Risk factors related to left ventricular hypertrophy in elderly hypertensive patients
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《中华医药杂志》英文版
Department of Elder Internal Medicine, Peking University Third Hospital, Beijing 100083, China
Correspondence to ZHOU Ling, Department of Elder Internal Medicine, Peking University Third Hospital, Beijing 100083, China
Tel:+86-01-62017691-8238,E-mail:yun-zhu@263.net
[Abstract] Objective Left ventricular hypertrophy (LVH) is the main cause of heart failure. The aim of this investigation was to analyze the risk factors related to LVH in elderly hypertensive patients.Methods 155 male elderly patients with hypertensive disease were divided into two groups: hypertension with LVH (45) and hypertension without LVH (110). Blood pressure parameters using 24-hour ambulatory blood monitoring and plasma fibrinogen and lipid were compared between two groups. The effects of these factors on LVH were analyzed using stepwise multivariate regression analysis.Results There were no significant differences in age, body mass index, and body surface area between two groups; But 24-hour average pulse pressure, systolic blood pressure, casual pulse pressure, and plasma fibrinogen were significantly different; Widening 24-hour average pulse pressure were regarded as a significant independent risk factor of LVH.Conclusions Hypertension accompanied by LVH was caused by many factors such as long and non-controlled blood pressure, metabolic disorders etc. In which patients with widening pulse pressure may be much easier to appear LVH.
[Key words] hypertension; left ventricular hypertrophy; pulse pressure
INTRODUCTION
Hypertension is a very common disease in the world, especially in the elderly. Numerous studies, especially many prospective population-based studies such as Cardiovascular Health Study, The Heart Outcomes Prevention Evaluation (HOPE) trial, and Framingham Heart Study have shown that increases in diastolic and systolic blood pressure are positively associated with cardiac events, especially left ventricular hypertrophy (LVH) caused by hypertension is the main cause of heart failure[1~5]. LVH is an adaptive response to sustained increases in blood pressure and hormone imbalances. It is well investigated about the mechanisms of LVH at the molecular and biochemical level[6~8]. However, blood pressure is known to have a circadian variation. Many clinical conditions will affect the development of LVH. The relationships between 24-hour ambulatory blood pressure and LVH in the elderly are less well understood. So we investigated the ambulatory blood pressure parameters using 24-hour ambulatory blood monitoring and we also measured the plasma fibrinogen and lipid in order to analyze the risk factors of LVH.
MATERIAL AND METHODS
Subjects
Consecutive 155 elderly patients diagnosed as essential hypertension according to WHO guidelines hospitalized in our department during January 2002 to May 2004 were enrolled in the study. Patients with secondary hypertension, acute infective diseases, acute or old myocardial infarction, cardiomyopathy, stroke, hemopathy, diabetes mellitus, liver and renal function impairment and female were excluded.
Study Design
All the patients were divided into two groups according to echocardiography: hypertension with LVH ( LVH group ), n=45, mean age (73.93±5.84) years,ranging from 65 to 85 years. Hypertension without LVH ( EH group ) n=110, mean age (72.86±5.67) years, ranging from 65 to 89.
All patients agreed to participate in this study and the plan of this study was approved by the Local Ethical Committee.
Echocardiography
A definite cardiologist, unaware of clinical data,examined all subjects using the echocardiographic machine (GE Vivid 7). Left ventricular end diastolic dimension (LVEDD), interventricular septal thickness (IVST), and posterior wall thickness (PWT) were measured. The mean values obtained from the observer at least 3 measurements were computed to reduce the variability. Left ventricular mass (LVM) and body surface area (BSA) were calculated as follows: LVM=1.055×[(LVEDD+IVST+PWT)3-LVEDD3]-13.6, according to the method of Penn formula. BSA=0.0061×Height+0.0128×Body weight-0.1529, according to Stevenson formula. Left ventricular mass index (LVMI)＝LVM/BSA，LVMI>125 g/m2 were considered as LVH.
