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Biomedical subjects

Carlos Calvo

Publications and source records attributed to Carlos Calvo.

At least 37 records · Page 2Linked to original sources

Effect of continuous positive airway pressure on ambulatory blood pressure in patients with obstructive sleep apnoea.

OBJECTIVES: Previous reports on the effects of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) on blood pressure has shown contradictory results. Accordingly, we have investigated the effects of CPAP on blood pressure and on the potential reversal of the diagnosis of hypertension in patients with OSA evaluated repeatedly by ambulatory blood pressure monitoring. METHODS: We studied 122 patients (104 men and 18 women), 55.1+/-10.5 years of age, with diagnosis of OSA corroborated by overnight polysomnography at the clinic. Among those patients, 83 were treated with CPAP after their first evaluation, while 39 remained without CPAP for the duration of the trial. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours, at baseline and after 2 and 4 months of intervention. RESULTS: There was a small, but not statistically significant, reduction in ambulatory blood pressure in patients treated with CPAP (0.7 and 1.5 mmHg in 24-h mean of systolic and diastolic blood pressure after 2 months of therapy; 2.0 and 2.3 mmHg after 4 months; P>0.239). The blood pressure reduction was very similar in patients with OSA followed for 4 months without CPAP (1.9 and 2.2 mmHg in 24-h mean of systolic and diastolic blood pressure, respectively; P=0.543). We found a high (77%) prevalence of hypertension among the patients participating in this study, although only 37% were receiving antihypertensive medication at the time of recruitment. The prevalence of hypertension was slightly but not significantly reduced to just 74% after 4 months of treatment with CPAP. CONCLUSIONS: The small reduction in blood pressure for consecutive profiles of ambulatory monitoring can probably be explained by the documented 'ABPM pressor effect' on patients using the ambulatory device for the first time. The high prevalence of hypertension among patients with OSA is not significantly reduced by treatment with CPAP. These results suggest that patients with OSA should always be properly evaluated for diagnosis of hypertension, and provided, if needed, with antihypertensive treatment apart from the recommended CPAP.

Blood Pressure↗

Particulate silicone for vocal fold augmentation: morphometric evaluation in a rabbit model.

To study the augmentation of the paralyzed vocal fold in response to the injection of particulate plastics in a rabbit model, we performed a prospective, experimental, and controlled study in 45 New Zealand rabbits with surgical vocal fold paralysis. We compared a control group (acute unilateral recurrent nerve section) with a group that underwent polytetrafluoroethylene (PTFE) injection and with another group that underwent polydimethylsiloxane (PDMS) injection. Equal volumes of implant material were injected. The animals were killed either 6 weeks or 6 months after intervention and compared by histomorphology using a digital measuring system. The injection sites showed a substantial foreign body giant cell reaction against the PDMS and PTFE, surrounded by a light, fibrous stroma. No differences in the frequency of displacement or disaggregation of implants were observed. No extrusion to the laryngeal lumen, signs of migration outside the larynx, or malignant changes were seen. No differences were found in the length of the vocal fold between the PDMS group and the PTFE group. The vocal fold was thicker in the PDMS group than in the PTFE group, but a statistically significant difference was found only for the anterior and middle thirds at 6 weeks. In the PDMS sample, the thicknesses were similar in the 6-week and 6-month subgroups. The group with injection of PDMS yielded histologic images compatible with greater and more stable medialization than did the group with injection of PTFE.

Animals↗

Polydimethylsiloxane versus polytetrafluoroethylene for vocal fold medialization: histologic evaluation in a rabbit model.

The objective is to study the tissue reaction of the paralyzed vocal cord in response to the injection of particulate plastics in a rabbit model. Forty-five New Zealand rabbits with surgical vocal-fold paralysis were used in the study. Histologic reactions of the larynx and the regional lymph nodes were analyzed by a single blinded pathologist at 6 weeks and 6 months after a vocal-cord injection of Teflon or of silicone elastomer. Macroscopic studies of the liver, lungs, spleen, kidney, and brain were performed. The histological study showed a greater proportion of chronic granulomatous inflammation in animals injected with silicone than in those injected with Teflon. The immunohistochemical study showed a higher degree of phagocytosis of Teflon particles than of the silicone particles. The silicone group presented a more severe fibrous reaction than the Teflon group, but the difference was not significant. No migration particles were found. It is concluded that silicone, having a greater viscosity than Teflon because of the size of its particles, induces more fibrosis and a larger proportion of foreign giant cells in the host. Due to this histological reaction, silicone particles present greater anchorage and stability.

