Hyperhomocysteinemia in stable pediatric, adolescents, and young adult renal transplant recipients.

BACKGROUND: High total plasma homocysteine (tHcy) levels are accompanied by an increased risk for premature development of atherosclerosis and atherothrombosis. Adult renal transplant recipients have elevated tHcy levels. Corresponding data in pediatric, adolescent, and young adult renal transplant recipients are scarce. We investigated whether tHcy levels were elevated in stable renal transplant recipients who received kidney grafts before age 18. METHODS: This cross-sectional study was conducted during routine posttransplantation follow-up. Fasting tHcy levels, serum creatinine, and lipoprotein profile were measured in 38 clinically stable renal transplant recipients with different degrees of renal function. No patient was receiving B vitamin or folic acid supplementation. Estimated glomerular filtration rate (GFR) was assessed according to Schwartz's formula. All patients followed a triple-drug immunosuppressive regimen, with the exception of three patients (deflazacort and azathioprine). Forty-one apparently healthy subjects constituted the control group. tHcy levels were determined by fluorescence polarization immunoassay in an IMx analyzer. RESULTS: Mean tHcy levels in transplant recipients were significantly higher than in controls (16.8+/-8.7 micromol/L and 9.5+/-2.3 micromol/L, respectively; P<0.01). A significant positive correlation between tHcy and serum creatinine levels was observed for both transplant recipients (rS=0.70, P<0.01) and controls (rS=0.54, P<0.01). In transplant recipients, tHcy correlated negatively with estimated GFR (rS=[minus]0.47, P<0.05). Fasting tHcy levels in excess of 14.6 micromol/L (>95th percentile in controls) were present in 19 (50%) patients; 14 of these patients had an estimated GFR<60 ml/min per 1.73 m2. When the renal transplant recipients were analyzed by renal function, mean tHcy was significantly higher in patients with an estimated GFR<60 ml/min per 1.73 m2 compared with patients with an estimated GFR> or =60 ml/min per 1.73 m2 (20.5+/-9.9 vs. 13.2+/-5.8 micromol/L, P<0.01). Both groups were significantly different from controls (P<0.01). No relationship was found between tHcy level and either cumulative cyclosporine or cumulative methylprednisone doses. No differences were observed in tHcy levels or lipoprotein profile between patients who were receiving deflazacort and those on methylprednisone. CONCLUSIONS: Hyperhomocysteinemia in renal transplant recipients is a common condition. Testing for fasting tHcy level might be a useful tool to identify patients at increased risk for development of vascular disease.

Plasmatic homocysteine response to vitamin supplementation in elderly people.

Homocysteine (Hcy) increase is now widely accepted as a risk factor for vascular disease. The effects of folic acid (FA) and vitamins B12 and B6 in lowering Hcy have been extensively studied, but there is still little data on the response to FA dietary administration. Our purpose was to evaluate the impact of the diet and the degree of response to different doses of pharmacological FA supplementation. In a prospective, randomized, and simple blind study, 50 elderly subjects were given a 400-microg/day FA diet and were randomly assigned to one of the following treatments: Group I = placebo tablet; Group II = tablet containing 1-mg folic acid, 1-mg B12, and 25-mg B6; and Group III = tablet containing 2.5-mg folic acid and same B6 and B12 doses as Group II. Forty-four subjects completed the study, and their plasmas were evaluated. Hcy concentration significantly decreased even in patients with normal basal values, and there were no differences in the response between individuals receiving diet plus placebo and those receiving diet plus pharmacological supplementation. After the treatment, the mean decrease of plasmatic Hcy levels was 10.8 (9.4, 12.5) micromol/l, geometric mean [95% confidence interval (95% CI)], and particularly, the values for Group I were 10.6 (7.4, 14.8) micromol/l. In 31% of the subjects, the post-treatment Hcy levels were less than or = 5 micromol/l. These results show that a special diet, with or without pharmacological FA and B12 and B6 supplementation, significantly decreases the Hcy levels in elderly people. Therefore, a diet with high contents of FA might have an enormous impact on the morbidity and mortality of atherothrombosis.

Contribution of stroke volume to the change in pulse pressure pattern with age.

This study investigated the effect of age on pulse pressure and its underlying mechanisms in unmedicated hypertensive men with the same level of mean arterial pressure. We included 77 men 17 to 76 years old with daytime mean arterial pressure between 95 and 114 mm Hg. In the supine position, pulse pressure showed a significant widening in young (<30 years) and older (>/=60 years) patients. Pulse pressure decreased in parallel with stroke index from age >30 to 40 to 49 years. Upright posture, however, eliminated this difference through a larger orthostatic fall in stroke index and pulse pressure in the youngest patients. After age 50 years, pulse pressure exhibited a progressive widening despite the further age-related decrease in stroke index. Supine, upright, and 24-hour pulse pressure fitted a curvilinear correlation with age (r=0.55, 0.56, and 0.68, respectively, P<0.001), with a transition at age 50 years. Before age 50 years, 24-hour pulse pressure correlated positively with stroke volume (r=0.5, P<0.001) and negatively with arterial compliance (SV/PP ratio, r=-0.37, P<0.01). In contrast, in men >/=50 years old, 24-hour pulse pressure correlated negatively with the SV/PP ratio (r=-0.5; P<0.01), without significant influence of stroke volume. Thus, in hypertensive men, the age-related change in stroke volume significantly accounted for the change in clinic and ambulatory pulse pressure during young adulthood, but its contribution decreased after the fifth decade.