24-hour Ambulatory Blood Pressure
24-hour mean systolic blood pressure (24h SBP), 24-hour mean diastolic blood pressure (24h DBP), daytime mean systolic blood pressure (DSBP), daytime mean diastolic blood pressure (DDBP), nighttime mean systolic blood pressure (NSBP), nighttime mean diastolic blood pressure (NDBP), 24-hour mean pulse pressure (24 h PP) were measured and calculated automatically using 24-hour ambulatory blood pressure monitoring (NISSEI DS-250, Japan; COMPAQ, 1 mm Hg＝0.133 kPa). Automatic data editing excluded erroneous blood pressure measurements from the recording.
Casual Blood Pressure Measurements
All the patients were measured the blood pressure three times using a standard mercury sphygmomanometer at 3 minutes intervals after sitting for 5 minutes. The averaged value of these three measurements was called as casual blood pressure including casual systolic blood pressure (CSBP), casual diastolic blood pressure (CDBP), and casual pulse pressure (CPP).
Laboratory Measurements
All the patients had an ordinary diet, blood sample was taken in the morning after overnight fasting for≥12 h. Plasma fibrinogen levels were determined using clotting method by the apparatus (ACL9000, USA) automatically at the Central Laboratory of Peking University Third Hospital. Plasma lipid and uric acid levels were determined using terminal method by the apparatus (OLYMPUS AU 5400 and HITACH 17170A, Japan) automatically at the Central Laboratory of Peking University Third Hospital.
Statistical Analysis
Results were expressed as mean ± standard deviation. Students two-tailed unpaired t-test was analyzed between two groups. Logistic stepwise multivariate regression analysis was performed using SPSS 10. P<0.05 was considered as statistically significant.
RESULTS
Clinical Characteristics of Patients
The clinical characteristics of patients were summarized in Table 1. There were no significant differences in age, body mass index, and body surface areas betweentwo groups. But there was statistically significance in the course of hypertension between two groups. That is the longer the hypertensive course, the more LVH patients.
Table 1 Baseline Clinical Characteristics of Patients(mean ± SD or numbers)
*P<0.05 versus EH group.Summarization of the clinical characteristics of the participants in EH group and LVH group. Statistical analysis indicates that among EH group, LVH group has no significant difference from each other with respect to age, body mass index, body surface area, smoking and medication. But there was statistically significance in the course of hypertension between two groups. That is the longer the hypertensive course, the more LVH patients.
Blood Pressure Parameters Analysis
24-hour ambulatory blood pressure and casual blood pressure measurements were shown in Table 2. There were significant differences in 24 h SBP, DSBP,NSBP, NDBP, 24 h PP, CSBP, and CPP between two groups; but there were no significant differences in 24 h DBP, NDBP, and CDBP. From the table we can find there were more LVH complications with the increasing of pulse pressure and systolic blood pressure.
Blood Laboratory Parameters Analysis
In LVH group, blood fibrinogen concentration was significantly increased. But there were no significant differences in blood lipid and uric acid levels (Table 3).
Table 2 24-hour Ambulatory Blood Pressure and Casual Blood Pressure Measurements(mm Hg,mean ± SD)
Parameters of 24-hour ambulatory blood pressure and casual blood pressure. 24 hSBP: 24-hour mean systolic blood pressure, 24 hDBP: 24-hour mean diastolic blood pressure, DSBP: daytime mean systolic blood pressure, DDBP: daytime mean diastolic blood pressure, NSBP: nighttime mean systolic blood pressure, NDBP: nighttime mean diastolic blood pressure, 24 hPP: 24-hour mean pulse pressure, CSBP: casual systolic blood pressure, CDBP: casual diastolic blood pressure, and CPP: casual pulse pressure.There were significant differences in 24 h SBP, DSBP,NSBP, NDBP, 24 h PP, CSBP, and CPP between two groups; but there were no significant differences in 24 h DBP, NDBP, and CDBP. From the table we can find there were more LVH complications with the increasing of pulse pressure and systolic blood pressure.
Table 3 Blood Laboratory Parameters of Patients(mean ± SD)
*P<0.05 versus EH group.Summarization of laboratory findings of the participants in EH group and LVH group. Statistical analysis indicate that in LVH group, plasma fibrinogen level was significantly increased. There were no significant difference in plasma total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, ApoA1, ApoB, Lp (a) and uric acid levels.
