|Year : 2018 | Volume
| Issue : 3 | Page : 102-107
Central aortic pressure indices and cardiovascular risk factors: Demographic, clinical, and prognostic characterization
Rajesh Gopalan Nair1, Shreetal Rajan Nair2, Vinayakumar D1, Kader Muneer1, Haridasan V1, Dolly Mathew1, Biju George3, Krishnan MN1, Sajeev CG1
1 Department of Cardiology, Government Medical College, Kozhikode, Kerala, India
2 Department of Centre for Heart and Vascular Care, Meitra Hospital, Kozhikode, Kerala, India
3 Department of Community Medicine, Government Medical College, Kozhikode, Kerala, India
|Date of Web Publication||12-Sep-2018|
Dr. Shreetal Rajan Nair
Centre for Heart and Vascular Care, Meitra Hospital, Kozhikode, Kerala
Source of Support: None, Conflict of Interest: None
Objectives: The primary objective of the study was to assess the association between central aortic blood pressure indices and coronary artery disease (CAD) in patients undergoing elective angiography and the secondary objective was to study whether any association exists between central aortic pressure indices and the incidence of major adverse cardiovascular events (MACE) in the same patients during a 6-month follow-up period.
Methods: We conducted a prospective observational study in consecutive patients undergoing coronary angiography. Central and peripheral pressures were invasively recorded and CAD was classified into obstructive and nonobstructive group. CAD severity was graded using the Gensini score and patients were divided into tertiles. Patients were followed up, and the role of central aortic pressure indices in the prediction of cardiovascular events was analyzed.
Results: A total of 623 patients were enrolled. Central pulsatility was found to be most closely associated with severity of CAD by univariate analysis, with age, sex, and smoking status being important predictors of pulsatility. A positive correlation was found between the central and peripheral mean and pulse pressures. No significant association was noted between the central aortic pressures and MACE on short-term follow-up.
Conclusions: Of the various central aortic pressure indices studied, central pulsatility was found to be most closely associated with the severity of CAD.
Keywords: Central aortic pressure, coronary artery disease, Gensini score, pulsatility, pulse pressure
|How to cite this article:|
Nair RG, Nair SR, Vinayakumar, Muneer K, Haridasan, Mathew D, George B, MN K, CG S. Central aortic pressure indices and cardiovascular risk factors: Demographic, clinical, and prognostic characterization. Heart India 2018;6:102-7
|How to cite this URL:|
Nair RG, Nair SR, Vinayakumar, Muneer K, Haridasan, Mathew D, George B, MN K, CG S. Central aortic pressure indices and cardiovascular risk factors: Demographic, clinical, and prognostic characterization. Heart India [serial online] 2018 [cited 2018 Dec 15];6:102-7. Available from: http://www.heartindia.net/text.asp?2018/6/3/102/241068
| Introduction|| |
Blood pressure (BP) assessment is an inevitable part of the evaluation of cardiovascular disease (CVD) and can be measured both invasively and noninvasively. Conventionally, bood pressure is are measured noninvasively in the peripheral arteries. However, it has its own limitations, with invasive monitoring providing a more accurate assessment when compared to the noninvasive method. The pulsatile component of BP (pulse pressure [PP]) has been found to be more important in the prediction of future cardiovascular adverse events in comparison to the steady-state component (mean pressure). Recently, central BP and arterial stiffness have been found to be more relevant pathophysiologically than peripheral pressures in the pathogenesis of CVD and are areas of intense ongoing research.,,,, Central BP indices are found to be independently associated with subclinical CVD and adverse events in the general population as well as in various disease states.,,,,, There is a real paucity of data on the Indian population on central BP and cardiovascular risk and hence the relevance of the study.