Lack of effective blood pressure control among an elder hypertensive population in Buenos Aires.

Our purpose was to determine the level of awareness, treatment, and control of hypertension in a population of subjects aged 65 or more. We studied a random sample from the national health care program in Buenos Aires. Letters were mailed to 1000 selected individuals. Among those eligible, 41.4% (n = 414) were enrolled. The mean age was 73.8 years and 68% were women. Prevalence of hypertension in our sample was 77.5% (n = 321). Awareness of hypertension was 60.7% (n = 195). Fifty-four percent (n = 173) of the hypertensive subjects were receiving pharmacologic treatment and only 18.5% (n = 32) of them were controlled. These results show that there is a low level of awareness, pharmacologic treatment, and control of hypertension in the studied elderly subjects.

Diastolic pressure underestimates age-related hemodynamic impairment.

It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the prevalence of diastolic hypertension toward a systolic pattern of hypertension with aging. Also, the results suggest that SBP, but not DBP, is a reliable indicator of the underlying hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly.

Hemodynamic effects of transdermal estradiol alone and combined with norethisterone acetate.

A 24 weeks, randomized, two-period, placebo controlled study was conducted to compare the effects of continuous transdermal 17 beta-estradiol replacement therapy (0.05 mg/day once a week) with placebo on systemic hemodynamics and blood pressure in postmenopausal women. Twenty-nine postmenopausal women (47-62 years) free of hormone replacement therapy were randomized in two groups; group 1 received estradiol patches for the first 12 weeks and placebo patches for the second, and group 2 received the same treatments in the reverse order. The effect of combined estradiol plus oral norethisterone acetate (NETA) 1 mg was also evaluated in the subset of women with intact uteri (n = 24). Crossover analysis showed that stroke volume and cardiac output were significantly higher (P < 0.05) and blood pressure was significantly lower (P < 0.05) with estradiol, irrespective of the order in which the treatments were administered. Although correlations between plasma estradiol levels during active treatment and hemodynamic changes were not significant, hemodynamic changes were significantly greater above 63 pg/ml than below this level (P < 0.05). Oral norethisterone acetate administration either during transdermal placebo or estradiol arms tended to modify systemic hemodynamics in the same direction than estradiol but the changes did not attained statistical significance. In summary compared with placebo, transdermal 17 beta-estradiol, replacement to postmenopausal women, increased cardiac output and decreased blood pressure. Although the average magnitude of changes was small, the results suggest that plasma estradiol levels could be a source of individual variability in the hemodynamic response. Oral NETA administration tended to enhance rather than reverse the estradiol-induced changes.

Relationship between systemic hemodynamics and ambulatory blood pressure level are sex dependent.

Sex-related differences in systemic hemodynamics were analyzed by means of cardiac index and systemic vascular resistance according to the level of daytime ambulatory blood pressure. In addition, we assessed the relations between ambulatory blood pressure measurements and systemic hemodynamics in male and female patients. We prospectively included 52 women and 53 men referred to our unit for evaluation of arterial hypertension. Women and men were grouped according to the level of daytime mean arterial pressure: < 110 or > or = 110 mm Hg. Patients underwent noninvasive evaluation of resting hemodynamics (impedance cardiography) and 24-hour ambulatory blood pressure monitoring. Compared with women men with lower daytime blood pressure had a 12% higher systemic vascular resistance index (P = NS) and a 14% lower cardiac index (P < .02), whereas men with higher daytime blood pressure had a 25% higher vascular resistance (P < .003) and a 21% lower cardiac index (P < .0004). Furthermore, in men systemic vascular resistance correlated positively with both daytime and nighttime systolic and diastolic blood pressures, whereas cardiac index correlated negatively only with daytime diastolic blood pressure. In contrast, women did not exhibit any significant correlation between hemodynamic parameters and ambulatory blood pressure measurements. In conclusion, sex-related differences in systemic hemodynamics were more pronounced in the group with higher daytime hypertension. The relations between systemic hemodynamics and ambulatory blood pressure level depended on the sex of the patient. In men a progressive circulatory impairment underlies the increasing level of ambulatory blood pressure, but this was not observed in women.

Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia?

Two women with preeclampsia treated unsuccessfully with alpha-methyldopa and magnesium sulfate became profoundly hypotensive when oral nifedipine was added. Blood pressure returned to previous levels without changes in fetal vitality. Awareness of this potentiation is important because nifedipine is being used increasingly in the treatment of pregnancy-related hypertension.