Abstract
Background
Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess cardiovascular disease (CVD) risk in eastern Asia. We examined whether baPWV is associated with coronary atherosclerosis in an international study of healthy middle-aged men.
Methods
A population-based sample of 1,131 men aged 40–49 years was recruited– 257 Whites and 75 Blacks in Pittsburgh, US, 228 Japanese-Americans in Honolulu, US, 292 Japanese in Otsu, Japan, and 279 Koreans in Ansan, Korea. baPWV was measured with an automated waveform analyzer (VP2000, Omron) and atherosclerosis was examined as coronary artery calcification (CAC) by computed-tomography (GE-Imatron EBT scanner). Association of the presence of CAC (defined as ≥10 Agatston unit) was examined with continuous measure as well as with increasing quartiles of baPWV.
Results
As compared to the lowest quartile of baPWV, the multivariable-adjusted odds ratio (95% confidence-interval [CI]) for presence of CAC in the combined sample was 1.70 (0.98, 2.94) for 2nd quartile, 1.88 (1.08, 3.28) for 3rd quartile, and 2.16 (1.19, 3.94) for 4th quartile (p-trend = 0.01). The odds for CAC increased by 19% per 100 cm/s increase (p<0.01), or by 36% per standard-deviation increase (p<0.01) in baPWV. Similar effect-sizes were observed in individual races, and were significant among Whites, Blacks and Koreans.
Conclusion
baPWV is cross-sectionally associated with CAC among healthy middle-aged men. The association was significant in Whites and Blacks in the US, and among Koreans. Longitudinal studies are needed to determine its CVD predictive ability.
Keywords: Vascular stiffness, atherosclerosis, vascular calcification, pulse wave analysis, arteriosclerosis
1.0 Introduction
Coronary heart disease (CHD) remains the leading cause of mortality in the United States (US) in spite of a significant decline in age-adjusted CHD over the past 5 decades.1 The burden of CHD is expected to increase by 16% over the next 20 years due to an aging population and increased survival after suffering from a coronary event.2 One of the current strategies for further reducing CHD is to implement prevention strategies among individuals who are at an intermediate CHD risk and who would benefit most from CHD prevention therapy.3
Coronary artery calcification (CAC), assessed by computed-tomography scan (CT), is a strong independent predictor of future CHD events among asymptomatic individuals. Use of CAC imaging is currently recommended among individuals who are at low to intermediate risk i.e.10-year risk of cardiovascular disease (CVD) risk between 6%–20%.4 However, CAC imaging exposes an individual to ionizing radiation, which may limit its wider applicability as a screening tool. Also, the cost-effectiveness of routine CT imaging among asymptomatic individuals is not yet established.5
Brachial-ankle pulse wave velocity (baPWV) is a highly reproducible measure of arterial stiffness that has shown promise as a predictor of future CVD among east Asian populations.6 Unlike carotid-femoral pulse wave velocity (cfPWV), which is a measure of central arterial stiffness, baPWV is a combined measure of central and peripheral arterial stiffness.7 Although cfPWV is considered a gold standard marker for central arterial stiffness and a predictor of future CHD, it has not gained acceptance into clinical practice esp. in the West8 – possibly due to requisite operator training and expertise, and also patient’s discomfort with groin exposure. In contrast, baPWV is currently used routinely in Japan and South Korea to assess CVD risk.9 baPWV requires application of cuffs on the four extremities, is convenient to measure in a clinic, requires little technical expertise, and, unlike cfPWV, does not require exposure to the inguinal region. We have previously reported a significant association between baPWV and the presence of CAC among obese post-menopausal women in the US.10 However, the utility of baPWV in the US remains to be thoroughly examined.11,12
We, therefore, examined the association between baPWV and presence of CAC in the Electron-beam computed tomography and Risk factor Assessment among Japanese and U.S. Men in the Post-World War II birth cohort (ERA JUMP Study), an international study of subclinical atherosclerosis among 40–49 year old men. We hypothesized that baPWV is significantly associated with presence of CAC in this healthy sample of middle-aged men.
2.0 Methods and Materials
2.1 Participants
During 2002–2006, a population-based sample of 1,335 men aged 40–49 years, with no clinical CVD or other severe diseases, was obtained from 4 centers: 310 Whites and 107 Blacks from Pittsburgh, Pennsylvania, US; 303 Japanese Americans from Honolulu, Hawaii, US; 313 Japanese from Kusatsu city, Shiga, Japan; and 302 Koreans from Ansan, Gyeonggi-do, South Korea as previously described.13 Written informed consent was obtained from all participants. The study was approved by the Institutional Review Boards of the following institutions: the University of Pittsburgh, Pittsburgh, Pennsylvania, US; the Kuakini Medical Center, Honolulu, Hawaii, US; Shiga University of Medical Science, Otsu, Japan; and Korea University, Seoul, South Korea.