Correlation Analysis
LVH was positive correlation with 24 h PP (r=0.71，P<0.01), with 24 h SBP (r=0.57,P<0.05), with CSBP (r=0.42，P<0.05), with CPP (r=0.33，P<0.05),with fibrinogen (r=0.26,P<0.05);with the widening of 24 h PP, the diameters of left atriums and left ventricles were increased (data was not shown).We further analyzed all the patients according to their 24 h PP. The patients were divided into three subgroups: 24 PP<60 mm Hg; 60~80 mm Hg and >80 mm Hg. With the widening of 24 h PP, the occurrence of LVH increased, there were significant differences among these subgroups, but there were not significant differences of fibrinogen levels among these subgroups (Table 4). In logistic stepwise multivariate regression analysis, 24 h PP was an independent predictor of LVH (B=0.2, 95% confidence interval: 1.132~1.319,P<0.001). LVH were regarded as a significant independent risk factor of LVH (Table 5).
Table 4 Analysis on Occurrence of LVH and Plasma Fibrinogen Levels among Different 24PP Subgroup(mean ± SD)
*P<0.05,**P<0.01 versus PP < 60 mm Hg subgroup.Analysis of all the patients according to their different 24 PP. The patients were divided into three subgroups: 24 PP<60 mm Hg; 60~80 mm Hg and >80 mm Hg. With the widening of 24 h PP, the occurrence of LVH increased, there were significant differences among every 24 PP subgroup, but there were not significant differences of fibrinogen levels among every 24 PP subgroup.
Table 5 Logistic Stepwise Multivariate Regression Analysis of Different Variables on LVH
Logistic stepwise multivariate regression analysis of different variables on LVH. Only 24 PP was an independent predictor of LVH. Other variables such as 24 SBP, CPP, fibrinogen, etc. were not entered the regression equation.
DISCUSSION
The mechanism of left ventricular hypertrophy in hypertension is so complicated that it is not very clear up to the present. We can know from hemodynamics that one of the mostly causes is increase of total peripheral resistance, including vascular tension and blood viscosity[6~11]. In recent years, people have been paying attention to pulse pressure, an index of arterial stiffening[12~13]. From our knowledge, systolic blood pressure continues to increase proportionally with age, while diastolic blood pressure levels off. So diastolic blood pressure is even less of an indicator in elderly patients, while pulse pressure, the gap between the systolic and diastolic blood pressure, may be the best predictor of cardiac events for all the blood pressure values. Pulse pressure has relationship with flexibility of artery wall. The widening of pulse pressure is regarded as resulting from a loss of compliance in large conduit arteries. Increasing evidence indicates the importance of pulse pressure as a risk factor for future cardiovascular events[14~17]. Framingham Heart Study showed that a 1-SD (16 mm Hg) increment in pulse pressure conferred a 55% increased risk for congestive heart failure[3]. We were particular interested in elderly group and in 24-hour ambulatory blood pressure monitoring for two reasons: first, less data for the risk factors of LVH are currently available for elderly men group; and second, assessment of pulse pressure in the elderly is best performed with use of ambulatory methods. Because that it has been the casual blood pressure measurements used most often to assess the risk of cardiovascular disease, but ambulatory blood monitoring which arising from 24-hour blood pressure measurements may have the greater reproducibility and much correctly. It is the synthesis of many times of measurements of blood pressure, so it could reflect the facts of blood pressure control. Casual blood pressure may not be representative of the pressure at other times. We found that with the increasing of 24 PP, 24 SBP, CSBP, and CPP, LVH was aggravating. And 24 PP was most correlated with LVH among 24 SBP, CSBP, and CPP. In one sentence, widening of 24 PP was an independent risk factor of LVH in elderly hypertensive patients. When pulse pressure increasing, conformability of main artery decrease, vascular wall become rigid, and resistance of peripheral artery increase. These will aggravate heart burden, which cause ventricular remodeling and cardiomyocytes hypertrophy. Therefore, evaluation of pulse pressure, especially 24 PP is more important in elderly people. Our study shows that ambulatory blood pressure especially its change, is so important in clinical work and further emphasizes the clinical value of ambulatory blood pressure monitoring in the elderly.
