Rapid Left Ventricular Filling In Untreated Hypertensive SUbjects with or without Left Ventricular Hypertrophy* Giuseppe Licata, M.D.; Rosano Scaglione, M.D.; Gaspare Parrinello, M.D.; and Salvatore Corrao, M.D. In this study, independent contribution of age, UR, BMI, casual and ambulatory blood pressure, LVM and LVEF in evaluating diastolic filling have been investigated in 34 never-treated hypertensive patients and in 15 healthy normotensive subjects. All the subjects were free from coronary artery disease, valvular disease, heart failure, renal disease and psychiatric problems. Allthe hypertensive subjects (never treated) were subgrouped according to presence or absence of LVH. The PFR decreased sigaiOcantly and tPFR increased significantly in hypertensive patients in comparison with normotensive subjects and they did not change in the presence vs absence of LVH. The
PFR was inversely correlated with BMI, ale, J4·h mean SBP and with l4-h DBP. In multiple regrelsion analylil, PFR decreased with BMI, age, J4·h mean SBP and DBP but not with LVMI. These results suggest that BMI, age and l4-h mean blood pressure were the major determinants of PFa abnormalities in hypertensive patients. (Che" 1991,101,1&07-11)
years, relevant interest has been directed I ntothethelastdiastolic properties of the left ventricle in
In this case, impaired LV filling could represent an early marker of the pathologic effects of some diseases on the heart.v" In the present study we evaluated LV rapid filling in a group of unselected and untreated mild to moderate hypertensive patients and in a group of healthy normotensive subjects. Our final goal was to determine whether LVH can influence diastolic early filling in hypertensive patients and to evaluate the independent role exerted by age, blood pressure, HR, BMI and echocardiographic LVMI. For these reasons hypertensive patients were subgrouped according to the presence or absence of LVH.
hypertension. 1 Some abnormalities in LV diastolic function have been reported in hypertensive patients concerning those related to early filling and those related to compliance. These findings were derived from data obtained in man with noninvasive methods such as radionuclide and echocardiographic techniques.!" Although abnormalities in diastolic parameters are generally attributed to myocardial hypertrophy or to an increase in fibrous tissue or a change in its distribution, other factors such as age, HR, systolic parameters, overweight status, blood pressure and adrenergic activity could also influence LV filling. 3.6 Moreover, in several studies antihypertensive treatments have been discontinued for a few weeks before the diastolic function evaluation, but the possibility of altered function of the left ventricle cannot be excluded. For these reasons evaluating diastolic parameters in never-previously-treated hypertensive patients could reveal more correct data. It is already known that diastolic abnormalities commonly found in several cardiovascular diseases can be related to degree or duration of disease or reversibility of LVH
and to adequacy of control of blood pressure ...·?
According to some authors.P" LV rapid filling impairment may be present in patients with coronary artery disease or hypertension even in the absence of alterations in systolic function and in the lack of LVH. -Fn)m the Institute of Medical Pathology, University of Palermo, Palermo, Italy. Manuscript received January 3; revision accepted April 16. Reprint requests: Dr. Scaglione, Via LmnbarClIa 9, 90144 Iblermo,
Italy
EDV. end-diaatolic volume, LVH-left ventricular hypertro-
phy, LVM-left ventricular mul, LVMI-Ieft ventricular m..1 index, MBP. mean blood prellure, PFR- peak IIlIin. rate, tPFR - time to PFR
PATIENTS AND METHODS
lbtwnt Population Thirty-four mild to moderate hypertensive patients (20 males and 14 females) from 3.5 to 52 years of age and 15 healthy normotensive control subjects (seven males and eight females) from 37 to 54 yean of age were included in the study No significant differences In age, weight, height, OMI, sex distribution and HR were observed between normotensive and hypertensive subjects (1hble 1). All the subjects studied were consecutive never-treated essential hypertensive subjects or healthy subjects attending our hypertension research unit at University of Palermo, Italy, since November 1989and meeting all the following criteria: 1. No antihypertensive drug treatment. 2. Good quality of eehoeardiographlc and radionuchde imaging. 3. Agreement within t5 mm Hg between ambulatory blood pressure recording unit and standard mercury sphygmomanometer in at least three consecutive measurements taken simultaneously on the same arm before beginning the ambulatory recording. 4. Absence of cllnieal, electrocardiographic or eehoeardtographic evidence of coronary artery disease, valvular disease, heart failure, renal disease or psychiatric problems, Based on history and physical examination data, secondary causes CHEST I 102 I 5 I NOVEMBEA, 1812
