原发性高血压患者血压分级与脉搏波速度的关系

目的 探讨原发性高血压(EH)患者血压分级与肱动脉踝动脉脉搏波速度(baPWV)之间的关系和影响baPWV的危险因素.方法 测定252例EH患者诊室血压、动态血压和血生化指标,应用脉搏波传导速度(PWV)自动测量系统测定患者baPWV,进行不同血压水平和baPWV之间比较.结果 1)高血压3级组的baP-WV显著高于高血压1级组(P<0.05);高血压3级组空腹血糖(FPG)水平高于1级高血压组(P<0.05);高血压3级组餐后2 h血糖(2 h PG)水平高于1级、2级高血压组(P<0.05).2)baPWV与24 h平均收缩压(SBP)、平均脉压(PP)、白昼SBP、白昼PP、白昼及夜间SBP负荷呈显著正相关(P均<0.05).3)baPWV增高者的年龄、SBP、舒张压(DBP)、三酰甘油(TG)均高于正常对照组(P均<0.05).4)baPWV与年龄、SBP、PP、FPG、2 h PG呈显著正相关(P<0.05),其中年龄与FPG是影响baPWV的独立危险因素.结论 伴有心血管危险因素的原发性高血压3级患者动脉僵硬程度显著增加;24 h平均SBP及PP、白昼及夜间SBP负荷越高,baPWV越高;年龄、FPG升高是影响baPWV的独立危险因素.     

原发性高血压患者血压分级与脉搏波速度的关系

目的探讨原发性高血压(EH)患者血压分级与肱动脉踝动脉脉搏波速度(baPWV)之间的关系和影响 baPWV 的危险因素。方法测定252例 EH 患者诊室血压、动态血压和血生化指标,应用脉搏波传导速度(PWV)自动测量系统测定患者 baPWV,进行不同血压水平和 baPWV 之间比较。结果 1)高血压3级组的 baP-WV 显著高于高血压1级组(P<0.05);高血压3级组空腹血糖(FPG)水平高于1级高血压组(P<0.05);高血压3级组餐后2 h血糖(2 h PG)水平高于1级、2级高血压组(P<0.05)。2)baPWV 与24 h 平均收缩压(SBP)、平均脉压(PP)、白昼 SBP、白昼 PP、白昼及夜间 SBP 负荷呈显著正相关(P 均<0.05)。3)baPWV 增高者的年龄、SBP、舒张压(DBP)、三酰甘油(TG)均高于正常对照组(P 均<0.05)。4)baPWV 与年龄、SBP、PP、FPG、2 h PG 呈显著正相关(P<0.05),其中年龄与 FPG 是影响 baPWV 的独立危险因素。结论伴有心血管危险因素的原发性高血压3级患者动脉僵硬程度显著增加;24 h 平均 SBP 及 PP、...     

高血压患者和健康人动态动脉硬化指数与脉搏波传导速度比较

目的:比较不同年龄、血压水平的健康人和高血压患者动态动脉硬化指数(AASI)与脉搏波传导速度(PWV)的差异,分析其相关性,探讨AASI作为评价动脉弹性指标的可行性。方法:选取健康体检者167例和高血压患者148例,分别按年龄和血压分级标准分组,进行PWV测量及24h动态血压监测,根据24h动态舒张压与动态收缩压之间的关系,计算出回归斜率,AASI定义为1减去该斜率,对AASI与PWV进行比较研究。结果:随着年龄不断增长,两组的PWV和AASI值逐渐升高(P0.05～0.01),两组女性AASI明显高于男性[健康对照组(0.55±0.18)∶(0.48±0.15),高血压组(0.61±0.16)∶(0.55±0.17),P均0.01]。PWV在性别上无显著差异(P0.05);校正年龄因素影响后,高血压组PWV、AASI明显比健康对照组高,并随着血压水平的升高,PWV、AASI逐渐升高(P0.05～0.01);Pearson相关性分析表明:AASI与年龄、体重指数、24h平均收缩压、24h脉压、PWV呈正相关(r=0.106～0.573,P0.05～0.001),与24h平均舒张压呈负相关,其中以PWV相关性最显著(r=0.573,P0.001)。结论:年龄、血压、脉压和PWV都与AASI呈正相关;AASI作为评价动脉弹性指标,可能比测量血压更能准确反映血管功能状态,有助于筛选出处于亚临床状态的心血管病人。     