However, some clinical experiments show that left ventricular hypertrophy also appeared in hypertensive patients, although their blood pressure and pulse pressure controlled well, or in normal blood pressure patients[18]. Increasing of pulse pressure and systolic blood pressure are not simple factors of left ventricular hypertrophy. Blood viscosity and other factors are added, red blood cell aggregation is enhanced. It is possible to observe changes in microcirculation perfusion associated with a reduction in tissue oxygenation due in part to hemorheological changes such as increase in blood viscosity which favor an increase in peripheral resistance and cause or worsen hypertension and LVH[19]. Our study showed plasma fibrinogen increased in hypertensive patients with LVH. Plasma fibrinogen is related not only with coagulation system, but also with blood viscosity[20,21]. Some studies report that rise of fibrinogen is a marker of atherosclerosis and organ injury[22~26].The relation of fibrinogen to cardiovascular events is in part due to its role in the coagulation cascade. So we can partly explain the mechanism of cardiomyocytes compensatory hypertrophy: blood viscosity rising means blood stream resistance increasing, heart work augmenting, and microcirculation slowering even stopping and breakdown, therefore, cardiac ischemia and anoxia, Na-K-ATP enzyme activity decreased, thus cardiomyocytes injured, ventricular remodeling happened.
Blood lipid and uric acid have closely relationship with cardiovascular diseases, while our study only indicated that there was a incremental trend of lipid and uric acid in LVH group, but without statistical significance. Different metabolic conditions will influence the results of biochemical detection because the factors affecting body are complicated and variable. The further study depends on increasing samples and standardizing the detecting conditions as possible as we can.
Widening of pulse pressure related with LVH, while fibrinogen didnt increase with pulse pressure increasing. The effect of pulse pressure on cardiomyocytes may belong to dynamics changes, while that of fibrinogen on cardiomyocytes belong to non-dynamics factors. We can presume that pulse pressure and fibrinogen induce LVH from their individual access. Although 24 PP was an independent risk factor of predicting LVH, the relevant coefficient in the regression equation from our study was only 0.2. That means there were many factors affecting LVH in addition to 24 PP.
Our results above further provide beneficial clues on the reversion of LVH through decreasing 24 PP for clinical physicians. Anti-hypertensive treatment must reduce pulse pressure particularly in those elderly subjects with disproportionate systolic hypertension. When treating hypertension, we should pay attention to the change of fibrinogen and rectify it at the same time, which would benefit the progress of diseases and reduce the incidence and complications of cardiovascular diseases in the elderly.
REFERENCES
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2. Lonn E, Mathew J, Pogue J, et al. Relationship of eletrocardiographic left ventricular hypertrophy to mortality and cardiovascular morbidity in high-risk patients. Eur J Cardiovasc Prev Rehabil,2003,10:420-428.
3. Haider AW, Larson MG, Franklin SS, et al. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study. Ann Intern Med,2003,138:10-16.
4. Muiesan ML, Salvetti M, Monteduro C, et al. Left ventricular concentric geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients. Hypertension, 2004,43:731-738.
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8. Lips DJ, deWindt LJ, van-Kraaij DJ, et al. Molecular determinants of myocardial hypertrophy and failure: alternative pathways for beneficial and maladaptive hypertrophy. Eur Heart J, 2003,24:883-896.
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10. Ferrari AU. Modifications of the cardiovascular system with aging. Am J Geriatr Cardiol,2002,11:30-33.
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12. Benetos A, Waeber B, Izzo J, et al. Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffness: clinical applications. Am J Hypertens, 2002,15:1101-1108.
13. DeLeeuw PW, Birkenhager WH. The elderly hypertensive,cardiovascular and neurohormonal profile. Cardiovasc Drugs Ther, 2001,15:263-267.
14. Benetos A. Pulse pressure and cardiovascular risk. J Hypertens, 1999,17 (Suppl 5):S21-S24.
15. Chae CU, Pfeffer MA, Glynn RJ, et al. Increased pulse pressure and risk of heart failure in the elderly. JAMA, 1999, 281:634-639.