Animals↗

Seasonal variation of fibrinogen in dipper and nondipper hypertensive patients.

BACKGROUND: A seasonal variation with higher values in winter has been previously reported in plasma fibrinogen, a recognized marker of the potential risk of myocardial infarction and stroke. The lack of nocturnal decline in blood pressure has also been associated with an increase in cardiovascular events. Accordingly, we have compared the yearly variation of plasma fibrinogen in dipper and nondipper hypertensive patients. METHODS AND RESULTS: We studied 1006 stage 1 to 2 hypertensive patients (482 men and 524 women, 53.0+/-13.4 years of age). Blood pressure was measured every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-minute intervals with a wrist actigraph. A blood sample was collected on the same day before starting blood pressure monitoring. The circannual variation of fibrinogen was established for all patients as well as for subgroups of dippers and nondippers (n=513; nocturnal blood pressure decline <10%) by multiple-component analysis. For the whole group of patients, fibrinogen was characterized by a highly significant seasonal variation (P<0.001) with a mean value of 318 mg/dL, double circannual amplitude (extent of predictable change along the year) of 40 mg/dL, and time of peak value in February. Throughout the year, the nondippers showed higher plasma fibrinogen levels than did the dippers (P<0.001). CONCLUSIONS: The elevated plasma fibrinogen levels in nondipper patients appear to be directly related to their increased risk in vascular events, which are more prominent during the late winter months.

Adult↗

Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects.

This study investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects (30 men and 60 women), 49.0+/-14.3 (mean+/-SD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan (P<0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; P>0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% (P<0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation.

Adult↗

[Seasonal variation in plasma fibrinogen in dipper and non-dipper patients with mild-moderate essential hypertension].

BACKGROUND AND OBJECTIVE: Increased plasma fibrinogen is recognized as a significant parameter for assessing the potential risk of myocardial infarction and stroke. A seasonal variation has been reported for plasma fibrinogen, with highest values occurring in the coldest months of the year. On the other hand, the lack of nocturnal decline in blood pressure has been associated with an increase in cardiovascular events. Accordingly, we have quantified the yearly variation in plasma fibrinogen in hypertensive patients classified according to their nocturnal decline in blood pressure. PATIENTS AND METHOD: We studied 577 mild-to-moderate hypertensive patients (254 men), 53.8 13.8 years of age. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-min intervals with a wrist actigraph. A complete blood test was performed on the same day before starting blood pressure monitoring. The circannual variation of plasma fibrinogen was established for all patients as well as for subgroups of dippers (n = 287) and non-dippers (n = 290; patients with a nocturnal blood pressure decline < 10% of the diurnal mean) by multiple-component analysis. RESULTS: For the whole group of hypertensive patients, plasma fibrinogen was characterized by a highly significant seasonal variation (p < 0.001), with a mean value of 324 mg/dl, double circannual amplitude (i.e, extent of predictable change along the year) of 75 mg/dl, and time of peak value on the first week of March. This circannual variation can be best represented by a model that includes components with periods of 12 and 6 months. The same model also characterized dippers as well as non-dippers, analyzed separately. Non-dippers showed higher plasma fibrinogen throughout the whole year as compared to dippers (p = 0.002). CONCLUSIONS: The elevation of plasma fibrinogen in non-dipper patients as compared to dippers could support the association between the lack of nocturnal decline in blood pressure with an increase in cardiovascular events, since the circannual variation in fibrinogen is timely correlated with the reported yearly variation in coronary events.

Adult↗

[Administration-time dependent effects of acetyl-salicylic acid on blood pressure in patients with mild essential hypertension].

BACKGROUND AND OBJECTIVES: Previous studies on the potential influence of aspirin (AAS) on blood pressure have not taken in consideration the chronopharmacologic effects of non-steroidal antiinflammatory drugs. This pilot study investigated the effects of AAS on blood pressure in hypertensive patients under no antihypertensive treatment who received AAS at different day times according to their rest-activity cycle. PATIENTS AND METHOD: We studied 64 untreated patients with mild hypertension (24 men), 43.5 (12.0) (mean [SD]) years of age, randomly divided in 3 groups: group 1, non-pharmacological hygienic-dietetic recommendations; group 2, the same recommendations plus AAS (100 mg/day) on awakening, and group 3, the same recommendations plus AAS (100 mg/day) before bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of blood pressure in each group was established by population multiple-component analysis. Circadian parameters obtained for each group of patients before and after the intervention were compared with a nonparametric paired test. RESULTS: After 3 months of non-pharmacological intervention, there was a small and non-significant reduction of blood pressure (< 1.5 mmHg; p = 0.28). There was no change in blood pressure when AAS was given on awakening (p = 0.21). A highly significant blood pressure reduction was, however, observed in patients who received AAS before bedtime (decrease of 7 and 5 mmHg in systolic and diastolic blood pressure, respectively; p = 0.006). CONCLUSIONS: Our results indicate a statistically significant time-dependent administration effect of low-dose AAS on blood pressure in untreated patients with mild hypertension. This effect reinforces the need to quantify and control AAS effects in patients using this agent in combination with antihypertensive agents.

