001). CONCLUSIONS: The data revealed that as age increased, PA decreased in all three series of measurements. POBF decreased with age, and in subjects older than 50 years, the decrease was more evident. These findings are especially noticeable after IOP increase with suction cup. It must be considered that the age-related value of POBF is a fundamental parameter to evaluate correctly the hemodynamic aspects of the pathologies affecting the eye.