| BackgroundHypertension is the most prevalent cardiovascular diseases. It is one of the primary riskfactors for target organ damage, such as myocardial infarction, kidney failure and stroke.Mean blood pressure (BP) is widely recommended to diagnose and monitor hypertension indaily practice and all major clinical guidelines. Good control of the mean systolic (S)BP anddiastolic (D)BP level are generally considered to be a crucial component in the managementof cardiovascular diseases. Yet, evidence has accumulated to show that the protective effectof antihypertensive treatment depends not only on reductions in average BP but also on howstable on-treatment BP control on the long term in recent years. Evidences demonstrated thatvisit-to-visit variability creates challenges to high blood pressure control and was independentassociated with increased all-cause mortality in hypertensive patients. Prevention and controlof hypertension should not only pay attention to the antihypertensive treatment, but also focuson identification of target organ damage. Antihypertensive therapy has developed frommonotherapy to combinational therapy. Choosing the right combinational antihypertensivetreatment can be more benefit for hypertensive patients. However, the effect ofantihypertensive treatment and visit-to-visit blood pressure variability on the target organdamage, especially subclinical target organ damage, did not investigated in much detail.Pulse wave analysis measurement, a reliable non-invasively method using applanationtonometry, can provide important information about several arterial stiffness and hemodynamic parameters including carotid-radial pulse wave velocity (crPWV), aorticaugmentation index (Aix), and sub-endocardial viability ratio (SEVR).Carotid artery IMT, carotid artery stiffness index β, and flow-mediated dilation (FMD) ofthe brachial artery, evaluated noninvasively using high-resolution ultrasound, is a widelyaccepted clinical tool for indicating subclinical atherosclerosis and peripheral endothelialfunctions.From these standpoints, we hypothesized that antihypertensive treatment and visit-to-visitblood pressure variability might be also associated with arterial stiffness and endothelialfunction. Besides lowering BP level, reduce the visit-to-visit blood pressure variability maybeameliorate the progression of arterial stiffness, endothelial function disfunction andmyocardial perfusion deficiency in on-treated hypertensive patients. This hypothesis may bebenefit for hypertensive patients and reduce the cardiovascular morbidity and mortality.Objective1) To investigate the effect of antihypertensive treatment on the arterial stiffness, endothelialfunction and myocardial perfusion;2) To investigate the effect of the different combination antihypertensive therapy on thearterial stiffness, endothelial function and myocardial perfusion;3) To investigate the changes of the arterial stiffness, endothelial function and myocardialperfusion in different level of visit-to-visit blood pressure variability;4) To investigate the effect of visit-to-visit blood pressure variability on the arterial stiffness,endothelial function and myocardial perfusion.MethodsThe basic information was collected in a total of169essential hypertensive patients. Themean age was54.04±7.10years (range40-79years). All participants were randomlyassigned into two antihypertensive treatment arms: amlodipine plus amiloride/hydrochlorothiazide or amlodipine plus telmisartan. Follow-up visit was performed at3-month intervals. Clinic BP measurements were performed at each visit. Pulse wave analysismeasurements, high-resolution ultrasound measurements and clinical laboratorymeasurements were conducted at baseline and end of trial. The study duration was four years.Visit-to-visit blood pressure variability was calculated by the standard deviation (SD) of serially measured systolic blood pressure (SBP). According to the tertile of SD of SBP, allpatients were divided into three groups, namely, low SD of SBP group (low group), middleSD of SBP group (middle group), and high SD of SBP group (high group).Results1) Compared to baseline, crPWV, Aix, Aix@HR75, stiffness index β, and ET-1werestatistically decreased (P <0.05); FMD, NO, and SEVR were statistically increased in overall(P <0.05).2) crPWV, Aix, FMD and ET-1in subjects who used amlodipine plus amiloride/hydrochlorothiazide were significantly higher than that in subjects who used amlodipine plustelmisartan (P <0.05).3) Compared with baseline, crPWV was significantly decreased in overall and three groupsclassified by tertile of SD of SBP (P <0.01). Median (inter-quartile range, IQR) change rateof crPWV was-6.42(-7.75,-4.99)%,-5.60(-6.95,-2.74)%, and-1.81(-3.77,0.24)%infrom low group to high group, respectively. The decreased rate of stiffness index β in lowergroups was statistically greater than in higher group (P <0.01);Compared with baseline, Aix and Aix@HR75were markedly reduced