a portion of the arterial pressure wave travelling towards the extremities is reflected back from peripheral impedance points . in healthy individuals , the reflected wave returns to the aorta during diastole . with age and in the presence of vascular disease ,
arterial compliance decreases , and the arteries become stiff , thereby reducing the transit time for the incident and reflected waves .
consequently , the reflected wave arrives at the aorta during systole of the same cardiac cycle augmenting the central blood pressures .  
this augmentation of central pressure can be quantified by augmentation index ( aix ) , defined as the percentage of the central pulse pressure attributed to the reflected pulse wave .  
aix has been shown to be associated with cardiovascular risk , predicts the presence or absence of coronary artery disease ( cad ) [ 2 , 3 ] , and has been shown to be an independent predictor of cardiovascular events and all - cause mortality in select patient populations [ 4 , 5 ] .
conventionally , aix is obtained from pressure waveforms via applanation tonometry of the carotid or radial arteries .
recently , it has been demonstrated that aix can be measured from digital pulse wave volumes by peripheral arterial tonometry ( pat ) [ 6 , 7 ] , and that it is associated with ventricular - vascular coupling .
the value obtained by aix derived by pat correlates with that obtained by conventional radial applanation tonometry ; however , they can not be used interchangeably since the actual values do not match since they are obtained from two distinct vascular beds via two different methods .
therefore , we sought to evaluate the association between pat - derived aix and cardiovascular risk factors ( crfs ) and/or cad .

 study 1146 patients recruited from the cardiology clinic at tufts medical center in boston were enrolled in the study .
subjects were instructed to fast overnight and to refrain from smoking , caffeine , or alcohol on the day of testing .
146 patients recruited from the cardiology clinic at tufts medical center in boston were enrolled in the study .
subjects were instructed to fast overnight and to refrain from smoking , caffeine , or alcohol on the day of testing .
study 240 consecutive patients undergoing clinically indicated nonemergent left heart catheterization were retrospectively identified for inclusion into this study . as part of the standard catheterization protocol
, blood pressures were measured within the femoral artery , ascending aorta , and the left ventricle using a 6-french end hole fluid - filled catheter and a pressure manometer prior to injection of any contrast agent .
pressures within the ascending aorta were considered as the central blood pressure ( cbp ) in the study.the presence or absence of the following cardiovascular risk factors was assessed in all the subjects from both substudies : male gender , hypertension ( systolic blood pressure > 140  mmhg , diastolic blood pressure > 90  mmhg , or being on an antihypertensive medication ) , hyperlipidemia ( serum cholesterol > 220  mg / dl or taking lipid - lowering medication ) , diabetes mellitus ( fasting blood glucose > 140  mg / dl or on oral hypoglycemics or insulin ) , family history of cad ( first - or second - degree relatives with premature cad ) , postmenopausal women , and smoking ( having smoked at least five times per day within last month ) .
cad was defined as the presence of ischemia or infarction on single - photon emission - computed tomographic ( spect ) nuclear myocardial perfusion imaging or > 50% stenosis of an epicardial coronary artery by angiography.patients with moderate to severe heart failure ( nyha class iii - iv , lvef < 35 ) , hemodynamic instability , peripheral arterial disease ( ankle - brachial index < 0.9 ) , and finger deformities were excluded from the study .
40 consecutive patients undergoing clinically indicated nonemergent left heart catheterization were retrospectively identified for inclusion into this study . as part of the standard catheterization protocol , blood pressures were measured within the femoral artery , ascending aorta , and the left ventricle using a 6-french end hole fluid - filled catheter and a pressure manometer prior to injection of any contrast agent .
pressures within the ascending aorta were considered as the central blood pressure ( cbp ) in the study . the presence or absence of the following cardiovascular risk factors
was assessed in all the subjects from both substudies : male gender , hypertension ( systolic blood pressure > 140  mmhg , diastolic blood pressure > 90  mmhg , or being on an antihypertensive medication ) , hyperlipidemia ( serum cholesterol > 220  mg / dl or taking lipid - lowering medication ) , diabetes mellitus ( fasting blood glucose > 140  mg / dl or on oral hypoglycemics or insulin ) , family history of cad ( first - or second - degree relatives with premature cad ) , postmenopausal women , and smoking ( having smoked at least five times per day within last month ) .
cad was defined as the presence of ischemia or infarction on single - photon emission - computed tomographic ( spect ) nuclear myocardial perfusion imaging or > 50% stenosis of an epicardial coronary artery by angiography .
patients with moderate to severe heart failure ( nyha class iii - iv , lvef < 35 ) , hemodynamic instability , peripheral arterial disease ( ankle - brachial index < 0.9 ) , and finger deformities were excluded from the study .
prior to collecting vascular measures , all study subjects rested in a quiet dark room for a period of 10 minutes .
post - acclimatization , the vascular data was recorded by pat ( endopat2000 , itamar medical ltd , caesarea , israel ) for a period of 5 minutes with the patient in supine position . the procedure for obtaining aix is essentially the same as described in previous reports .
