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M.478 Prevalence of non-dipper blood pressure pattern in elderly patients with essential hypertension as a function of the circadian time of antihypertensive therapy
Miscellaneous therapeutic approach allows reducing the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk.
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PREVALENCE OF NON-DIPPER BLOOD PRESSURE PATTERN IN ELDERLY PATIENTS WITH ESSENTIAL HYPERTENSION AS A FUNCTION OF THE CIRCADIAN TIME OF ANTIHYPERTENSIVE THERAPY
Caparevic
111
on hypertensive patients with and without DM evaluated by 48-hour ABPM and with nocturnal BP mean calculated individually according to actual resting time determined by actigraphy, indicates the high prevalence of an altered ch'cadian BP pattern in DM. The high prevalence of risers among patients with DM indicates the need to establish a proper chronotherapeutic antihypertensive scheme that could allow not only to reduce BP but also to modify the altered ch'cadian profile into a dipper pattern with a lower cardiovascular risk.
C. Calvo, R. Herrnida, D. Ayala, M. Dominguez, M. Covelo, J. Lopez.
Hypertension and Vascular Risk Unit, Hospital CI nico Universitario, Santiago, Bioengineering & Chronobiology Labs., Univ. Vigo, Vigo, Spain Recent results indicated that non-dipping in treated hypertensive patients is in part related to the absence of 24-hour therapeutic coverage [J Hypel: tens. 2002;20:1097-1104]. In the elderly, as compared to younger patients, the day/night blood pressure (BP) ratio is diminished due to an increase in nocturnal BP. Accordingly, we studied the impact of antihypertensive treatment and the time of therapy on the cfl'cadian pattern of BP in elderly patients with essential hypertension. We studied 682 elderly patients (age >65 years) with grade 1-2 essential hypertension (295 men), 70.9-4-4.7 years of age. Among them, 175 patients (77 men) did not receive antihypertensive medication before nor during the study. Among the treated patients, 64% leceived all theft" medication upon awakening. BP was measured at 20-rain intervals fi'om 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. In untreated patients, 66.3% were non-dippers (nocturnal BP decline < 10% of the diurnal mean). In treated as compared to untreated patients, BP was highly reduced during diurnally active hours, but not during nocturnal sleep, in the absence of significant changes in activity. The percentage of non-dippers among treated patients was increased up to 69.4%. As a function of the cfl'cadian time of treatment, 81.5% of the patients with all drugs on awakening were non-dippers. This percentage was significantly 1educed to 49.4% in patients who received one antihypertensive drug before bedtime (P<0.001). Antihypertensive therapy, mostly given exclusively upon awakening, significantly modifies the cfl'cadian pattern of BP. In the elderly, pharrnacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient, as a function of the therapeutic coverage of the drugs and the baseline cfl'cadian BP profile of the patient. This chronopharrnacology therapeutic approach allows reducing the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk.
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PREVALENCE OF AN ALTERED NOCTURNAL DECLINE OF BLOOD PRESSURE IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES
C. Calvo, R. Herrnida, D. Ayala, M. Dominguez, M. Covelo, J. Lopez.
Hypertension and Vascular Risk Unit, Hospital CI nico Universitario, Santiago, Bioengineering & Chronobiology Labs., Univ. Vigo, Vigo, Spain The plevalence of a non-dipping pattern in type 2 diabetes mellitus (DM) is highly variable among different studies. Recent results have indicated that non-dipping in tleated hypertensive patients is markedly related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097-1104]. Accordingly, we have evaluated the prevalence of non-dipping in treated and untreated hypertensive patients with and without DM. We studied 234 hypertensive patients with DM (129 men), 59.8-4-11.3 years of age, and 1184 patients with grade 1-2 essential hypertension (512 men), 52.1-4-13.9 years of age. 88 patients with DM and 679 hypertensive controls were untreated at the time of the study. Blood pressure (BP) was measured by ambulatory monitoring (ABPM) at 20-rain intervals fi'om 07:00 to 23:00 hours and at 30-rain intervals at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-min intervals by wrist actigraphy. Diurnal and nocturnal means of BP obtained according to individual resting time determined by actigraphy were used to classify each patient as dipper o1" non-dipper (nocturnal BP decline < 10%). Among untleated patients without DM, 40.4% wele non-dippers. This percentage was significantly increased to 56.6% among treated patients. In DM, 65% of the untreated patients and 77% of the treated patients were non-dippers. More importantly, the percentage of risers (patients with nocturnal BP mean above the diurnal mean) increased fi'om 3.7% in untreated controls to 17.1% in untreated patients with DM, and fi'om 11.9% among treated hypertensive patients to a very high 28.1% among treated patients with DM. Results fi'om this study
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EFFECTS OF ATORVASTATIN ON AMBULATORY BLOOD PRESSURE IN HYPERLIPIDEMIC PATIENTS W I T H UNTREATED MILD HYPERTENSION