Anti-Inflammatory Agents, Non-Steroidal↗

Administration time-dependent effects of aspirin on blood pressure in untreated hypertensive patients.

Previous studies on the potential influence of aspirin on blood pressure have not taken into consideration the chronopharmacological effects of nonsteroidal anti-inflammatory drugs. This pilot study investigates the effects of aspirin on blood pressure in untreated hypertensive patients who received aspirin at different times of the day according to their rest-activity cycle. We studied 100 untreated patients with mild hypertension (34 men and 66 women), 42.5+/-11.6 (mean+/-SD) years of age, randomly divided into 3 groups: nonpharmacological hygienic-dietary recommendations; the same recommendations and aspirin (100 mg/d) on awakening; or the same recommendations and aspirin before bedtime. Blood pressure was measured every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of blood pressure in each group was established by population multiple-component analysis. After 3 months of nonpharmacological intervention, there was a small, nonsignificant reduction of blood pressure (<1.1 mm Hg; P>0.341). There was no change in blood pressure when aspirin was given on awakening (P=0.229). A highly significant blood pressure reduction was, however, observed in the patients who received aspirin before bedtime (decrease of 6 and 4 mm Hg in systolic and diastolic blood pressure, respectively; P<0.001). Results indicate a statistically significant administration time-dependent effect of low-dose aspirin on blood pressure in untreated patients with mild hypertension. The influence of aspirin on blood pressure demonstrated in this study indicates the need to quantify and control for aspirin effects in patients using this drug in combination with antihypertensive medication.

Adult↗

Once-daily fixed-combination irbesartan 300 mg/ hydrochlorothiazide 25 mg and circadian blood pressure profile in patients with essential hypertension.

BACKGROUND: More than 60% of patients with hypertension included in morbidity and mortality trials needed >or=2 drugs to achieve a substantial, sustained reduction in blood pressure. Tolerable combinations using higher doses of antihypertensive drugs are frequently required to control blood pressure. OBJECTIVE: The goal of this study was to assess the effect of a once-daily fixed combination of irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg on the circadian blood pressure profile in patients with essential hypertension that was not controlled with full-dose single therapy or low-dose combined therapy. METHODS: Study patients were recruited consecutively from the outpatient hypertension clinics of 3 university hospitals in Spain. After a 1-week washout period, patients with a mean daytime blood pressure >135/85 mm Hg were treated with irbesartan 300 mg/HCTZ 25 mg once daily for 12 weeks. Twenty-four-hour ambulatory blood pressure monitoring was performed at the end of the washout period and during the last week of treatment. RESULTS: Fifty-seven patients with essential hypertension (28 men, 29 women) were enrolled; their mean (SD) age was 60.4 (7.2) years (range, 45-78 years). After treatment, a significant reduction in both clinic and ambulatory mean (SD) blood pressure values was observed in the whole group of 57 patients (from 146.0 [11.0] mm Hg to 123.3 [13.3] mm Hg, P < 0.001 for 24-hour systolic blood pressure [SBP]; from 89.9 [8.2] mm Hg to 76.5 [9.4] mm Hg, P < 0.001 for 24-hour diastolic blood pressure [DBP]. The mean lowering of ambulatory SBP and DBP at peak was 25.2 (14.5) mm Hg and 14.7 (9.5) mm Hg, respectively, and at trough, 22.3 (18.3) mm Hg and 12.3 (10.9) mm Hg. The trough-to-peak ratio of the group was 0.92 for SBP (0.97 in responders) and 0.84 for DBP (0.89 in responders). The smoothness index, calculated as the mean of all individual values, was 1.7 (1.0) for SBP (1.8 [0.9] in responders) and 1.3 (0.8) for DBP (1.5 [0.6] in responders). Seven side effects in 6 patients were reported. No metabolic changes were observed, and no patient discontinued the study because of treatment-related adverse effects. CONCLUSIONS: The fixed combination of irbesartan 300 mg/HCTZ 25 administered once daily produced a crude meaningful effect in reducing 24-hour blood pressure and was well tolerated. The circadian profile was preserved, as shown by trough-to-peak ratios and smoothness index values for both SBP and DBP.

