New noninvasive vascular tests could improve the prediction and early diagnosis and treatment of cardiovascular diseases

Coronary heart disease (CHD), cardiovascular disease (CVD), hypertension, and heart failure (HF) are major disease states accounting for high disability and death with significant socioeconomic consequences.1, 2 Therefore, identifying the risk factors responsible for their occurrence could facilitate their early prediction, diagnosis, and treatment. So far, the Framingham Risk Score (FRS) has been used for their prediction and treatment, but its predictive value has been limited. The FRS was first introduced by Wilson et al,3 from the Framingham studies research group in 1998, and included the integration of systolic blood pressure (SBP), age, sex, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and, in addition, smoking, diabetes, and hypertension. The integration of these risk factors proved to be useful for the 10- to 20-year prediction of future incidence of CHD. Later, an increased inter-arm SBP difference (IASBPd) of ≥10 mm Hg was added by the same group since it is considered an important cardiovascular (CV) risk factor.4 Recently, new noninvasive vascular tests incorporating the simultaneous measurement of IASBPd and the inter-leg SBP difference (ILSBPd) have been developed and when added to the FRS could further increase its predictive value. In this issue of the journal, Yu et al5 report on the predictive value of measuring the simultaneous IASBPd and ILSBPd in combination with the measurement of the ankle-brachial index (ABI), by using an automated device (Collin VP-1000). This devise illustrated in Figure 1 is automated, can measure simultaneously the SBP in all 4 extremities by an oscillometric method, also calculate the ABI in addition to other tests, such as the pulse wave velocity (PWV), the pulse rate (PR), and the arterial waveforms by a technician within 5-10 min, and provide a written report.6 In addition, by using cardiac ultrasonography they measured the left ventricular internal diameter in diastole (LVIDd), septal wall thickness in diastole (SWTd), and the posterior wall thickness in diastole (PWTd) and calculated the left ventricular mass in grams (LVMg) in 2621 elderly patients from the Northern Shanghai Study, mean age 70 years. Most of their patients were hypertensive and had several cardiovascular risk factors. The test results showed that 635 (24.2%) patients had IASBPd ≥10 mm Hg, 482 (18.4%) patients had IASBPd ≥15 mm Hg, and 354 (13.5%) patients had an ABI ≤0.9. They found that the prevalence of organ damage progressed from the group with the lowest to the group with the highest test values. Patients with abnormal IASBPd and ILSBPd had higher prevalence of cardiovascular risk factors, such as carotid plaque, arterial stiffness, and left ventricular hypertrophy (LVH) than those with abnormal only one ILlimbSBPd. Scientific society guidelines for the diagnosis and treatment of hypertension recommend the measurement of BP in both arms at the initial evaluation of patients, because it could detect significant differences in BP between the arms and signify the presence of abnormalities from either congenital or acquired conditions such as atherosclerosis of the subclavian or brachial artery in older patients that can be corrected early.6, 7 Significant difference in SBP >15 mm Hg in IASBPd has been associated with increased incidence of CVD.6, 7 In the past, doing this by hand was time consuming and most physicians did not perform these test. Presently, there is a device available (Figure 1) that can do these measurements more accurately and simultaneously by a technician within 5 minutes.8 In their study, Yu et al5 found that patients with higher ILimbSBPd values had a greater burden of CV risk factors, such as atherosclerosis (carotid plaque), arterial stiffness, and LVH than patients with lower or normal ILimbSBPd values. Taken all together, this study demonstrates that the combination of ILimbSBPd may be a better marker of generalized atherosclerosis than each individual IASBPd, ILSBPd, or ABI. Although this is not an outcomes study, their findings could predict future CV events as has been demonstrated by other investigators.9, 10 In a recent study of 3133 elderly, community-dwelling Chinese patients mean age 69 years, Sheng et al,9 using all four extremities, found that patients with abnormal values of ILimbSBPd were at a increased risk for all-cause and CV mortality. After 4 years of follow-up, they found that patients with abnormal IASBPd and ILSBPd had higher all-cause mortality and CV mortality (P ≤ 0.01 and P ≤ 0.04, respectively). Similarly, Clark et al,10 in a review and meta-analysis of 20 studies, found that IASBPd of 15 mm Hg or greater was associated with significant subclavian artery stenosis with peripheral vascular disease, HR 2.5 (95% CI 1.6-3.8), and preexisting cerebrovascular disease, HR 1.7 (95% CI 2.0-26.0), and had increased CV mortality, HR 1.7 (95% CI 1.1-2.5), and all-cause mortality, HR 1.6 (95% CI 1.1-2.3). The authors state that patients with IASBPd of 10 mm Hg or greater, or 15 mm Hg or greater, need further vascular assessment to identify abnormal CV risk factors. Importantly, an IASBPd of 15 mm Hg or greater could be an indicator of risk of vascular disease and death. The Japanese investigators have been very progressive in this regard by developing these new noninvasive vascular tests with the hope to increase their predictive value alone or in combination with the FRS. They have added several other noninvasive vascular tests, such as Reactive Hyperemia-Peripheral Tonometry (RH-PAT) and the Cardio-Ankle Vascular Index (CAVI) in addition to the existing noninvasive vascular tests, such as the ABI, PWV, augmentation index (Aix), pulse pressure (PP), and central pulse pressure (CPP). The RH-PAT is similar to flow-mediated dilation (FMD), but in addition, it measures peripheral microvascular endothelial function and nitrogen oxide (NO) release by calculating the reactive hyperemia index (RHI), which could reflect the availability of NO and the adverse effects of obesity, diabetes, and smoking on RHI.11, 12 Low values of RHI have been associated with endothelial dysfunction and prognosticate the future incidence of CHD and coronary plaque formation.13 In addition, low values of RHI could indicate, besides generalized atherosclerosis, the presence of vasospastic angina pectoris in women with a predictive value of specificity and sensitivity of 80%.14 Other studies have also confirmed the prognostic value of RHI for a variety of cardiovascular conditions such as CV adverse events, coronary artery disease (CAD), and HF with preserved ejection fraction.15-17 The CAVI was developed to study the extent of arteriosclerosis throughout the aorta, femoral artery, and tibial artery, and it is measured automatically with the device illustrated in Figure 1. The PWV is measured from the aorta to the ankle, and the CAVI is calculated automatically through an internal formula.18 The value of CAVI increases with age and is higher in men than women.8, 19 Also, several studies have shown that it has a good predictive value with future incidence of CV events.20-22 The exception is perhaps a recent review and meta-analysis of nine prospective studies (n = 5214 patients) and 17 cross-sectional (n = 7309 patients) with high CV risk, that showed a modest association of CAVI with incident CVD, highlighting the need for future more organized, long-term outcome studies.23 To test the predictive value of CAVI, a new long-term (5 year) study (Evaluating the Cardio-Ankle Vascular Index to Predict Cardiovascular Events in Japan: A Prospective Multicenter Study-CAVI-J) will evaluate the predictive value of CAVI on CV events in 3000 Japanese patients ages 40-74 years with at least one CV risk factor at baseline.24 Hopefully, this study when completed will provide the necessary information regarding the value of these noninvasive vascular tests to predict future CV events and whether their addition to FRS will further increase its predictive value. Regardless, more future long-term, randomized, controlled outcomes studies will be necessary to establish the validity of these new noninvasive vascular tests for the future prediction of CVD and death. The author declares no conflict of interest and that no funds were received for the preparation of this manuscript.