老年单纯性收缩期高血压的24h血压及脉压特征

目的　了解老年单纯性收缩期高血压的 2 4h动态血压特征及脉压情况。方法　收集 2 0 0 1年以来门诊及病房的老年单纯性收缩期高血压 12 1例 ,男 5 3例 ,女 6 8例 ,年龄≥ 6 0岁。所有患者均作 2 4h动态血压监测。结果　随着年龄的增加 ,老年单纯收缩期高血压患者的诊室、2 4h、白天及夜间的收缩压 (SBP)均有不同程度的升高 ,舒张压 (DBP)却有不同程度的下降 ;所有患者的脉压 (PP)均明显增大 (PP >6 5mmHg) ;不同年龄组之间 2 4h、白天、夜间的PP随着年龄的增大而增加 (P <0 .0 5 )。年龄 >70岁组的 2 4h和白天的DBP水平显著低于年龄≤ 70岁组 (P <0 .0 5 )。体重指数 (BMI)≥ 2 5患者组的 2 4h平均SBP、夜间平均SBP及DBP均高于BMI<2 5组 (P <0 .0 5 )。动态血压的夜间SBP和DBP的下降率分别为 4 .6 %和 7.0 % ,昼夜节律减弱。白天和夜间的SBP负荷明显增加 ,而DBP负荷正常。结论　随着年龄的增大 ,老年单纯收缩期高血压患者的诊室、2 4h、白天及夜间的SBP均有升高 ,SBP负荷和脉压明显增加 ;昼夜节律减弱     

高血压患者动态动脉僵硬指数与血压变异性的关系

目的探讨高血压患者动态动脉僵硬指数(AASI)与血压变异性(BPV)的关系。方法入选2009-03-2011-10中国医科大学附属第一医院就诊的高血压患者119例,所有患者均行24h动态血压监测。AASI定义为1减去24h舒张压和收缩压的回归系数。依据AASI水平,分为4组:AASI<0.30、0.30～<0.41、0.41～<0.52、≥0.52。结果相关性分析显示,AASI分别与年龄(r=0.301,P<0.01)、24h收缩压(r=0.276,P=0.001)、白昼收缩压(r=0.225,P=0.008)、夜间收缩压(r=0.366,P<0.01)、24h脉压(r=0.510,P<0.01)、24h收缩压标准差(r=0.297,P=0.001)呈正相关,而与24h舒张压标准差(r=-0.256,P=0.002)、24h平均心率标准差(r=-0.205,P=0.017)及24h平均动脉压标准差(r=-0.202,P=0.017)呈负相关。多元线性逐步回归分析显示,AASI与24h脉压和24h收缩压标准差呈正相关(β=0.321,β=0.725,均P<0.01),与24h舒张压标准差和24h平均动脉压标准差呈负相关(β=-0.428,β=-0.346,均P<0.01)。结论 AASI与BPV密切相关。     

老年人血管硬化与血压变异的相关性

目的探讨老年人血管硬化与血压变异的相关性,旨在为临床诊断及防控心脑血管疾病提供参考依据。方法 160例老年高血压患者,观察其总胆固醇、高密度脂蛋白、三酰甘油、低密度脂蛋白、血肌酐、尿酸等血生化指标,采取肱踝脉搏波传导速度(baPWV)测定,24 h动态血压监测。结果高baPWV组年龄与高血压病程均明显高于低baPWV组,24 h平均收缩压(24 h SBP)、24 h平均脉压(24 h PP)、昼间平均SBP(dSBP)、昼间平均PP(dPP)、夜间平均SBP(nSBP)、夜间平均PP(nPP)明显高于低baPWV组,24 h SBP标准差(24 h SSD)、白天SBP标准差(dSSD)、夜间SBP标准差(nSSD)明显高于低baPWV组(均P0.05)。Pearson线性单因素分析证实,baPWV与患者年龄、高血压病程、低密度脂蛋白、24 h SBP、dSBP、nSBP、24 h SSD、dSSD、nSSD、24 h PP、dPP、nPP呈正相关。多元线性逐步回归分析证实,高血压患者24 h SSD、24 h PP与血管硬化有独立相关性。结论老年高血压患者血压变异与血管硬化呈正相关。     