Aged↗

Verapamil reverts acute renal functional impairment induced by angiotensin II converting enzyme inhibitors.

Angiotensin converting enzyme inhibitors (ACEI) reduce blood pressure (BP) and provide end-organ protection, but may induce renal function deterioration. In these cases, serum creatinine (SCr) can be normalized by ACEI withdrawn. In some patients, it could be desirable to maintain the ACEI for the protection of the kidney and heart. The objective of the study was to evaluate the effect of Verapamil (V) on renal function added to patients with elevated SCr due to ACEI treatment. In 46 hypertensive patients without previous renal failure, in which ACEI treatment induced an acute increase in SCr (> or = 20% or 0.5 mg/dL), ACEI treatment was maintained and 180 mg/day of V was added for 12 weeks. Those patients showing further SCr increase or no BP control at four weeks were withdrawn. Patients under BP control were moved on the combination V 180 + Trandolapril 2 mg/day for eight weeks more. SCr decreased from 136 +/- 49 micromol/L at baseline to 126 +/- 49 at 12 weeks after adding V (p < 0.001) and to 111 +/- 31 micromol/L at 20 weeks (p < 0.01). Creatinine clearance increased from 62 +/- 22 mL/min at baseline to 68 +/- 28 after 12 weeks of V (p < 0.001). This article demonstrates than in patients with acute renal function impairment secondary to ACEI treatment, the addition of 180 mg/day of verapamil to ACEI reverses SCr towards previous values.

Acute Kidney Injury↗

The 'ABPM effect' gradually decreases but does not disappear in successive sessions of ambulatory monitoring.

OBJECTIVES: Previous results have indicated that ambulatory monitoring provides a pressor effect on patients using the device for the first time, but not on successive sessions of monitoring. Our objective was to validate and quantify the extent and duration of this pressor effect in hypertensive patients repeatedly evaluated every few months. METHODS: We studied 823 mild-to-moderate hypertensive subjects (347 men), 53.4 +/- 14.1 years of age. Blood pressure was measured at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours, and physical activity was simultaneously evaluated every minute with a wrist actigraph. Forty per cent of the patients were evaluated twice or more. RESULTS: In patients evaluated for the first time, results indicated a highly statistically significant (P < 0.001) reduction during the second day of monitoring as compared to the first in the diurnal mean of systolic and diastolic blood pressure, but not in heart rate or physical activity. This pressor effect remained statistically significant for the first 10 h of monitoring, independent of gender, day of the week of monitoring, or number of antihypertensive drugs used by the patients. The nocturnal mean of blood pressure was, however, similar between both days of sampling. This 'ambulatory monitoring effect' was diminished, although not eliminated, in extent and duration for successive sessions of ambulatory monitoring. CONCLUSIONS: Ambulatory monitoring for 48 h revealed a statistically significant pressor response that could mostly reflect a novelty effect in the use of the monitoring device. This effect has marked implications in both research and clinical daily practice for a proper diagnosis of hypertension and evaluation of treatment efficacy by the use of ambulatory monitoring.

Adolescent↗

Autologous elastic cartilage for laryngoplasty: histologic evaluation in a rabbit model.

A wide range of materials have been used to achieve medialization of the paralyzed vocal fold. Recently, medialization techniques using autologous cartilage have been described, but little information is available on cartilage integration and viability in this situation. In this prospective, experimental, controlled study, right vocal fold paralysis was surgically induced in 30 New Zealand rabbits. An autologous auricular cartilage transplant was inserted in the vocal fold in 15 animals. In the control group, only the laryngeal nerve was sectioned. Each group was divided into two groups with follow-ups of 6 weeks and 6 months, respectively. Histologic studies revealed no inflammatory reaction against the cartilage transplants. There were no differences in the transplant surfaces in the 6-week and 6-month groups. The results show tissue integration and a low level of initial transplant resorption that stabilizes with time. Autologous auricular cartilage appears to be an appropriate material for type I thyroplasty procedures because of the low absorption rate.

Animals↗

Evaluation of the extent and duration of the "ABPM effect" in hypertensive patients.