16. Kannel WB. Coronary heart disease risk factors in the elderly. Am J Geriatr Cardiol, 2002;11:101-107.
17. Laurent S, Boutouyrie P, Asmar R, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension, 2001,37:1236-1241.
18. Stiefel P, Miranda ML, Rodriguez-Puras MJ, et al. Glucose effectiveness is strongly related to left ventricular mass in subjects with stage Ⅰhypertension or high-normal blood pressure. Am J Hypertens,2004,17:146-153.
19. Frohlich ED. Fibrosis and ischemia: the real risks in hypertensive heart disease. Am J Hypertens,2001,14:194S-199S.
20. Lip GY, Blann AD, Jones AF, et al. Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy. Am J Cardiol, 1997,80:1566-1571.
21. de Simone G, Devereux RB, Chien S, et al. Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults. Circulation, 1990,81:107-117.
22. Lechi C, Gaino S, Zuliani V, et al. Elevated plasma fibrinogen levels in patients with essential hypertension are related to vascular complications. Int Angiol, 2003,22:72-78.
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24. Mauriello A, Sangiorgi G, Palmieri G, et al. Hyperfibrinogenemia is associated with specific histocytological composition and complications of atherosclerotic carotid plaques in patients affected by transient ischemic attacks. Circulation,2000,101:744-750.
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(Editor Jaque)(ZHU Yun,ZHANG Fan,ZHANG F)
Correspondence to ZHOU Ling, Department of Elder Internal Medicine, Peking University Third Hospital, Beijing 100083, China
Tel:+86-01-62017691-8238,E-mail:yun-zhu@263.net
[Abstract] Objective Left ventricular hypertrophy (LVH) is the main cause of heart failure. The aim of this investigation was to analyze the risk factors related to LVH in elderly hypertensive patients.Methods 155 male elderly patients with hypertensive disease were divided into two groups: hypertension with LVH (45) and hypertension without LVH (110). Blood pressure parameters using 24-hour ambulatory blood monitoring and plasma fibrinogen and lipid were compared between two groups. The effects of these factors on LVH were analyzed using stepwise multivariate regression analysis.Results There were no significant differences in age, body mass index, and body surface area between two groups; But 24-hour average pulse pressure, systolic blood pressure, casual pulse pressure, and plasma fibrinogen were significantly different; Widening 24-hour average pulse pressure were regarded as a significant independent risk factor of LVH.Conclusions Hypertension accompanied by LVH was caused by many factors such as long and non-controlled blood pressure, metabolic disorders etc. In which patients with widening pulse pressure may be much easier to appear LVH.
[Key words] hypertension; left ventricular hypertrophy; pulse pressure
INTRODUCTION
Hypertension is a very common disease in the world, especially in the elderly. Numerous studies, especially many prospective population-based studies such as Cardiovascular Health Study, The Heart Outcomes Prevention Evaluation (HOPE) trial, and Framingham Heart Study have shown that increases in diastolic and systolic blood pressure are positively associated with cardiac events, especially left ventricular hypertrophy (LVH) caused by hypertension is the main cause of heart failure[1~5]. LVH is an adaptive response to sustained increases in blood pressure and hormone imbalances. It is well investigated about the mechanisms of LVH at the molecular and biochemical level[6~8]. However, blood pressure is known to have a circadian variation. Many clinical conditions will affect the development of LVH. The relationships between 24-hour ambulatory blood pressure and LVH in the elderly are less well understood. So we investigated the ambulatory blood pressure parameters using 24-hour ambulatory blood monitoring and we also measured the plasma fibrinogen and lipid in order to analyze the risk factors of LVH.
MATERIAL AND METHODS
Subjects
Consecutive 155 elderly patients diagnosed as essential hypertension according to WHO guidelines hospitalized in our department during January 2002 to May 2004 were enrolled in the study. Patients with secondary hypertension, acute infective diseases, acute or old myocardial infarction, cardiomyopathy, stroke, hemopathy, diabetes mellitus, liver and renal function impairment and female were excluded.