动态脉压指数与冠脉狭窄程度的相关性研究

目的 探讨动态各脉压指数(PPI)与冠脉病变狭窄程度的关系.方法 对156例入选病例均行冠脉造影术,其中男103例,女53例.年龄33岁～81岁(59.15岁±10.60岁).所有病例均于术后监测24 h动态血压,并计算各病例24 h PPI、白昼PPI及夜间PPI.冠脉病变的狭窄程度用病变的血管支数及Gensini积分表示.结果 冠脉狭窄组24 h动态血压监测,无论24 h、白昼还是夜间,其收缩压(SBP)、脉压(PP)及PPI均显著高于冠脉正常组(P＜0.05),且SBP、PP及PPI均随冠脉血管狭窄支数的增加而逐渐增加.多因素Logistic回归分析结果显示动态各PPI均与冠心病(CHD)冠脉狭窄程度的关系最为密切;且夜间PPI较其他因素与CHD冠脉狭窄程度的关系更密切.结论 动态各PPI均是CHD冠脉狭窄发生发展的独立危险因素,且夜间PPI的预测价值更佳.     

动态动脉硬化指数与老年高血压患者心律失常的相关性

目的研究动态动脉硬化指数(AASI)与老年高血压患者心律失常的相关性。方法选取2011年1月至2012年12月该院150例老年高血压患者,按AASI高低将患者分为两组,AASI>0.49(中位数)为高值组,AASI≤0.49为低值组。记录分析两组动态血压及心律失常发生情况。结果高值组患者24 h收缩压(SBP)、24 h脉压(PP)高于低值组,24 h舒张压(DBP)低于低值组(均P<0.05)。高值组患者室性期前收缩、复杂性室性心律失常、房性期前收缩、复杂性房性心律失常、左室高电压发生率均高于低值组(均P<0.05)。结论老年高血压患者动态AASI升高可能会导致患者更易发生心律失常。     

动脉僵硬度指数与冠脉狭窄程度的相关性研究

目的 探讨动态血压参数动脉僵硬度指数(AASI)与冠脉病变严重程度的关系.方法 对252例入选病例行冠脉造影术.冠状动脉病变损害程度采用Gensini法计分,所有病例均于术前监测24 h动态血压.记录参数:24 h收缩压(sBP)、24 h舒张压(DBP),以DBP为纵坐标,SBP为横坐标,求出斜率(β),动脉僵硬度指数=1-β.结果 高血压组较非高血压组冠心病患病率明显增高(P＜0.05).高血压组患者冠脉三支血管病变的患病率显著高于非高血压组(P＜0.05).冠脉狭窄组24 h动态血压监测,无论24 h、白昼还是夜间动脉僵硬度指数均显著高于冠脉正常组(P＜0.05).多因素Logistic回归分析结果显示:各动脉僵硬度指数与冠心病(CHD)冠脉狭窄程度的关系最为密切,且夜问动脉僵硬度指数较其他因素与CHD冠脉狭窄程度的关系更密切(P＜0.05).结论 动脉僵硬度指数是CHD冠脉狭窄发生发展的独立危险因素,动脉僵硬度指数与CHD冠昧狭窄程度的关系较为密切.     

行冠脉造影老年患者212例脉压、脉压指数与冠状动脉病变的关系

高血压在冠心病的发生发展中起较大作用,且血压水平与冠心病发病率有密切关系.另外,有研究<'[1-3]>表明动脉脉压(主动脉脉压、肱动脉脉压)能够反映动脉弹性情况,与收缩压(SBP)和舒张压(DBP)相比能够更好地预测心血管事件的发生.但脉压(PP)本身具有一定的可变性,脉压指数(PPI)能够同时反映血管的固有和动态的顺应性,并且变化幅度小于PP<'[4]>.本研究通过24 h监测行冠脉造影的老年住院患者血压取其平均值,探讨肱动脉PP、PPI与冠状动脉关系.     

Ambulatory arterial stiffness index or pulse pressure: which correlates better with arterial stiffness in resistant hypertension?