| Methods|| |
The primary objective of the study was to assess the association between central aortic BP indices and coronary artery disease (CAD) in patients undergoing elective angiography and the secondary objective was to study whether any association exists between central aortic pressure indices and the incidence of major adverse cardiovascular events (MACE; defined as acute coronary syndrome [ACS], stroke, and urgent coronary revascularization due to ACS or death) in the same patients during a 6-month follow-up period. The study was a prospective observational study conducted in consecutive patients undergoing elective coronary angiography for the diagnosis of CAD. The study was divided into two parts – the initial 6 months being the enrollment phase and the latter 6 months being the follow-up phase. The inclusion criteria were patients undergoing elective angiography for diagnosis of CAD and aged >18 years. The exclusion criteria were patients with acute myocardial infarction, unstable angina, or thromboembolism in the preceding 3 months; more than mild valvular heart disease; renal impairment with serum creatinine >1.5 mg%; unable to obtain a full study of the coronary arteries; peripheral vascular occlusive disease; postcoronary artery bypass graft (CABG) surgery; heart rate <50/min and >120/min and other arrhythmias; contraindications for coronary angiography; and unable to provide written informed consent. After obtaining approval from the institutional ethics committee, the study was commenced. A full demographic and clinical characterization of the patients was performed at the study entry. Data recorded included age, height, weight, noninvasive BP (NIBP), ejection fraction (measured by echocardiography in the preceding 1 month of the date of cardiac catheterization), smoking status, previous myocardial infarction, history of peripheral vascular disease, congestive heart failure, diabetes mellitus (DM), hypercholesterolemia, stroke, or revascularization procedures (CABG or percutaneous coronary intervention). The indication for cardiac catheterization and the medications that patients were receiving at that time was also recorded. NIBP measurement was done using the Omron automatic BP monitoring apparatus, and both right and left brachial BP values were recorded as an average of 3 BP readings taken 3 min apart in the recumbent position at the time of cardiac catheterization. For invasive BP measurement and pulse waveform analysis, a low-compliance, fluid-filled system was used in the study and all the invasive BP measurements were done after ensuring proper zeroing, calibration, and balancing. Only waveforms that were technically adequate (free from artifacts and optimally damped) were included in the study. Peripheral invasive BP measurement was done after obtaining femoral vascular access, and the pressures were recorded from 7F sheath sidearm. Central aortic pressure waveform was recorded with a Judkins 6F coronary catheter positioned just above the aortic sinus in the ascending aorta. The various pressure indices studied were systolic BP (SBP) and diastolic BP (DBP) by direct measurements and PP (SBP − DBP), mean arterial pressure (MAP = DBP + PP/3), pulsatility (PP/MAP), pulsatility index (PP/DBP), absolute BP amplification (peripheral PP − central PP), relative BP amplification (peripheral PP/central PP), and PP amplification (PPA = [peripheral PP − central PP/central PP] × 100) by indirect derived calculations. Pulsatility and pulsatility index were calculated in the central aorta only as they are relevant only in the central arteries. Hypertension was defined as a high brachial BP (SBP ≥140 mmHg or DBP ≥90 mmHg) in three consecutive readings at rest or prescription of a BP-lowering drug for high BP. Coronary angiography was performed and images of the coronary vasculature were obtained in routine standardized projections. CAD was classified using the Gensini score, and patients were grouped into tertiles based on the score. Patients were also classified into two groups: obstructive CAD (the presence of at least one >50% reduction of intraluminal diameter on any of the major epicardial arteries or the major side branches) and nonobstructive (all cases other than obstructive CAD). A major side branch was defined as any branch arising from the proximal or mid segment of a major epicardial artery and having a diameter of 2 mm or more. The patients were followed up for 6 months by telephone calls and/or outpatient visits, and any occurrence of MACE was recorded. The primary outcome studied was the composite of unstable angina, acute myocardial infarction, stroke, or death from any cause. The secondary outcomes studied were the individual components of the primary outcome.