C. Calvo, R. Herrnida, D. Ayala, J. Lopez, M. Dominguez, M. Covelo.
Hypertension and Vascular Risk Unit, Hospital CI nico Universitario, Santiago, Bioengineering & Chronobiology Labs., Univ. Vigo, Vigo, Spain Endothelium-dependent vasodilation is abnormal in hypercholesterolemic patients, while hypolipidemic therapy has been shown to improve endothelium dysfunction. Recent results have shown that atorvastatin, a HMG-CoA reductase inhibitor, conU'ibutes to a change in arterial stiffness independent of blood pressure (BP) level. Thus, some previous results have suggested that atorvastatin could have an added capacity to reduce BE Accordingly, we investigated the potential effects of atorvastatin on BP, independently of its effects on lipids, in patients with untreated mild hypertension who were evaluated by 48-hour ambulatory BP monitoring (ABPM). We studied 18 patients (6 men), 57.5-t- 10.9 years of age, with primary hypercholesterolemia (plasma cholesterol 250-300 mg/dl and triglycerides <400 mg/dl). Patients had mild hypertension diagnosed by the average of 6 conventional BP meastu'ements (> 140 or 90 mm Hg for systolic o1"diastolic BP) and corroborated fi'om the results of ABPM. They did not receive any antihypertensive medication neither before nor during the dtu'ation of this trial. Patients received atorvastatin (10 mg/day) for 3 months. BP was measured at 20-min intervals fi'om 07:00 to 23:00 hotu's and at 30-min intervals at night for 48 consecutive hotu's before and after 3 months of treatment with atorvastatin. Physical activity was simultaneously evaluated at 1-min intervals by wrist actigraphy. Cfl'cadian parameters of BP obtained for the patients before and after intervention by population multiple-components analysis were compared with a pahed nonparametric test. Results indicate highly statistically significant reductions in BP after 3 months of therapy with atorvastatin (7.2 and 4.6 mm Hg in the 24-hour mean of systolic and diastolic BP, respectively; p<0.001 in both cases). Despite this highly significant effect on BP, heart rate remained unchanged (declease on 0.7 beats/minute in 24-hour mean after therapy, P=0.576). Apart fi'om its previously demonstrated hypolipidemic effects, atorvastatin significantly reduces both systolic and diastolic BP, without affecting heart rate, in hypercholesterolemic patients with mild hypertension. This effect on BP could be mediated through the improvement of the endothelium dysfunction that characterizes these patients.
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OXIDIZED LDL IN MIDDLE-AGED TYPE 2 DIABETES PATIENTS WITHOUT CORONARY HEART DISEASE
Z. Caparevic, D. Begovic, D. Petrovic, S. Spasic, R. Cvetkovic. CHC Dr D. Misovic, University of Medicine, Department of Endocrinology, Belgrade, Serbia and Montenegro Background and Aims: Subjects with high plasma oxidized LDL (oxLDL) is at increased risk for development of coronary heart disease (CHD). The aim of this study was to estimate relations between ox LDL and other lipid risk factors for CHD in middle-aged subjects without CHD. Materials and Methods: Investigation was perforrned in 30 well controled diabetics type 2 patients (HbAlc<6.5%; FBG<5.5mmol/1) without CHD (group A) and in 27 hypercholesterolemic healthy middle-aged subjects (52,33-t-3,9 year (group B). Triglycerides, total-C and HDL-C were measmed by enzymatic methods. LDL-C was calculated using the Fliedewald fommla. Ox-LDL was detemained by ELISA (Mercodia AB, Uppsala, Sweden) Results: We found that ox LDL was slightly, but not significantly higher in group A than in group B (152.67-t-48.15 vs 126.91-t-43.46 IU/1; p>0.05). Conventional lipid profile (total Ch, LDL-Ch, HDL-Ch and Tg) as well as LDL/HDL ratio and Tg/HDL ratio, were similar between groups A and B. In group A we found significant colrelations between ox LDL with Tg (r=0.606: p=0.009), LDL/HDL ratio (r=0.553; p=0.02) and Tg/HDL (r=0.550; p=0.02). In group B we found that ox LDL significantly con'elated with total-Ch (r=0.747; p<0.005) and LDL-Ch (r=0.646; p=0.02).