Study Design
All the patients were divided into two groups according to echocardiography: hypertension with LVH ( LVH group ), n=45, mean age (73.93±5.84) years,ranging from 65 to 85 years. Hypertension without LVH ( EH group ) n=110, mean age (72.86±5.67) years, ranging from 65 to 89.
All patients agreed to participate in this study and the plan of this study was approved by the Local Ethical Committee.
Echocardiography
A definite cardiologist, unaware of clinical data,examined all subjects using the echocardiographic machine (GE Vivid 7). Left ventricular end diastolic dimension (LVEDD), interventricular septal thickness (IVST), and posterior wall thickness (PWT) were measured. The mean values obtained from the observer at least 3 measurements were computed to reduce the variability. Left ventricular mass (LVM) and body surface area (BSA) were calculated as follows: LVM=1.055×[(LVEDD+IVST+PWT)3-LVEDD3]-13.6, according to the method of Penn formula. BSA=0.0061×Height+0.0128×Body weight-0.1529, according to Stevenson formula. Left ventricular mass index (LVMI)＝LVM/BSA，LVMI>125 g/m2 were considered as LVH.
24-hour Ambulatory Blood Pressure
24-hour mean systolic blood pressure (24h SBP), 24-hour mean diastolic blood pressure (24h DBP), daytime mean systolic blood pressure (DSBP), daytime mean diastolic blood pressure (DDBP), nighttime mean systolic blood pressure (NSBP), nighttime mean diastolic blood pressure (NDBP), 24-hour mean pulse pressure (24 h PP) were measured and calculated automatically using 24-hour ambulatory blood pressure monitoring (NISSEI DS-250, Japan; COMPAQ, 1 mm Hg＝0.133 kPa). Automatic data editing excluded erroneous blood pressure measurements from the recording.
Casual Blood Pressure Measurements
All the patients were measured the blood pressure three times using a standard mercury sphygmomanometer at 3 minutes intervals after sitting for 5 minutes. The averaged value of these three measurements was called as casual blood pressure including casual systolic blood pressure (CSBP), casual diastolic blood pressure (CDBP), and casual pulse pressure (CPP).
Laboratory Measurements
All the patients had an ordinary diet, blood sample was taken in the morning after overnight fasting for≥12 h. Plasma fibrinogen levels were determined using clotting method by the apparatus (ACL9000, USA) automatically at the Central Laboratory of Peking University Third Hospital. Plasma lipid and uric acid levels were determined using terminal method by the apparatus (OLYMPUS AU 5400 and HITACH 17170A, Japan) automatically at the Central Laboratory of Peking University Third Hospital.
Statistical Analysis
Results were expressed as mean ± standard deviation. Students two-tailed unpaired t-test was analyzed between two groups. Logistic stepwise multivariate regression analysis was performed using SPSS 10. P<0.05 was considered as statistically significant.
RESULTS
Clinical Characteristics of Patients
The clinical characteristics of patients were summarized in Table 1. There were no significant differences in age, body mass index, and body surface areas betweentwo groups. But there was statistically significance in the course of hypertension between two groups. That is the longer the hypertensive course, the more LVH patients.
Table 1 Baseline Clinical Characteristics of Patients(mean ± SD or numbers)
*P<0.05 versus EH group.Summarization of the clinical characteristics of the participants in EH group and LVH group. Statistical analysis indicates that among EH group, LVH group has no significant difference from each other with respect to age, body mass index, body surface area, smoking and medication. But there was statistically significance in the course of hypertension between two groups. That is the longer the hypertensive course, the more LVH patients.
Blood Pressure Parameters Analysis
24-hour ambulatory blood pressure and casual blood pressure measurements were shown in Table 2. There were significant differences in 24 h SBP, DSBP,NSBP, NDBP, 24 h PP, CSBP, and CPP between two groups; but there were no significant differences in 24 h DBP, NDBP, and CDBP. From the table we can find there were more LVH complications with the increasing of pulse pressure and systolic blood pressure.
Blood Laboratory Parameters Analysis
In LVH group, blood fibrinogen concentration was significantly increased. But there were no significant differences in blood lipid and uric acid levels (Table 3).