1107
of hypertension were excluded. When necessary, specific instrumental investigations also were performed. We also had excluded from the study all subjects with symptoms and signs that may be associated with decreased blood volume such as dizziness, syncope and orthostatic hypotension. Essential hypertension was defined according to WHO criteria and with DBP values >90 mm Hg measured with the subject in the supine position on at least three visits at one-week intervals. Diastolic blood pressure refers to KorotkoffV phase. The MBP was calculated from the sum of DBP plus one third of the arterial pulse pressure. Arterial pressure also was measured with an appropriate large cuff in overweight subjects. Q The known duration of hypertension was more than two years in all the hypertensives. Heart rate was evaluated by electrocardtographie tracing. Healthy normotensive subjects were volunteer subjects chosen from among a group of subjects undergoing a clinical checkup and found to be healthy. All the subjects gave informed consent after they were given detailed Information about the study procedure, and the study was approved by the Sicily regional ethics committee. METHODS
Ambulatory Blood Pressure Measurements Ambulatory blood pressure was recorded by the portable fully automatic 'Iakeda TM2420 system connected through the serial interface (RS232) to an IBM personal system 2 computer which In our laboratory showed a correlation of r=O.96 with both SBP and 08P measured in the same arm using a mercury sphygmomanometer. The reading, editing and summary analysis of data provided by the unit was done by a dedicated software. The unit was set to take readings automatically every 15 min throughout the 24-h period. This approach has been well tolerated by many patients who were recruited. Only two hypertensive patients were excluded since the frequent recording of blood pressure during the night interfered with their sleep. A 24-h mean SBP and DPB reading was taken. Criteria for deleting individual blood pressure readings included a pulse pressure that was less than 12 mm Hg or an inconsistent increase and decrease in S8P or D8P greater than 30 mm Hg from previous or subsequent readings, Recordings were included in this
study only if at least 80 percent of the maximal number of 96 readings during the 24-h period passed the deletion criteria. Journals of activity, symptoms and emotions were carefully kept by the subjects for aid in the edlting process.
Echocardwgraphlc Study Two-dimensional and M-mode echocardiography examination was performed by an Esaote Biomedica computer-aided ultrasound system equipped with 2.5. and 3.5.MHz phased-array transducers. and a standard VHS video format was used to record it. Left ventricular mass and LVMI was calculated according to the Devereux method from necropsy validation studies. 10 Left ventricular hypertrophy was assumed in the presence of a LVMI>2 standard deviations of the sex-specific mean of a group of 110 normotensive subjects without a family history of hypertension providing the normal values for our laboratory (88 ± 16 wsq m for men and 75 ± 14 glsq m for women). Accordingly, patients were considered to have LVH when the LVMI values were> 120 wsq m for men and> 103 glsq m for women. The first assessment of LVM was performed by a preliminary Mmode eehooardiogram under two-dimensional control, also excluding either abnormal regional septal and parietal thickenings or wall motion abnormalities. When enrolled, patients underwent a new echocardtogram which was coded and used for the study. The most selective criterion was the complete absence of any previous antihypertensive therapy in the history. According to these criteria, nine hypertensive subjects (six males
1101
Table 1-Sum"",,,, DaIG for Nonno""" Gnd H",.,.,.,... SubJecll (MflGn Value:t SEM)
No.