The ambulatory arterial stiffness index (AASI) is a recently proposed index derived from 24-h ambulatory blood pressure monitoring (ABPM) for the evaluation of arterial stiffness. In this cross-sectional study we investigated whether AASI reflects arterial stiffness in patients with resistant hypertension by comparing AASI and ambulatory pulse pressure (PP) with aortic pulse wave velocity (PWV), a measure of arterial stiffness, in 391 resistant hypertensives. Clinical, laboratory and echocardiographic variables, 24-h ABPM and aortic PWV (measured using the Complior device) were obtained. AASI was calculated as 1--the regression slope of 24-h diastolic on systolic blood pressure (BP). Statistical analysis involved single and multiple linear regressions to assess the correlations between the two ABPM variables and PWV, both unadjusted and adjusted for potential confounders (age, gender, body height, presence of diabetes, 24-h mean arterial pressure [MAP], heart rate, and nocturnal BP reduction). Ambulatory PP and aortic PWV were independently associated with age, gender, presence of diabetes, and 24-h MAP, whereas AASI was associated with age, diabetes, and nocturnal diastolic BP reduction. PP showed stronger unadjusted (r=0.39, p<0.001) and adjusted (r=0.22, p<0.001) correlations with aortic PWV than AASI (r=0.12, p=0.032 and r= -0.04, p=0.47, respectively). In the analysis of subgroups stratified by gender, age, presence of atherosclerotic diseases and diabetes, dipping pattern, and ambulatory BP control, the superiority of PP over AASI was apparent in all subgroups. In conclusion, 24-h ambulatory PP was better correlated to arterial stiffness, as evaluated by aortic PWV, than the novel AASI, in patients with resistant hypertension.     

Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study

We hypothesized that the dynamic relation between diastolic and systolic blood pressure over 24 hours provides a measure of arterial stiffness and might, therefore, predict cardiovascular mortality over and above pulse pressure. At baseline, while not on antihypertensive medication, 11 291 patients (mean age, 54.6 years; 5965 women) underwent ambulatory blood pressure monitoring. Using all of the blood pressure readings, we plotted diastolic against systolic blood pressure from each individual and calculated the regression slope. The ambulatory arterial stiffness index (AASI) was defined as 1 minus this regression slope. Over a median follow-up of 5.3 years, 566 cardiovascular deaths occurred, including 151 from stroke and 358 from cardiac disorders. Before and after adjustment for other cardiovascular risk factors, AASI and pulse pressure significantly predicted total cardiovascular mortality. AASI was a stronger predictor than pulse pressure for stroke (mutually adjusted relative hazard ratios for 1 SD increase, 1.21 versus 1.04; P=0.02 versus 0.66) with the opposite trend for cardiac mortality (relative hazard ratios, 1.03 versus 1.21; P=0.63 versus 0.002). In subjects with normal daytime ambulatory blood pressure (<135/<85 mm Hg), AASI was more predictive than pulse pressure of cardiovascular mortality (1.26 versus 0.96; P=0.04 versus 0.70) and of stroke mortality (1.81 versus 1.12; P=0.007 versus 0.58), whereas neither independently predicted cardiac mortality (1.11 versus 0.89; P=0.47 versus 0.40). AASI is a novel measure of arterial stiffness, which can be readily determined from ambulatory blood pressure recordings and which independently predicts cardiovascular mortality, even in normotensive subjects.     

Ambulatory arterial stiffness index predicts stroke in a general population

OBJECTIVE: The ambulatory arterial stiffness index (AASI) can be computed from individual 24-h blood pressure recordings. METHODS: We investigated the prognostic value of AASI and 24-h pulse pressure in a random sample of 1829 Danes, aged 40-70 years. We adjusted for sex, age, body mass index, mean arterial pressure, smoking, diabetes, ratio of total to high-density lipoprotein cholesterol, and history of cardiovascular disease with Cox regression. RESULTS: Over a median follow-up of 9.4 years, incidences of fatal and nonfatal endpoints were 40 for stroke, 150 for coronary heart disease, and 212 for cardiovascular events. In fully adjusted models, the hazard ratios associated with 1 SD increase (0.14 U) in the AASI were 1.62 (95% confidence interval, 1.14-2.28; P = 0.007) for stroke, 0.96 (0.80-1.14; P = 0.62) for coronary heart disease, and 1.06 (0.91-1.23; P = 0.49) for cardiovascular events. None of these ratios reached significance for pulse pressure (P > 0.47). The AASI still predicted stroke after excluding individuals with previous cardiovascular disease or after adjustment for systolic and/or diastolic blood pressure instead of mean arterial pressure. CONCLUSIONS: In a randomly recruited European population, the AASI was a strong predictor of stroke, beyond traditional cardiovascular risk factors, including the mean arterial pressure and pulse pressure.     