Table 2 24-hour Ambulatory Blood Pressure and Casual Blood Pressure Measurements(mm Hg,mean ± SD)
Parameters of 24-hour ambulatory blood pressure and casual blood pressure. 24 hSBP: 24-hour mean systolic blood pressure, 24 hDBP: 24-hour mean diastolic blood pressure, DSBP: daytime mean systolic blood pressure, DDBP: daytime mean diastolic blood pressure, NSBP: nighttime mean systolic blood pressure, NDBP: nighttime mean diastolic blood pressure, 24 hPP: 24-hour mean pulse pressure, CSBP: casual systolic blood pressure, CDBP: casual diastolic blood pressure, and CPP: casual pulse pressure.There were significant differences in 24 h SBP, DSBP,NSBP, NDBP, 24 h PP, CSBP, and CPP between two groups; but there were no significant differences in 24 h DBP, NDBP, and CDBP. From the table we can find there were more LVH complications with the increasing of pulse pressure and systolic blood pressure.
Table 3 Blood Laboratory Parameters of Patients(mean ± SD)
*P<0.05 versus EH group.Summarization of laboratory findings of the participants in EH group and LVH group. Statistical analysis indicate that in LVH group, plasma fibrinogen level was significantly increased. There were no significant difference in plasma total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, ApoA1, ApoB, Lp (a) and uric acid levels.
Correlation Analysis
LVH was positive correlation with 24 h PP (r=0.71，P<0.01), with 24 h SBP (r=0.57,P<0.05), with CSBP (r=0.42，P<0.05), with CPP (r=0.33，P<0.05),with fibrinogen (r=0.26,P<0.05);with the widening of 24 h PP, the diameters of left atriums and left ventricles were increased (data was not shown).We further analyzed all the patients according to their 24 h PP. The patients were divided into three subgroups: 24 PP<60 mm Hg; 60~80 mm Hg and >80 mm Hg. With the widening of 24 h PP, the occurrence of LVH increased, there were significant differences among these subgroups, but there were not significant differences of fibrinogen levels among these subgroups (Table 4). In logistic stepwise multivariate regression analysis, 24 h PP was an independent predictor of LVH (B=0.2, 95% confidence interval: 1.132~1.319,P<0.001). LVH were regarded as a significant independent risk factor of LVH (Table 5).
Table 4 Analysis on Occurrence of LVH and Plasma Fibrinogen Levels among Different 24PP Subgroup(mean ± SD)
*P<0.05,**P<0.01 versus PP < 60 mm Hg subgroup.Analysis of all the patients according to their different 24 PP. The patients were divided into three subgroups: 24 PP<60 mm Hg; 60~80 mm Hg and >80 mm Hg. With the widening of 24 h PP, the occurrence of LVH increased, there were significant differences among every 24 PP subgroup, but there were not significant differences of fibrinogen levels among every 24 PP subgroup.
Table 5 Logistic Stepwise Multivariate Regression Analysis of Different Variables on LVH
Logistic stepwise multivariate regression analysis of different variables on LVH. Only 24 PP was an independent predictor of LVH. Other variables such as 24 SBP, CPP, fibrinogen, etc. were not entered the regression equation.