Hypertensives Hypertensives Normotensives without LVH with LVU 15 25 9
Age (yean) 44.70±2.18O 1.65±0.004 Height (m) 8MI (kw'ml ) 25.10::t0.400 74.50± 1.300 HR (blmin) SBPc (mm Hg) 120.20± 1.500 D8Pc (mm Hg) 75.20± 1.900 M8Pc (mm Hg) 9O.4O± 1.600 SBP 24h (mm Hg) 118.20 ± 2.000 OBP 24h (mm Hg) 77.SO± 1.500 PFR(EOV/s) 3.58±0.250 tPFR (ms) 143.70±6.200 EF (%) 64.00± 1.500 LVMI (wma) 94.70±3.800
45.90± 1.800 44.3O± 1.700 1.84±0.003 1.65±0.002 26.5O±0.490 27.10±0.5OO 77.50± 1.200 76.20± 1.400 161.50 ± 3.SOO* 165.00±3.1OO* 99.10± 1.600*100.00± 1.500* 120.00± 1.900* 121.67::t2.000* 140.10 ± 2.100* 143.00 ± 2.000* 92.60::t 1.900* 95.00::t2.000* 2.77±0.390t 2.74±O.400t 182.00± 7.soot 184.00±8.000t 61.00± 1.400 6O.00± 1.300 110.00±6.000 129.00±7.lJOOt
*p
PFR was inversely correlated with BMI, ale, J4·h mean SBP and with l4-h DBP. In multiple regrelsion analylil, PFR decreased with BMI, age, J4·h mean SBP and DBP but not with LVMI. These results suggest that BMI, age and l4-h mean blood pressure were the major determinants of PFa abnormalities in hypertensive patients. (Che" 1991,101,1&07-11)
years, relevant interest has been directed I ntothethelastdiastolic properties of the left ventricle in
In this case, impaired LV filling could represent an early marker of the pathologic effects of some diseases on the heart.v" In the present study we evaluated LV rapid filling in a group of unselected and untreated mild to moderate hypertensive patients and in a group of healthy normotensive subjects. Our final goal was to determine whether LVH can influence diastolic early filling in hypertensive patients and to evaluate the independent role exerted by age, blood pressure, HR, BMI and echocardiographic LVMI. For these reasons hypertensive patients were subgrouped according to the presence or absence of LVH.
hypertension. 1 Some abnormalities in LV diastolic function have been reported in hypertensive patients concerning those related to early filling and those related to compliance. These findings were derived from data obtained in man with noninvasive methods such as radionuclide and echocardiographic techniques.!" Although abnormalities in diastolic parameters are generally attributed to myocardial hypertrophy or to an increase in fibrous tissue or a change in its distribution, other factors such as age, HR, systolic parameters, overweight status, blood pressure and adrenergic activity could also influence LV filling. 3.6 Moreover, in several studies antihypertensive treatments have been discontinued for a few weeks before the diastolic function evaluation, but the possibility of altered function of the left ventricle cannot be excluded. For these reasons evaluating diastolic parameters in never-previously-treated hypertensive patients could reveal more correct data. It is already known that diastolic abnormalities commonly found in several cardiovascular diseases can be related to degree or duration of disease or reversibility of LVH
and to adequacy of control of blood pressure ...·?
According to some authors.P" LV rapid filling impairment may be present in patients with coronary artery disease or hypertension even in the absence of alterations in systolic function and in the lack of LVH. -Fn)m the Institute of Medical Pathology, University of Palermo, Palermo, Italy. Manuscript received January 3; revision accepted April 16. Reprint requests: Dr. Scaglione, Via LmnbarClIa 9, 90144 Iblermo,
Italy
EDV. end-diaatolic volume, LVH-left ventricular hypertro-
phy, LVM-left ventricular mul, LVMI-Ieft ventricular m..1 index, MBP. mean blood prellure, PFR- peak IIlIin. rate, tPFR - time to PFR
PATIENTS AND METHODS
lbtwnt Population Thirty-four mild to moderate hypertensive patients (20 males and 14 females) from 3.5 to 52 years of age and 15 healthy normotensive control subjects (seven males and eight females) from 37 to 54 yean of age were included in the study No significant differences In age, weight, height, OMI, sex distribution and HR were observed between normotensive and hypertensive subjects (1hble 1). All the subjects studied were consecutive never-treated essential hypertensive subjects or healthy subjects attending our hypertension research unit at University of Palermo, Italy, since November 1989and meeting all the following criteria: 1. No antihypertensive drug treatment. 2. Good quality of eehoeardiographlc and radionuchde imaging. 3. Agreement within t5 mm Hg between ambulatory blood pressure recording unit and standard mercury sphygmomanometer in at least three consecutive measurements taken simultaneously on the same arm before beginning the ambulatory recording. 4. Absence of cllnieal, electrocardiographic or eehoeardtographic evidence of coronary artery disease, valvular disease, heart failure, renal disease or psychiatric problems, Based on history and physical examination data, secondary causes CHEST I 102 I 5 I NOVEMBEA, 1812