74th EAS Congress, 17-20 April 2004, Seville, Spain
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PREVALENCE OF NON-DIPPER BLOOD PRESSURE PATTERN IN ELDERLY PATIENTS WITH ESSENTIAL HYPERTENSION AS A FUNCTION OF THE CIRCADIAN TIME OF ANTIHYPERTENSIVE THERAPY
Caparevic
111
on hypertensive patients with and without DM evaluated by 48-hour ABPM and with nocturnal BP mean calculated individually according to actual resting time determined by actigraphy, indicates the high prevalence of an altered ch'cadian BP pattern in DM. The high prevalence of risers among patients with DM indicates the need to establish a proper chronotherapeutic antihypertensive scheme that could allow not only to reduce BP but also to modify the altered ch'cadian profile into a dipper pattern with a lower cardiovascular risk.
C. Calvo, R. Herrnida, D. Ayala, M. Dominguez, M. Covelo, J. Lopez.
Hypertension and Vascular Risk Unit, Hospital CI nico Universitario, Santiago, Bioengineering & Chronobiology Labs., Univ. Vigo, Vigo, Spain Recent results indicated that non-dipping in treated hypertensive patients is in part related to the absence of 24-hour therapeutic coverage [J Hypel: tens. 2002;20:1097-1104]. In the elderly, as compared to younger patients, the day/night blood pressure (BP) ratio is diminished due to an increase in nocturnal BP. Accordingly, we studied the impact of antihypertensive treatment and the time of therapy on the cfl'cadian pattern of BP in elderly patients with essential hypertension. We studied 682 elderly patients (age >65 years) with grade 1-2 essential hypertension (295 men), 70.9-4-4.7 years of age. Among them, 175 patients (77 men) did not receive antihypertensive medication before nor during the study. Among the treated patients, 64% leceived all theft" medication upon awakening. BP was measured at 20-rain intervals fi'om 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. In untreated patients, 66.3% were non-dippers (nocturnal BP decline < 10% of the diurnal mean). In treated as compared to untreated patients, BP was highly reduced during diurnally active hours, but not during nocturnal sleep, in the absence of significant changes in activity. The percentage of non-dippers among treated patients was increased up to 69.4%. As a function of the cfl'cadian time of treatment, 81.5% of the patients with all drugs on awakening were non-dippers. This percentage was significantly 1educed to 49.4% in patients who received one antihypertensive drug before bedtime (P<0.001). Antihypertensive therapy, mostly given exclusively upon awakening, significantly modifies the cfl'cadian pattern of BP. In the elderly, pharrnacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient, as a function of the therapeutic coverage of the drugs and the baseline cfl'cadian BP profile of the patient. This chronopharrnacology therapeutic approach allows reducing the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk.
•]
PREVALENCE OF AN ALTERED NOCTURNAL DECLINE OF BLOOD PRESSURE IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES
C. Calvo, R. Herrnida, D. Ayala, M. Dominguez, M. Covelo, J. Lopez.
Hypertension and Vascular Risk Unit, Hospital CI nico Universitario, Santiago, Bioengineering & Chronobiology Labs., Univ. Vigo, Vigo, Spain The plevalence of a non-dipping pattern in type 2 diabetes mellitus (DM) is highly variable among different studies. Recent results have indicated that non-dipping in tleated hypertensive patients is markedly related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097-1104]. Accordingly, we have evaluated the prevalence of non-dipping in treated and untreated hypertensive patients with and without DM. We studied 234 hypertensive patients with DM (129 men), 59.8-4-11.3 years of age, and 1184 patients with grade 1-2 essential hypertension (512 men), 52.1-4-13.9 years of age. 88 patients with DM and 679 hypertensive controls were untreated at the time of the study. Blood pressure (BP) was measured by ambulatory monitoring (ABPM) at 20-rain intervals fi'om 07:00 to 23:00 hours and at 30-rain intervals at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-min intervals by wrist actigraphy. Diurnal and nocturnal means of BP obtained according to individual resting time determined by actigraphy were used to classify each patient as dipper o1" non-dipper (nocturnal BP decline < 10%). Among untleated patients without DM, 40.4% wele non-dippers. This percentage was significantly increased to 56.6% among treated patients. In DM, 65% of the untreated patients and 77% of the treated patients were non-dippers. More importantly, the percentage of risers (patients with nocturnal BP mean above the diurnal mean) increased fi'om 3.7% in untreated controls to 17.1% in untreated patients with DM, and fi'om 11.9% among treated hypertensive patients to a very high 28.1% among treated patients with DM. Results fi'om this study