Analysis of data from previous studies showed that a minimum sample size of 576 was needed for the study to be adequately powered (80%). Categorical variables were studied using Chi-square and analysis of variance (ANOVA) test and continuous variables using Student's t-test. Post hoc analysis of various groups analyzed by ANOVA test was also performed. Univariate analysis was first performed followed by multivariate analysis of the variables that were found to be significant in univariate analysis. Multivariate logistic regression was done using Cox and Snell R-square model. SPSS 16.0 (SPPS Inc., Chicago, USA) software was used for analysis and P < 0.05 was considered statistically significant.
| Results|| |
The study was conducted in a tertiary care center in Kerala state of India from April 2014 to March 2015. A total of 940 consecutive patients undergoing coronary angiography were screened, from which 623 patients were enrolled finally after applying the study criteria. The major exclusions were primary percutaneous transluminal coronary angioplasty (n = 160), recent ACS (n = 51), peripheral vascular disease (n = 68), valvular heart disease (n = 16), raised serum creatinine >1.5 mg% (n = 10), technically incorrect tracings (n = 6), atrial fibrillation (n = 4), and unable to perform complete angiography of the coronaries (n = 2).
Males accounted for 67.3% of the total study patients. A history of smoking was present in 32.9% of patients. Diabetes and hypercholesterolemia were found in 40% of the study population, and a history of hypertension was present in 43.3% of patients. A history of smoking was present in 34% of the study patients. Almost three-fourth (72.7%) of the patients who underwent coronary angiogram were between the ages of 50 and 69 (n = 453/623) years. Obstructive CAD was found in 75.3% (n = 469/623) of patients. The baseline characteristics are summarized in Table 1.
Central pressures and risk factors
The pressure indices showed a steady increase as age advanced and females had higher values of pulsatility (0.74 vs. 0.63; P ≤ 0.001) and pulsatility index (1.02 vs. 0.84; P ≤ 0.001) when compared to males. The mean values of pulsatility were found to be significant in those with hypertension (P = 0.020) and in females (P ≤ 0.001). Comparing those with and without risk factors across the various Gensini tertiles by ANOVA test, patients with risk factors had significant differences in the pulsatility (P = 0.009) and pulsatility index (P = 0.004).
Central pressures and coronary artery disease
The mean values of the central aortic pressure indices are summarized in [Table 2]. The three tertiles of Gensini score were <21, 21–68, and >68. Across the three Gensini tertiles, PP, pulsatility, and pulsatility index showed an increase in the first two tertiles and there was a paradoxical decrease in the values in the third tertile [Supplementary Table 1]. The mean pressures did not show any consistent trend. Comparison of the various Gensini tertiles using ANOVA test showed significance in the pulsatility (P = 0.003) and pulsatility index (P = 0.001). Post hoc comparison between the different Gensini tertiles with pulsatility and pulsatility index as dependent variables showed significance in all groups, except across the 1st and 3rd tertile. However, no definite correlation could be obtained between the aortic pulsatility and Gensini score. Comparing the obstructive CAD versus nonobstructive CAD, there was no significant difference in the various pressure indices between the two groups.
Regression analysis with age, sex, smoking status, type 2 DM, hypertension, hypercholesterolemia, medication use, and Gensini score as confounders showed age, sex, and smoking status to be important predictors of pulsatility [Table 3].
Central and peripheral pressures
Comparing the central and peripheral pressures, a good correlation was obtained between the central and peripheral PP (correlation coefficient r = 0.833) and mean pressures (r = 0.652) [Figure 1] and [Figure 2].
|Figure 1: The central and peripheral pulse pressures showed good correlation with a correlation coefficient of r = 0.833|
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|Figure 2: The central and peripheral mean pressures showed a fairly good correlation with a correlation coefficient of r = 0.652|
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Central pressures and cardiovascular outcomes
At the end of 6 months, complete follow-up could be obtained of only 428 patients (68.7%) with outcomes in 48 patients (11.2%): ACS (n = 36); death (n = 11), and stroke (n = 1). No patient had more than one outcome. Evaluating the composite outcome, it was found to be more in males and in the 2nd and 3rd Gensini tertiles. The central PP, pulsatility, and pulsatility index were found to be higher in those who had ACS as outcome [Table 4]. However, analysis of additional PP indices – PP amplification, absolute PP amplification, and relative PP amplification – though showed a rise in the number of events failed to prove a definite association with cardiovascular outcomes.
| Discussion|| |
Central aortic BP indices are emerging risk factors in the pathogenesis of CVD.,,,,,,, The primary objective of our study was to ascertain whether the central aortic pressure indices have any association with the severity of CAD.