the probes , lined by inflatable balloons , are connected to isolated volume reservoirs within the machine , which buffer pressure changes and provide a uniform pressure field .
also , the counter - pressure imparted by the balloon prevents distal venous distension and blood pooling , which might induce a local venoarteriolar vasoconstriction reflex [ 10 , 11 ] .
the pat system is designed to unload arterial wall tension and increase the range of arterial wall motion without inducing potentially confounding vasomotor changes .
pressure sensors within this cap capture beat - by - beat finger pulse wave amplitude ( pwa ) which is then filtered , amplified , and graphically displayed on a computer screen .
a computerized algorithm has been generated to automatically identify peak pressures and inflection point as previously described by kelly et al .   and
pat - aix is calculated by averaging the pwa data over an epoch of 3.5 minutes and is calculated by the following formula :    pat - aix = ( p2  p1 )  100  /  p1(% ) , where p1 =   pulse pressure and p2 =   pressure corresponding to the inflection point .
cardiac risk factors ( age > 45  yrs in men and > 55  yrs in women , male gender , menopause , hypertension , hypercholesterolemia , cigarette smoking , diabetes mellitus and family history of cad ) were tabulated as nominal variables . depending upon the total number of crfs per patient , the study population was divided into tertiles , including those with <3 crfs , 35 crfs , and > 5 crfs .
analysis of variance ( for parametric data ) with scheffe post hoc testing was performed to assess difference in continuous variables between groups .  
binary logistic regression analysis ( 0.05 to enter , 0.10 to remove ) was used to evaluate for relationship between aix and cad and to evaluate for potential confounders including age , gender , height , heart rate , presence of hypertension , hypercholesterolemia , diabetes mellitus , tobacco use , and family history of cad . a receiver operator characteristic (
186 subjects ( 129 men , 57 women ) with an average age of 59  1 years were enrolled .
55% patients had cad , 52% patients had hypertension , 24% were diabetic , 58% had hypercholesterolemia , 44% were smokers , and 35% had family history of cad .
a significant association was observed between pat - aix and age ( r = 0.265 , p <
< .0001 ) , mean arterial pressure ( r = 0.170 , p < .045 ) , and pulse pressure ( r = 0.198 , p = .012 ) .  
the relationship between pat - aix and age best fitted a quadratic regression model ( p = .01 ) .  
aix was not associated with diabetes mellitus , smoking status , or family history of cad .
similarly , no significant correlation was observed between pat - aix and systolic blood pressure , gender , height , and lipids .
stepwise multiple regression analysis identified age , heart rate , diastolic blood pressure , weight , and cigarette smoking as predictors of pat - aix .
analysis of variance ( scheffe post hoc testing ) revealed a significant difference in aix between patients with <3 crfs ( 5.15  2.09% ) and those having > 5 crfs ( 5.65  2.55% , p = .02 , figure 1 ) .  
pat - aix in patients with 35 cardiac risk factors was not significantly different than in those with either <3 or > 5 crfs .
pat - aix was significantly higher amongst cad+ patients ( 1.01  1.6% ) as compared to cad patients ( 5.46  1.7% , p = .008 , figure 2 ) . to examine the ability of pat - aix to predict cad+ , the area under the roc curve yielded a value of 0.604 ( p
< .01 , figure 3 ) . after dividing the study population into tertiles based on the pat - aix values , there was a stepwise increase in prevalence of cad with an increase in pat - aix ( p < .05 , figure 4 ) .
however , after adjusting for potential confounders , including age , sex , heart rate , smoking , diabetes , hypertension , and hypercholesterolemia , pat - aix was not significantly different between these two groups .
pat - aix correlated with aortic systolic pressure ( r = 0.480 , p = .002 , figure 5 ) , and aortic pulse pressures ( r = 0.455 , p = .004 , figure 6 ) .    after adjusting for age , height , and heart rate ,
aix remained a significant predictor of aortic systolic pressure (  = 0.449 , 95% ci 0.1870.712 , p = .001 ) and aortic pulse pressure (  = 0.424 , 95% ci 0.0420.805 , p = .0031 ) .
analysis focusing on effects of medications on peripheral augmentation index revealed a significant association between pat - aix with beta - blockers ( p = .018 ) and ace inhibitors ( p = .03 ) .
there was no association between pat - aix and calcium blockers , angiotensinogen receptor blockers , nitrates , statins , digoxin , diuretics , oral hypoglycemics , insulin , thyroid hormone supplements , antidepressants , and steroids .
our study was undertaken to evaluate the association of peripheral aix and cardiovascular risk factors .
similar to what has been found with aix derived from applanation tonometry , pat - derived aix correlates with age , weight , bmi , heart rate , diastolic blood pressure , pulse pressure , and mean arterial pressure .
previous studies have noted that the increase in aix with age is not linear .   in alignment with previously published data , a quadratic model best illustrates the relationship between age and pat - aix .  