~80~
EFFECTS OF ATORVASTATIN ON AMBULATORY BLOOD PRESSURE IN HYPERLIPIDEMIC PATIENTS W I T H UNTREATED MILD HYPERTENSION
C. Calvo, R. Herrnida, D. Ayala, J. Lopez, M. Dominguez, M. Covelo.
Hypertension and Vascular Risk Unit, Hospital CI nico Universitario, Santiago, Bioengineering & Chronobiology Labs., Univ. Vigo, Vigo, Spain Endothelium-dependent vasodilation is abnormal in hypercholesterolemic patients, while hypolipidemic therapy has been shown to improve endothelium dysfunction. Recent results have shown that atorvastatin, a HMG-CoA reductase inhibitor, conU'ibutes to a change in arterial stiffness independent of blood pressure (BP) level. Thus, some previous results have suggested that atorvastatin could have an added capacity to reduce BE Accordingly, we investigated the potential effects of atorvastatin on BP, independently of its effects on lipids, in patients with untreated mild hypertension who were evaluated by 48-hour ambulatory BP monitoring (ABPM). We studied 18 patients (6 men), 57.5-t- 10.9 years of age, with primary hypercholesterolemia (plasma cholesterol 250-300 mg/dl and triglycerides <400 mg/dl). Patients had mild hypertension diagnosed by the average of 6 conventional BP meastu'ements (> 140 or 90 mm Hg for systolic o1"diastolic BP) and corroborated fi'om the results of ABPM. They did not receive any antihypertensive medication neither before nor during the dtu'ation of this trial. Patients received atorvastatin (10 mg/day) for 3 months. BP was measured at 20-min intervals fi'om 07:00 to 23:00 hotu's and at 30-min intervals at night for 48 consecutive hotu's before and after 3 months of treatment with atorvastatin. Physical activity was simultaneously evaluated at 1-min intervals by wrist actigraphy. Cfl'cadian parameters of BP obtained for the patients before and after intervention by population multiple-components analysis were compared with a pahed nonparametric test. Results indicate highly statistically significant reductions in BP after 3 months of therapy with atorvastatin (7.2 and 4.6 mm Hg in the 24-hour mean of systolic and diastolic BP, respectively; p<0.001 in both cases). Despite this highly significant effect on BP, heart rate remained unchanged (declease on 0.7 beats/minute in 24-hour mean after therapy, P=0.576). Apart fi'om its previously demonstrated hypolipidemic effects, atorvastatin significantly reduces both systolic and diastolic BP, without affecting heart rate, in hypercholesterolemic patients with mild hypertension. This effect on BP could be mediated through the improvement of the endothelium dysfunction that characterizes these patients.
•]
OXIDIZED LDL IN MIDDLE-AGED TYPE 2 DIABETES PATIENTS WITHOUT CORONARY HEART DISEASE
Z. Caparevic, D. Begovic, D. Petrovic, S. Spasic, R. Cvetkovic. CHC Dr D. Misovic, University of Medicine, Department of Endocrinology, Belgrade, Serbia and Montenegro Background and Aims: Subjects with high plasma oxidized LDL (oxLDL) is at increased risk for development of coronary heart disease (CHD). The aim of this study was to estimate relations between ox LDL and other lipid risk factors for CHD in middle-aged subjects without CHD. Materials and Methods: Investigation was perforrned in 30 well controled diabetics type 2 patients (HbAlc<6.5%; FBG<5.5mmol/1) without CHD (group A) and in 27 hypercholesterolemic healthy middle-aged subjects (52,33-t-3,9 year (group B). Triglycerides, total-C and HDL-C were measmed by enzymatic methods. LDL-C was calculated using the Fliedewald fommla. Ox-LDL was detemained by ELISA (Mercodia AB, Uppsala, Sweden) Results: We found that ox LDL was slightly, but not significantly higher in group A than in group B (152.67-t-48.15 vs 126.91-t-43.46 IU/1; p>0.05). Conventional lipid profile (total Ch, LDL-Ch, HDL-Ch and Tg) as well as LDL/HDL ratio and Tg/HDL ratio, were similar between groups A and B. In group A we found significant colrelations between ox LDL with Tg (r=0.606: p=0.009), LDL/HDL ratio (r=0.553; p=0.02) and Tg/HDL (r=0.550; p=0.02). In group B we found that ox LDL significantly con'elated with total-Ch (r=0.747; p<0.005) and LDL-Ch (r=0.646; p=0.02).
74th EAS Congress, 17-20 April 2004, Seville, Spain