Inverse relationship between ambulatory arterial stiffness index and glomerular filtration rate in arterial hypertension

BACKGROUND: Arterial stiffness and mild-to-moderate renal dysfunction are predictors of cardiovascular (CV) morbidity and mortality. Recently, the ambulatory arterial stiffness index (AASI) has been proposed as a surrogate index of arterial stiffness. It has been associated with an enhanced risk of stroke. The aim of our study was to assess the relationship between AASI and glomerular filtration rate (GFR) in a group of hypertensive patients with no CV complications. METHODS: A total of 143 untreated hypertensive subjects (mean age: 44 +/- 12 years; men 57%), with serum creatinine <1.5 mg/dl, were enrolled. AASI was calculated as one minus the regression slope of diastolic on systolic blood pressure (BP) obtained by individual 24-h BP recordings. GFR was computed from the scintigraphic determination of the technetium-99m diethylenetriaminepentaacetic acid uptake within the kidneys, by the Gates' method. RESULTS: Hypertensive patients with AASI above the median value (n = 71) had lower GFR than those with AASI below the median (n = 72) (98.3 +/- 31 vs. 122.4 +/- 32 ml/min/1.73 m(2); P < 0.001). This difference held even after adjustment for age and gender. The linear regression analysis disclosed a significant inverse correlation between GFR and AASI (r = -0.30; P < 0.001), that was replicated (beta = -0.19; P = 0.02) in a multiple regression model including, as independent variables (besides AASI), age, gender, high-density lipoprotein cholesterol, body mass index, 24-h pulse pressure (PP) and nocturnal reduction in BP. CONCLUSIONS: AASI is inversely related to GFR in arterial hypertension. This may help to explain the increased CV risk associated with mild-to-moderate renal dysfunction.     

Association of renal function with the ambulatory arterial stiffness index and pulse pressure in hypertensive patients

Arterial stiffness exemplified by the ambulatory arterial stiffness index (AASI) and pulse pressure (PP) predicts cardiovascular morbidity and mortality. The present cross-sectional study assessed the association of renal function with AASI and 24-h PP in hypertensive inpatients. Subjects included 948 hypertensive inpatients with drug treatment (mean age, 53.3 years; male, 67.1%). The AASI was defined as 1 minus the regression slope of diastolic over systolic blood pressure readings obtained from 24-h recordings. Renal function was evaluated by serum creatinine and urinary albumin excretion was expressed by the urinary albumin-to-urinary creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease formula and chronic kidney disease-epidemiology collaboration formula. As AASI and 24-h PP increased, serum creatinine concentrations and ACR increased, and eGFR decreased. Multiple linear regression showed that AASI and 24-h PP were associated with eGFR-EPI (B=-12.00, P=0.001 vs. B=-0.14, P=0.002) and ACR (B=0.56, P=0.004 vs. B=0.01, P=0.017) independent of other cardiovascular risk factors. After additional adjustment for 24-h PP, the association of AASI with eGFR-EPI had borderline significance (P=0.053), whereas the significant associations of 24-h PP with serum creatinine and ACR persisted (P=0.009 and P=0.006) after adjusting for confounding factors and AASI. Multiple logistic regression analysis showed that each s.d. increase in 24-h PP (that is, 13?mm?Hg) was associated with a higher risk of suffering from microalbuminuria (MA) by 39% (P=0.038) after additional adjustment for AASI. In conclusion, AASI is more closely associated with eGFR compared with 24-h PP in hypertensive inpatients. However, for MA 24-h PP is a better predictor.     