In our study, the measures of the pulsatile component of central aortic pressures such as PP, pulsatility, and pulsatility index showed worsening values as the severity of CAD increased from the 1st Gensini tertile to the 2nd Gensini tertile. However, the mean pressures which represented the steady-state component of BP did not show any definite relation with worsening severity of CAD. A decrease in the value of the indices, especially pulsatility and pulsatility index, was seen in the third Gensini tertile which was not expected. But then, most of our patients were in the age group of 50–69 years and the vast majority of patients in the third tertile were between the ages of 50 and 69 years. In this age group, the measures of central pulsatility and PP become less reliable, as various other factors such as aortic stiffness come into play. This could be the most plausible explanation for the decrease in the central aortic pressure indices in the third tertile. However, when the obstructive and nonobstructive CAD groups were compared, the group with obstructive CAD showed worsening PP and pulsatility which was in accordance with previous studies,, though a significant difference could not be proven between the two groups (P = 0.075 for pulsatility and P = 0.096 for pulsatility index).
Of the various central pressure indices, only the central pulsatility was found to be significantly influenced by the various clinical and demographic variables. The higher pulsatility in the females would be explained by their higher mean age (57 years), postmenopausal state, and lower numbers in the study. The most important variables affecting the pulsatility were age, smoking status, and hypertension which was demonstrated to be significant both in univariate and multivariate analyses. Coming to the effect of drugs on the central pressures, we could not find a significant difference between the various groups of medications as most of the patients were on multiple medications and the definite effect of a particular drug class could not be predicted even in the multivariate analysis. However, the CAFÉ study had demonstrated the differential effect of the various BP-lowering drugs on central aortic pressures and clinical outcomes.
Coming to the next important question, whether the central BP indices influenced the cardiovascular outcomes., In our study, those who had ACS (n = 36) had worsening central aortic pressure indices (P = 0.001 for PP, P = 0.004 for pulsatility, and P = 0.005 for pulsatility index), though no such significance was noted in the mortality (n = 11) group, with lower number of events being the possible reason for nonattainment of significance. Additional indices of PP such as PP amplification, absolute PP amplification, and relative PP amplification showed a trend toward increase in the number of cardiovascular events in the higher tertiles, but statistical significance was not attained. A study on pulse pressure amplification in elderly subjects showed that lower PP amplification was associated with better outcomes. Short follow-up time was an important factor which could have influenced the results. However, in those with outcomes, the mean values of the pressure indices were found to be worse than the study population mean, providing corroborative evidence of its role in the prediction of adverse cardiovascular events in the future. Finally, is there any relation between the central and peripheral pressures? Our study clearly showed that the central and peripheral mean pressures and PP had good correlation, and this was in accordance with a previous study though some studies have failed to show similar results.
The most important limitation of the study was the short follow-up time of 6 months. Only a longer follow-up could definitely predict the role of central BP indices in the prediction of future adverse cardiovascular events. A higher sample size would have increased the accuracy of the results and would have been more representative of the general population.
| Conclusions|| |
In fact, there is a real paucity of data on central aortic pressure indices representing the Indian population where the incidence of diabetes and CAD is significantly high. A definite association between the central aortic pressure indices and severity of CAD could not be proven though there was a trend across the first two Gensini tertiles. Central pulsatility shows increased values in those with established cardiovascular risk factors, with age, BP, and smoking status being the important determinants of central pulsatility. Central and peripheral PP and mean pressures have shown to have good correlation. The pulsatile component of the central pressures may predict future cardiovascular events. However, only larger studies with longer follow-up will confirm the relation.
What is already known?
Central aortic pressure is coming up as a very important prognostic risk marker in the evaluation of CVD. Several studies have shown mixed results, and the exact place of central aortic pressures is still undecided.
What this study adds?
The study clearly shows that the pulsatile component of the central aortic BP is significantly associated with proven cardiac risk factors and a positive trend toward severity of CAD. In fact, it may emerge in the near future as the next surrogate in the prediction of future cardiovascular events. The study however needs further validation from other studies involving similar population to arrive at a conclusion. Central aortic blood pressure: Is this the next surrogate in cardiology?
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]