1107
of hypertension were excluded. When necessary, specific instrumental investigations also were performed. We also had excluded from the study all subjects with symptoms and signs that may be associated with decreased blood volume such as dizziness, syncope and orthostatic hypotension. Essential hypertension was defined according to WHO criteria and with DBP values >90 mm Hg measured with the subject in the supine position on at least three visits at one-week intervals. Diastolic blood pressure refers to KorotkoffV phase. The MBP was calculated from the sum of DBP plus one third of the arterial pulse pressure. Arterial pressure also was measured with an appropriate large cuff in overweight subjects. Q The known duration of hypertension was more than two years in all the hypertensives. Heart rate was evaluated by electrocardtographie tracing. Healthy normotensive subjects were volunteer subjects chosen from among a group of subjects undergoing a clinical checkup and found to be healthy. All the subjects gave informed consent after they were given detailed Information about the study procedure, and the study was approved by the Sicily regional ethics committee. METHODS
Ambulatory Blood Pressure Measurements Ambulatory blood pressure was recorded by the portable fully automatic 'Iakeda TM2420 system connected through the serial interface (RS232) to an IBM personal system 2 computer which In our laboratory showed a correlation of r=O.96 with both SBP and 08P measured in the same arm using a mercury sphygmomanometer. The reading, editing and summary analysis of data provided by the unit was done by a dedicated software. The unit was set to take readings automatically every 15 min throughout the 24-h period. This approach has been well tolerated by many patients who were recruited. Only two hypertensive patients were excluded since the frequent recording of blood pressure during the night interfered with their sleep. A 24-h mean SBP and DPB reading was taken. Criteria for deleting individual blood pressure readings included a pulse pressure that was less than 12 mm Hg or an inconsistent increase and decrease in S8P or D8P greater than 30 mm Hg from previous or subsequent readings, Recordings were included in this
study only if at least 80 percent of the maximal number of 96 readings during the 24-h period passed the deletion criteria. Journals of activity, symptoms and emotions were carefully kept by the subjects for aid in the edlting process.
Echocardwgraphlc Study Two-dimensional and M-mode echocardiography examination was performed by an Esaote Biomedica computer-aided ultrasound system equipped with 2.5. and 3.5.MHz phased-array transducers. and a standard VHS video format was used to record it. Left ventricular mass and LVMI was calculated according to the Devereux method from necropsy validation studies. 10 Left ventricular hypertrophy was assumed in the presence of a LVMI>2 standard deviations of the sex-specific mean of a group of 110 normotensive subjects without a family history of hypertension providing the normal values for our laboratory (88 ± 16 wsq m for men and 75 ± 14 glsq m for women). Accordingly, patients were considered to have LVH when the LVMI values were> 120 wsq m for men and> 103 glsq m for women. The first assessment of LVM was performed by a preliminary Mmode eehooardiogram under two-dimensional control, also excluding either abnormal regional septal and parietal thickenings or wall motion abnormalities. When enrolled, patients underwent a new echocardtogram which was coded and used for the study. The most selective criterion was the complete absence of any previous antihypertensive therapy in the history. According to these criteria, nine hypertensive subjects (six males
1101
Table 1-Sum"",,,, DaIG for Nonno""" Gnd H",.,.,.,... SubJecll (MflGn Value:t SEM)
No.
Hypertensives Hypertensives Normotensives without LVH with LVU 15 25 9
Age (yean) 44.70±2.18O 1.65±0.004 Height (m) 8MI (kw'ml ) 25.10::t0.400 74.50± 1.300 HR (blmin) SBPc (mm Hg) 120.20± 1.500 D8Pc (mm Hg) 75.20± 1.900 M8Pc (mm Hg) 9O.4O± 1.600 SBP 24h (mm Hg) 118.20 ± 2.000 OBP 24h (mm Hg) 77.SO± 1.500 PFR(EOV/s) 3.58±0.250 tPFR (ms) 143.70±6.200 EF (%) 64.00± 1.500 LVMI (wma) 94.70±3.800
45.90± 1.800 44.3O± 1.700 1.84±0.003 1.65±0.002 26.5O±0.490 27.10±0.5OO 77.50± 1.200 76.20± 1.400 161.50 ± 3.SOO* 165.00±3.1OO* 99.10± 1.600*100.00± 1.500* 120.00± 1.900* 121.67::t2.000* 140.10 ± 2.100* 143.00 ± 2.000* 92.60::t 1.900* 95.00::t2.000* 2.77±0.390t 2.74±O.400t 182.00± 7.soot 184.00±8.000t 61.00± 1.400 6O.00± 1.300 110.00±6.000 129.00±7.lJOOt
*p