Association of ambulatory arterial stiffness index and brachial pulse pressure is restricted to dippers

BACKGROUND: The ambulatory arterial stiffness index (AASI) is a new index that reflects the dynamic relation between diastolic and systolic blood pressure through the circadian blood pressure rhythm. It was the aim of this study to investigate the association between AASI, dipping status and pulse pressure as a classical indicator of arterial stiffness in normotensive and hypertensive subjects. METHODS: One hundred and twelve individuals were evaluated for a kidney donation to a relative at the University Hospital Essen, Germany. In this context routine 24-h ambulatory blood pressure measurements were performed. A nocturnal reduction in diastolic blood pressure of >10% was defined as 'dipping'. We determined the diurnal and nocturnal blood pressure and brachial pulse pressure values and computed AASI for each participant. RESULTS: AASI was a strong predictor for diastolic and systolic nocturnal blood pressure fall (r = -0.55 and -0.48, respectively; P < 0.001). Additionally, AASI predicted the status of 'dipping/nondipping'. 'Dippers' showed significantly lower AASI than 'nondippers' in both normotensive and hypertensive subjects. Dippers, but not nondippers, demonstrated an association between AASI and brachial pulse pressure. DISCUSSION: AASI is strongly correlated with nocturnal blood pressure fall and is increased in nondipping independent of blood pressure. The role of AASI as a potential marker for arterial stiffness depends, in this study, on the characterization of the dipping status.     

Ambulatory arterial stiffness index derived from 24-hour ambulatory blood pressure monitoring

We hypothesized that 1 minus the slope of diastolic on systolic pressure during 24-hour ambulatory monitoring (ambulatory arterial stiffness index [AASI]) might reflect arterial stiffness. We compared AASI with established measures of arterial stiffness and studied its distribution in Chinese and European populations. We used 90207 SpaceLabs monitors and the SphygmoCor device to measure AASI, central and peripheral pulse pressures, the central (CAIx) and peripheral (PAIx) systolic augmentation indexes, and aortic pulse wave velocity. In 166 volunteers, the correlation coefficient between AASI and pulse wave velocity was 0.51 (P<0.0001). In 348 randomly recruited Chinese subjects, AASI correlated (P<0.0001) with CAIx (r=0.48), PAIx (r=0.50), and central pulse pressure (r=0.50). AASI increased with age and mean arterial pressure but decreased with body height. Both before and after adjustment for arterial wave reflections by considering height and heart rate as covariates, AASI correlated more (P<0.0001) closely with CAIx and PAIx than 24-hour pulse pressure. Among normotensive subjects, the 95th percentile of AASI was 0.55 in Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of AASI in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In conclusion, AASI is a new index of arterial stiffness that can be easily measured under ambulatory conditions. Pending additional validation in outcome studies, normal values of AASI are probably <0.50 and 0.70 in young and older subjects, respectively.     

Ambulatory arterial stiffness index is not a specific marker of reduced arterial compliance

Ambulatory arterial stiffness index (AASI), a measure based on the relative behavior of 24-hour systolic and diastolic blood pressure (BP), has been suggested as a marker of arterial stiffness and a predictor of cardiovascular mortality. However, a narrow range of diastolic BP values over the 24 hours tends to flatten the regression slope and to artificially increase AASI. We explored the possible influence of different ranges of 24-hour diastolic BP fluctuations, such as those related to nocturnal BP fall, on AASI, and on its relationship with target organ damage. In 515 untreated hypertensive patients, AASI was directly related to age (r=0.30) and 24-hour systolic BP (r=0.20), whereas it was inversely related with nocturnal systolic and diastolic BP reduction (r=-0.28 and -0.46, respectively; all P<0.001). A direct relationship was found between AASI and left ventricular mass index (r=0.17; P<0.001), but this relation was no longer significant after adjustment for age, sex, body mass index, daytime systolic BP, and day-night systolic BP reduction (all P<0.05). AASI was directly related to carotid-femoral pulse wave velocity, an intrinsic measure of aortic stiffness (r=0.28; P<0.001), but no independent relation was found in a multiple linear regression. Our conclusions are as follows: (1) AASI is strongly dependent on the degree of nocturnal BP fall in hypertensive patients; (2) there is no significant relation between AASI and left ventricular mass after proper adjustment for confounders; and (3) the relation between AASI and a widely accepted measure of aortic stiffness, such as pulse wave velocity, is weak and importantly affected by other factors.