Do Different Arterial Stiffness Parameters Provide Similar Information in High-Risk Patients for Coronary Artery Disease?

Arterial stiffness is a recognized factor associated with an increased risk of coronary artery disease (CAD) and is currently used as a predictive factor, especially as an index predictive of target organ damage in hypertension.1-3) According to the Framingham Heart Study, systolic blood pressure (SBP) is positively associated with coronary heart disease, whereas diastolic blood pressure (DBP) has a negative relationship. As a result, pulse pressure widening was found to be the most significant risk factor of coronary disease and mortality.4) It is already recognized that arterial stiffness, the main mechanism underlying pulse pressure widening, is an independent risk factor for cardiovascular disease and stroke.5), 6)

Numerous methods have been developed to assess arterial stiffness, including pulse wave velocity (PWV) and augmentation index (AI). PWV is a widely used, non-invasive method for evaluating arterial stiffness and atherosclerosis. Increased PWV is a marker of atherosclerosis and has been shown to reliably predict the presence and extent of atherosclerotic vascular disease.7), 8)

The AI reflects arterial stiffness by pulse wave analysis and is a hemodynamic index representing arterial stiffness. AI is known to increase at the early phase of atherosclerosis, making it a candidate screening tool for assessing the risk of cardiovascular disease. Numerous studies have focused on this potential. Although some studies have suggested that the AI is associated with cardiovascular risk factors that correlate with cardiovascular disease, others have demonstrated no such relationship. According to Hope et al.,9) the AI is not associated with the extent of coronary disease, nor its severity. Therefore, the association between AI and cardiovascular disease has not been firmly established and remains a topic of great debate.4), 9-11) Despite several studies on the relationship between PWV or AI and the prevalence of coronary heart disease, relatively few studies have simultaneously compared the correlation between these coronary artery indices and the status of coronary arteries as assessed by coronary angiography. Therefore, this study concurrently investigated the association between PWV and peripheral augmentation index (pAI) and CAD.

We analyzed medical records from our coronary laboratory for data on CAD, and from our non-invasive laboratory for data on PWV and pAI. Patients who visited Wonju Severance Christian Hospital from May 2010 to March 2012 were enrolled. A total of 7020 and 6373 patients underwent coronary angiography and PWV measurement, respectively. Among them, 1030 patients underwent both tests, and after excluding patients with missing data, the final analysis included 965 patients (Fig. 1).

Fig. 1
Study flow chart. ABI: ankle brachial index.

• Click for larger image

Recently, numerous researchers have taken an interest in arterial stiffness, and a number of related studies have been performed. These studies have found that increased arterial stiffness is a useful predictive factor that is associated with clinical events, not only in a hypertensive patient group but also in populations with type 2 diabetes or end-stage renal disease, and in the geriatric and general population.7), 12-15) Our study is unique in that it simultaneously compared PWV and peripheral augmentation with different manifestations of CAD in a large population.

Pulse wave velocity is a well-known independent predictive factor of cardiovascular disease;1) however, few studies have investigated the difference in PWV according to the extent of coronary vessel disease. We found that baPWV increased according to the severity of CAD (none/minimal, 1-vessel, 2-vessel, or 3-vessel disease) (Table 2). This suggests that baPWV not only contributes to the presence of CAD, but also to the progression of cardiovascular disease. A similar result was observed in a study performed by Mattace-Raso et al.,1) although the sample size of their study was small (40 patients). Our study included 965 patients and our data may therefore be more meaningful.

In univariate analysis, baPWV was found to be a potentially useful independent predictive factor, similar to age, male sex, hypertension, diabetes, dysplipidemia, and smoking (Table 5).

On the other hand, pAI was significantly lower in patients with CAD (Table 1). This is contrary to the results of previous studies, which demonstrated elevated AI in early atherosclerosis and suggested an association between the pAI and CAD. There are several possible explanations for the decreased pAI in our patients with CAD.

First, the antihypertensive drug used in these patients could be a confounding factor. In our study, patients with CAD were found to have lower SBP than those without CAD because of the greater use of antihypertensive medication. Because pAI is positively correlated with SBP,16) this finding suggests that antihypertensive treatment could affect the pAI by lowering the blood pressure.

Second, as mentioned above, the patients in this study were older than the general population. Mattace-Raso et al.1) reported that the pAI increases with age until about 55 years, and slowly decreases down to a plateau thereafter. In our study, the mean age of the enrolled patients was 63.7±11.6 years. It is known that cardiovascular risk is greater among elderly men, and the decrease in pAI in our patients with CAD may be explained by this finding.

Third, pAI was significantly greater in females than in males. pAI tends to be overestimated among females because of their shorter height, arms, and legs. Since male sex is a major risk factor of CAD, the ratio of females was higher in the non-CAD group (49.4% vs. 34.0%), and this may have led to a higher average pAI value.

Lastly, pAI is a parameter derived from the reflected wave through pulse wave analysis, rather than a directly measured value. Therefore, the results might be influenced by the equipment, the measurement, and the patient. Furthermore, the current measurement method has not been validated, which may have resulted in measurement bias.

This study has several limitations. First, baPWV reflects arterial stiffness, which is influenced by various factors, including age, gender, and hypertension.17) In addition to applying large mechanical stress to the vascular wall as a result of high intravascular pressure, hypertension leads to growth of vascular smooth muscle that is associated with elevated levels of catecholamine, angiotensin II, and other cytokines, causing proliferation of fibrous protein within the tunica intima and loss of elasticity, both of which contribute to an increase in arterial stiffness.17), 18) Because both age and hypertension contribute more strongly to coronary heart disease than baPWV, the influence of baPWV on CAD may have been reduced after adjusting for these factors.

Second, the study group consisted of high-risk patients. This study was performed on symptomatic patients who underwent coronary angiography, not on the general population. The median PWV for this group was 16.2±3.5 m/sec, which is higher than that reported by Han et al.8) in a study performed in a Korean population (11.23±5.10 m/sec), and the subjects' mean age was also higher (63.7±11.6 years).

In conclusion, increased baPWV and decreased pAI were associated with the presence of CAD in the elderly. pAI may be decreased in elderly and male patients with cardiovascular disease and may be attributable to the aforementioned confounding factors, such as age and history of anti-hypertensive medications, rather than an actual decrease in arterial stiffness. Therefore, considerations of these confounding factors must always be made when utilizing pAI in clinical practice. In addition, this study targeted high-risk patients, and a large-scale epidemiologic study involving the general population is necessary.