DISCUSSION
The mechanism of left ventricular hypertrophy in hypertension is so complicated that it is not very clear up to the present. We can know from hemodynamics that one of the mostly causes is increase of total peripheral resistance, including vascular tension and blood viscosity[6~11]. In recent years, people have been paying attention to pulse pressure, an index of arterial stiffening[12~13]. From our knowledge, systolic blood pressure continues to increase proportionally with age, while diastolic blood pressure levels off. So diastolic blood pressure is even less of an indicator in elderly patients, while pulse pressure, the gap between the systolic and diastolic blood pressure, may be the best predictor of cardiac events for all the blood pressure values. Pulse pressure has relationship with flexibility of artery wall. The widening of pulse pressure is regarded as resulting from a loss of compliance in large conduit arteries. Increasing evidence indicates the importance of pulse pressure as a risk factor for future cardiovascular events[14~17]. Framingham Heart Study showed that a 1-SD (16 mm Hg) increment in pulse pressure conferred a 55% increased risk for congestive heart failure[3]. We were particular interested in elderly group and in 24-hour ambulatory blood pressure monitoring for two reasons: first, less data for the risk factors of LVH are currently available for elderly men group; and second, assessment of pulse pressure in the elderly is best performed with use of ambulatory methods. Because that it has been the casual blood pressure measurements used most often to assess the risk of cardiovascular disease, but ambulatory blood monitoring which arising from 24-hour blood pressure measurements may have the greater reproducibility and much correctly. It is the synthesis of many times of measurements of blood pressure, so it could reflect the facts of blood pressure control. Casual blood pressure may not be representative of the pressure at other times. We found that with the increasing of 24 PP, 24 SBP, CSBP, and CPP, LVH was aggravating. And 24 PP was most correlated with LVH among 24 SBP, CSBP, and CPP. In one sentence, widening of 24 PP was an independent risk factor of LVH in elderly hypertensive patients. When pulse pressure increasing, conformability of main artery decrease, vascular wall become rigid, and resistance of peripheral artery increase. These will aggravate heart burden, which cause ventricular remodeling and cardiomyocytes hypertrophy. Therefore, evaluation of pulse pressure, especially 24 PP is more important in elderly people. Our study shows that ambulatory blood pressure especially its change, is so important in clinical work and further emphasizes the clinical value of ambulatory blood pressure monitoring in the elderly.
However, some clinical experiments show that left ventricular hypertrophy also appeared in hypertensive patients, although their blood pressure and pulse pressure controlled well, or in normal blood pressure patients[18]. Increasing of pulse pressure and systolic blood pressure are not simple factors of left ventricular hypertrophy. Blood viscosity and other factors are added, red blood cell aggregation is enhanced. It is possible to observe changes in microcirculation perfusion associated with a reduction in tissue oxygenation due in part to hemorheological changes such as increase in blood viscosity which favor an increase in peripheral resistance and cause or worsen hypertension and LVH[19]. Our study showed plasma fibrinogen increased in hypertensive patients with LVH. Plasma fibrinogen is related not only with coagulation system, but also with blood viscosity[20,21]. Some studies report that rise of fibrinogen is a marker of atherosclerosis and organ injury[22~26].The relation of fibrinogen to cardiovascular events is in part due to its role in the coagulation cascade. So we can partly explain the mechanism of cardiomyocytes compensatory hypertrophy: blood viscosity rising means blood stream resistance increasing, heart work augmenting, and microcirculation slowering even stopping and breakdown, therefore, cardiac ischemia and anoxia, Na-K-ATP enzyme activity decreased, thus cardiomyocytes injured, ventricular remodeling happened.
Blood lipid and uric acid have closely relationship with cardiovascular diseases, while our study only indicated that there was a incremental trend of lipid and uric acid in LVH group, but without statistical significance. Different metabolic conditions will influence the results of biochemical detection because the factors affecting body are complicated and variable. The further study depends on increasing samples and standardizing the detecting conditions as possible as we can.
Widening of pulse pressure related with LVH, while fibrinogen didnt increase with pulse pressure increasing. The effect of pulse pressure on cardiomyocytes may belong to dynamics changes, while that of fibrinogen on cardiomyocytes belong to non-dynamics factors. We can presume that pulse pressure and fibrinogen induce LVH from their individual access. Although 24 PP was an independent risk factor of predicting LVH, the relevant coefficient in the regression equation from our study was only 0.2. That means there were many factors affecting LVH in addition to 24 PP.
Our results above further provide beneficial clues on the reversion of LVH through decreasing 24 PP for clinical physicians. Anti-hypertensive treatment must reduce pulse pressure particularly in those elderly subjects with disproportionate systolic hypertension. When treating hypertension, we should pay attention to the change of fibrinogen and rectify it at the same time, which would benefit the progress of diseases and reduce the incidence and complications of cardiovascular diseases in the elderly.
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(Editor Jaque)(ZHU Yun,ZHANG Fan,ZHANG F)