OBJECTIVES: The goal of this study was to test and quantify the extent and duration over time of a possible pressor effect due to ambulatory monitoring. BACKGROUND: The use of ambulatory blood pressure monitoring has provided a method of blood pressure (BP) assessment that compensates for some of the limitations of office values. While a "white-coat" pressor effect on conventional measurements has been defined and frequently used for the improved evaluation of hypertensive patients, there has not been clear indication that the ambulatory technique could also influence BP. METHODS: We studied 538 mild-to-moderate hypertensive patients (233 men), 54.2 +/- 14.2 (mean +/- SD) years of age. Blood pressure and heart rate were measured at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours, and physical activity was simultaneously evaluated at 1-min intervals with a wrist actigraph. One-third of the patients were evaluated twice or more times. RESULTS: In both treated and untreated hypertensive patients evaluated for the first time, results indicate a statistically significant (p < 0.001) reduction during the second day of monitoring as compared with the first in the diurnal mean of systolic and diastolic BP, but not in heart rate or physical activity. This pressor effect remains statistically significant for the first 6 h to 8 h of monitoring independently of gender, days of the week of monitoring or number of antihypertensive drugs used by the treated patients. The nocturnal mean of BP was, however, similar between both days of sampling. This "ambulatory monitoring effect" was not observed when the patients were evaluated after the same sampling scheme for the second or successive times three months apart. CONCLUSIONS: Ambulatory monitoring for 48 consecutive hours reveals a statistically significant pressor response that could reflect a novelty effect in the use of the monitoring device for the first time. This effect has marked implications in both research and clinical daily practice for a proper diagnosis of hypertension and evaluation of treatment efficacy by the use of ambulatory monitoring.

Adult↗

[Blood pressure differences between consecutive days of ambulatory monitoring in hypertensive patients: the ABPM effect].

BACKGROUND: Ambulatory blood pressure monitoring is a method of blood pressure assessment that compensates for some of the limitations of office values. While a white-coat pressor effect on conventional determination has been defined and frequently used for the improved evaluation of hypertensive patients, there is no evidence that the ambulatory technique could also influence blood pressure. PATIENTS AND METHOD: Aimed at testing and quantifying the extent and duration over time of a possible pressor effect due to ambulatory monitoring, we studied 387 mild-to-moderate hypertensive patients (160 men), aged 54.2 (14.3) (mean [SD]). Blood pressure and heart rate were measured at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours, and physical activity was simultaneously evaluated at 1-min intervals by means of a wrist actigraph. One third of patients were evaluated twice or more times. RESULTS: In hypertensive patients who were evaluated for the first time, results indicate a highly significant (p < 0.001) reduction, in the second day of monitoring as compared to the first, in the diurnal mean of systolic and diastolic blood pressure, but not in heart rate or physical activity. This pressor effect remains significant for at least the first 5 hours of monitoring. The nocturnal mean of blood pressure was, however, similar in the two days of sampling. This ambulatory monitoring effect could not be observed when patients were evaluated following the same sampling scheme at the second or further times. CONCLUSIONS: Ambulatory monitoring for 48 consecutive hours reveals a statistically significant pressor response that could reflect a novelty effect in the use of the monitoring device for the first time. This effect has notable implications in both research and clinical daily practice, both for proper diagnosis of hypertension and evaluation of treatment efficacy.

Adult↗

A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL).

BACKGROUND: When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200) with essential hypertension. OBJECTIVE: This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated. METHODS: This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90-109 mm Hg or systolic BP [SBP] 140-179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP > or = 85 mm Hg, as measured by ABPM between 10 AM and 8 PM, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders, in dependent of clinic values. RESULTS: A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was approximately 52.0% female and 48.0% male, with a mean ( +/- SD) age of 52.7 +/- 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 +/- 8.8 mm Hg irbesartan vs 12.4 +/- 7.4 mm Hg enalapril; SBP, 19.0 +/- 14.1 mm Hg vs 17.5 +/- 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 +/- 8.5 mm Hg vs 8.8 +/- 8.5 mm Hg: SBP, 14.7 +/- 14.7 mm Hg vs 12.6 +/- 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%). CONCLUSIONS: As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.

Adult↗

Sequential estrogen-progestin replacement therapy in healthy postmenopausal women: effects on cholesterol efflux capacity and key proteins regulating high-density lipoprotein levels.