it has been observed that aix measured by conventional applanation tonometry begins to plateau at the age of 60 years .
impedance matching may differ in the hand circulation versus the aorta as there may not be changes in digital endothelial function with aging .  
patients with > 5 crfs had a significantly higher pat - aix as compared with those having only a few crfs .   similarly , when the prevalence of cad was assessed across tertiles of pat - aix , it was noted that patients in the highest tertile had a significantly higher prevalence of cad as compared to those in the lower tertiles .  
pat - aix was able to discern the presence or absence of cad amongst a heterogeneous patient population with varying in cardiovascular risk .
the classification performance of peripheral aix was assessed by generating a receiver - operated characteristic curve which revealed an auc of 0.604 . however , after adjusting for traditional risk factors such as age , sex , heart rate , height , weight , hypertension , diabetes mellitus , hypercholesterolemia , smoking , and family history of premature coronary heart disease , aix lost its statistical significance .
thus , pat - derived aix is not an independent predictor of cad in this population .   
the importance of assessing central blood pressure lies in the fact that traditionally measured brachial artery blood pressure is often a poor representation of actual central pressures .   due to pressure wave amplification
, the brachial systolic pressure can be up to 20  mmhg higher than the aortic systolic pressure [ 1517 ] . since the left ventricle works against pressures within the ascending aorta , aortic pressures play a significant role in the pathophysiology of cardiac disease .
as such , aortic systolic and pulse pressures can be considered as novel cardiovascular risk factors since they are predictors of cardiovascular events , target organ damage , and mortality .  
compared to brachial systolic and pulse pressure , aortic pulse pressure appears to be a better predictor of the presence and extent of coronary atherosclerosis [ 19 , 20 ] and restenosis after coronary intervention .
furthermore , a reduction in central blood pressure results in a reduction in cardiac hypertrophy , vascular thickness , and adverse cardiac events [ 2224 ] .
for example , a 10  mmhg reduction in aortic pulse pressure has been shown to translate into a 1315% reduction in cv events and all - cause mortality [ 25 , 26 ] . in alignment with data published by munir et al .
, our study reveals that aix measured by pat also closely correlates with central aortic blood pressures .  
we do acknowledge certain limitations in this study . while it has been suggested that arterial stiffness and augmented pressure from wave reflections make the most significant contributions to the digital volume pulse inflection point , vascular correlates or pat - aix remain unexplored .
it is true that spect imaging results do not always correlate with severity of coronary artery stenosis .
however , we chose stress testing because it provides physiologic information regarding ischemia and prior infarction .
while spect imaging does not confer 100% sensitivity and specificity , this technique is a reliable , noninvasive assessment of myocardial ischemia / infarction . in substudy 2
, central pressures were obtained using conventional fluid - filled catheters , rather than high - fidelity pressure transducers .
in addition , aix was not obtained simultaneously during catheterization when actual central pressure values were obtained .
pat has been under investigation over recent years as a technique for assessment of vascular endothelial function .
the present data suggest that this simple , noninvasive technique may also provide information regarding augmentation index .
our findings suggest that finger - derived aix may be comparable to applanation tonometry for measurement of augmentation index and evaluation of cardiovascular risk .
however , as observed by haller et al . , although the values of aix obtained by pat correlate with that obtained by conventional radial applanation tonometry , they can not be used interchangeably since the actual numbers do not match .
further validation is warranted in large scale studies comparing pat - aix with that obtained by the current gold standard radial applanation tonometry in a wider patient population .
 
 background . augmentation index ( aix ) is traditionally obtained from pressure waveforms via arterial applanation tonometry . 
 we sought to evaluate the association between 
 aix obtained from peripheral arterial tonometry ( pat ) with cardiovascular risk factors ( crf ) and coronary artery disease ( cad ) . 
  
 methods . 
 186 patients were enrolled in the study . the presence or absence of crfs and cad 
 was assessed in each subject . 
 aix was calculated by an automated algorithm averaging pulse wave amplitude data obtained via pat . 
 central blood pressures were assessed in a subset of patients undergoing clinically indicated cardiac catheterization . results . 
 an association was observed between aix and age , heart rate , systolic blood pressure , mean arterial pressure , pulse pressure , body weight and body mass index . 
 aix was significantly lower in patients with <3 
  crfs compared to those with > 5 crfs ( p = .02 ) . 
 cad+ patients had significantly higher aix compared to cad patients ( p = .008 ) . 
 area under the roc curve was 0.604 ( p < .01 ) .   in patients undergoing cardiac catheterization , 
 after adjusting for age , height and heart rate , aix was a significant predictor of aortic systolic and pulse pressures ( p < .05 )   conclusion . 
 aix derived from pat correlates with cardiac risk factors and cad . 
 it may be a useful measure of assessing overall risk for coronary artery disease . 
 
1. Introduction
2. Methods
3. Results
4. Discussion
5. Conclusion