in overall and eachgroup (P <0.01). The reduced ratios of Aix and Aix@HR75in lower groups werestatistically greater than in higher groups. There were significant differences between any twogroups (P <0.01). Median (IQR) change rate of Aix was-15.38(-18.60,-12.50)%for lowgroup;-11.54(-14.29,-9.68)%for middle group;-8.88(-10.83,-6.25)%for high group.Median (IQR) change rate of Aix@HR75was-16.67(-18.45,-13.71)%for low group;-14.29(-15.62,-11.33)%for middle group;-10.71(-12.80,-7.69)%for high group；Compared to baseline, IMT elevated in overall and high group, decreased in low group (P<0.01), and was no significant change in middle group (P>0.05). There were significantdifferences between any two groups (P <0.01). Median (IQR) change ratio of IMT was-0.70(-2.26,0.72)%in low group,0.69(-1.09,2.37)%in middle group, and2.98(1.39,4.70)%in high group;Compared with baseline, stiffness index β was significantly decreased in overall and threegroups (P <0.01). The decreased ratio of stiffness index β in lower groups was statisticallygreater than in higher group (P <0.01). Median (IQR) change ratio of stiffness index β was -11.68(-14.25,-8.06)%,-8.00(-10.71,-4.00)%, and-3.00(-6.00,-0.07)%in from lowgroup to high group, respectively;Compared to baseline, FMD and NO were statistically increased in overall and threegroups (P <0.01). The increased ratios of FMD and NO in lower groups were statisticallygreater than in higher group (P <0.01). Median (IQR) change ratio of FMD was8.50(6.57,9.51)%,6.30(4.80,8.32)%, and2.47(0.56,4.63)%, NO was25.54(21.73,30.45)%,20.88(16.25,25.48)%,12.92(7.45,19.69)%in from low group to high group, respectively;Compared to baseline, ET-1was statistically decreased in overall and three groups (P <0.01). The decreased ratio of ET-1, it was markedly lower in high group than in low andmiddle group (P <0.01); there was no difference between low group and middle group (P>0.05). Median (IQR) change ratio of ET-1was-8.59(-11.00,-5.95)%,-7.00(-10.18,-4.00)%,-2.00(-5.00,0.40)%in from low group to high group, respectively;Compared with baseline, SEVR was obviously increased in overall and each group (P <0.01). The increased ratio of SEVR in lower groups were statistically greater than in highergroups and there were significant differences between any two groups (P <0.01). TheMedian (IQR) of increased percentage ratio in SEVR was23.29(20.72,26.40)%for lowgroup;18.84(15.18,22.52)%for middle group;12.02(8.01,15.59)%for high group.4) Change ratios of crPWV, Aix, Aix@HR75, IMT, stiffness index β, and ET-1weresignificant positively correlated with SD of SBP, CV of SBP, Maximum SBP, delta SBP, andmean SBP (P <0.01). Yet, change ratios of FMD, NO and SEVR were significant negativelycorrelated with SD of SBP, CV of SBP, Maximum SBP, delta SBP, and mean SBP (P <0.01).5) Stepwise multiple regression analysis was performed to examine the relationships ofchange ratios of crPWV, Aix, Aix@HR75, IMT, stiffness index β, ET-1, FMD, NO andSEVR with visit-to-visit variability of blood pressure. For change ratio of crPWV, there werestatistically significant results for SD, CV of SBP, baseline SBP and smoking. For changeratio of Aix, significant results were SD and CV of SBP, baseline SBP. For change ratio ofAix@HR75, significant results were SD and CV of SBP, and baseline TCHO. For changeratio of IMT, there were statistical results for SD and CV of SBP and mean SBP. For changeratio of stiffness index β, there were significant results for SD and CV of SBP, mean SBP, and change ratio of LDL-c. For change ratio of FMD, there were significant results for SDand CV of SBP, mean SBP, change ratio of TG, and baseline LDL-c. For change ratio of NO,there were significant results for SD and CV of SBP, and delta SBP. For change ratio of ET-1,there were significant results for SD and CV of SBP, mean SBP, change ratio of TG, andstatin treatment. For change ratio of SEVR, significant results were SD and CV of SBP,smoking and baseline HDL-c. However, most importantly, SD and CV of SBP were alwaysstatistically associated with change ratios of crPWV, Aix, Aix@HR75, IMT, stiffness index β,FMD, NO, ET-1and SEVR.ConclusionAntihypertensive treatment could postpone the progress of arterial stiffness, improvevascular compliance and the endothelial function, and increase the the myocardial perfusionusing either of the two antihypertensive regiments, namely, amlodipine plusamiloride/hydrochlorothiazide or amlodipine plus telmisartan. The effect of amlodipine plustelmisartan was greater than that of amlodipine plus amiloride/hydrochlorothiazide.Visit-to-visit variability of blood pressure, especially variability of systolic blood pressure,was closely associated with arterial stiffness, endothelial function disfunction and myocardialperfusion deficiency. Excessive visit-to-visit blood pressure variability maybe reduce thebenefit of antihypertensive treatment in hypertensive patients. |
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