Thirty healthy postmenopausal women were randomized into 2 groups that received a sequential combined hormone-replacement therapy (HRT) (n = 18; conjugated equine estrogen 0.625 mg/d for 28 days and 5 mg of medroxyprogesterone acetate during the last 14 days) or placebo (n = 12). Plasma samples were collected before and during treatment (days 0, 15, 43, 71). High-density lipoprotein (HDL) lipid content, lipoprotein (Lp)A-I and LpA-I:LpA-II concentration, lecithin:cholesterol acyl transferase activity (LCAT), phospholipid transfer protein (PLTP) activity, and the plasma capacity to carry out cholesterol efflux from Fu5AH cells were measured. Most significant changes were found within the first 15 days after HRT. After 71 days of HRT, we found an increase in LpA-I lipoparticles (27%) and the following HDL lipids: phospholipids (21%), triglycerides (45%), and free cholesterol (43%), as well as an increase in cholesterol efflux (12.5%). PLTP activity, on the other hand, decreased 21% after 71 days of treatment. No significant changes in LCAT activity, HDL-cholesterol ester or LpA-I:LpA-II particles were found. Positive correlation between cholesterol efflux and the variables LpA-I and HDL-phospholipids were observed. PLTP was negatively correlated with apolipoprotein (apo) A-I, LpA-I, and LpA-I:LpA-II. In summary, our study, performed during 3 hormonal cycles, shows that HRT not only modifies HDL-cholesterol level, but also its lipid composition and HDL lipoparticle distribution. HRT enhances the plasma capacity to carry out cholesterol efflux from the Fu5AH system and decreases the activity of PLTP, a key protein regulating HDL levels. Considering the protocol sampling, these results represent mainly the estrogenic effect of HRT.

Cholesterol, HDL↗

Modeling the circadian variability of ambulatorily monitored blood pressure by multiple-component analysis.

The use of a set of new end points derived from ambulatory blood pressure monitoring (ABPM), in addition to the blood pressure (BP) values themselves, has been advocated to improve the sensitivity and specificity in diagnosing hypertension and to evaluate a person's response to treatment. An adequate estimation of rhythmic parameters depends, however, on the ability to describe properly the circadian pattern of BP variability. The purpose of this study was to identify a simple model that could characterize sufficiently well the circadian pattern of BP in normotensive healthy volunteers sampled by ambulatory monitoring. We studied 278 clinically healthy Spanish adults (184 men), 22.7 +/- 3.3 yr of age, without medical history of hypertension and mean BP from ambulatory profiles always below 135/85 mmHg for systolic/diastolic BP, who underwent sequential ABPM providing a total of 1115 series of BPs and heart rates (HRs), sampled on each occasion at 0.5h intervals for 48 h. Subjects were assessed while adhering to their usual diurnal activity and nocturnal sleep routine, without restrictions but avoiding the use of medication. The circadian rhythm in BP and HR for each subject was established by multiple-component analysis. A statistically significant 24h component is documented for 97% of the BP profiles, with a significant second (12h) harmonic documented in 65% of the profiles. Other ultradian harmonic components were significant in less than 20% of the profiles. A statistically significant increase in the coefficient of determination (percent of overall variability explained by the function fitted to the data) was only obtained after including the periods of 24 and 12 h for BP, and periods of 24, 12, and 6 h for HR in the model components. Although other ultradian components can be demonstrated as statistically significant in a small percent of subjects, a rather simple model including only the two first harmonics of the 24h period describes sufficiently well, at the specified sampling rate, the circadian pattern of BP in normotensive subjects. Departure from this model could characterize overt pathology, as recently demonstrated in the diagnosis of preeclampsia.

Adult↗

An ELISA procedure for human Lp(a) quantitation using monoclonal antibodies.

The present study describes a monoclonal antibody-based enzyme immunoassay (ELISA) for the quantitation of lipoprotein(a), Lp(a), in human plasma. Two antibodies to Lp(a), 2F4E7 and 8G12G7, were produced and characterized as specific and high affinity antibodies against Lp(a). A reference control serum was utilized to prepare the standard curve in a Lp(a) concentration range from 0.015 to 0.5 ug/ml. A biotinylated monoclonal antibody against apoB-LDL was used as the second antibody. The comparison of the standardized ELISA using mAb 2F4E7 with an ELISA using a characterized mAb against Lp(a) (clone KO9) as capture antibody showed that the Lp(a) concentration of two standard sera was similar with both assays. Furthermore, when compared with an electroimmunoassay kit, similar Lp(a) concentrations for the standard were also obtained.

Animals↗