2.2 Pulse Wave Velocity Assessment
At the start of the study, staff from the University of Pittsburgh’s Ultrasound Research Laboratory visited the Honolulu site to train the sonographers in Honolulu and from South Korea for PWV measurements. In addition, continuous quality control measures were implemented for all the sites, including Japan. PWV measurements were automatically generated using a noninvasive and automated waveform analyzer (VP2000, Omron, Japan). This device provides automated measures of baPWV on both right and left sides – average of the two sides was used for our study. Following 10 min of rest in a supine position, occlusion and monitoring cuffs were placed around both arms and both ankles of the participant. The arm cuffs were placed on the skin or over light clothing, and the ankle cuffs were directly placed over the skin. ECG electrodes were placed on both wrists and a phonocardiogram i.e. a microphone for detecting heart sounds was placed on the left edge of the sternum. The path length for baPWV was calculated using height-based formulae.14 PWV was calculated as the distance between arterial sites divided by the time between the feet of the respective waveforms. Intra-class correlations (ICC) for re-examination of baPWV was 0.97 within technician, and 0.91 between technicians.15
2.3 Coronary Artery Calcification
CAC scanning was performed with a GE-Imatron C150 EBT scanner (GE Medical Systems, South San Francisco, California) at all centers as published earlier in detail.16 Briefly, a standardized protocol was used to perform CAC scanning; 30–40 contiguous, 3-mm-thick transverse images from the level of the aortic root to the apex of the heart were obtained during maximal breath holding by using electrocardiogram triggering (60 percent of the R-R interval) so that each 100 millisecond exposure was obtained during the same phase of the cardiac cycle.16 One trained reader at the University of Pittsburgh read the images using a DICOM (Digital Imaging and Communications in Medicine) workstation and software by AccuImage (AccuImage Diagnostic Corporation, San Francisco, California). The software program implements the widely accepted Agatston scoring method.17 The reader was blinded to the participant’s characteristics and the study centers. ICC for re-examination of electron-beam computed tomography scans was 0.98. Presence of CAC was defined as ≥ 10 Agatston Unit (AU) as a score between 0–10 is likely to be noise;16 a cut-off value of 10 AU maximizes the positive predictive value of CAC for underlying plaque disease by minimizing any contribution from beam hardening or motion artifact.
2.4 Risk Factor Assessment
All participants underwent a physical examination, completed a lifestyle questionnaire, and a laboratory assessment as described previously.13,18,19 Body weight and height were measured while the participant was wearing light clothing without shoes. Body-mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters. Blood pressure and heart rate were measured after the participant emptied his bladder and sat quietly for 5 minutes. Blood pressure was measured twice on right arm with an automated sphygmomanometer (BP-8800, Colin Medical Technology, Komaki, Japan) using an appropriate sized cuff; average of the two measurements was used. Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg or use of anti-hypertensive medications.20 Mean blood pressure (MBP) was calculated as: [DBP + 1/3*(SBP-DBP)]. Venipuncture was performed early in the clinic visit after a 12-hour fast. Blood samples were stored at −80°C and shipped on dry ice from all centers to the University of Pittsburgh. Serum lipids were determined using the protocol standardized by the Centers for Disease Control and Prevention.21 Serum glucose was determined by using hexokinase–glucose-6-phosphate-dehydrogenase enzymatic assay. Diabetes was defined as individuals with fasting glucose ≥7.0 mmol/l or use of medications for diabetes.22 Alcohol drinking was defined as drinking two or more times per week. Smoking was measured as history of ever smoking. Use of blood pressure-lowering, diabetes, and lipid-lowering medications were ascertained through questionnaire. Data collection procedures were standardized across all centers.
We excluded participants taking antihypertensive medications (n=140), those with extreme outliers i.e. CAC >1,000 AU (n=3), and those with extremely high baPWV i.e. baPWV >2,000 cm/s (n=4). The final sample for this study consisted of 1,131 men (257 Whites, 75 Blacks, 228 Japanese Americans, 292 Japanese in Japan, and 279 Koreans) with complete data.
2.5 Statistical Methods
Descriptive characteristics of the sample population were examined, including demographics, CVD risk factors, baPWV, and CAC. Comparisons of population characteristics were made using t-tests for continuous variables, and chi-square tests for categorical variables. Non-parametric tests were used for skewed variables. Logistic regression was used to examine the association between baPWV(per 100 cm/s increase, per 1 SD increase) and presence of CAC (≥ 10 AU) – in an unadjusted model (crude model), in an age-, race-adjusted model (model I), as well as in multivariable models adjusted for CVD risk factors including race, age, SBP, LDL-c, ever smoking, and diabetes (model II), and further adjusting for HDL-c, BMI and alcohol drinking (model III). As the distribution of the CAC scores was skewed with a large majority of the participants having zero CAC score, tobit regression (PROC QLIM) with left-censored data was performed to examine the association of CAC with baPWV23 – for this analysis, log-transformation was performed for non-zero CAC scores. Unadjusted analysis was also performed after stratification by race-ethnicity. Further, we categorized the baPWV into quartiles and examined their association with the presence of CAC keeping lowest quartile of baPWV as the reference category. Similar to the previous analysis, the association was examined using unadjusted model, race-adjusted, and multivariable-adjusted models in logistic regression; further unadjusted analyses was performed after stratification by race. All data analysis was performed using SAS/STAT software, version 9.3 of the SAS System, Cary, NC, USA.
3.0 Results
Participants with CAC (n=191) were slightly older (46.1 vs. 44.9 years, p<0.001), had higher BMI (27.0 vs. 25.4 kg/m2, p<0.001), SBP (126.3 vs. 122.7 mmHg, p<0.001), LDL-c (3.5 vs. 3.3 mmol/l, p<0.001), and triglycerides (1.7 vs. 1.5 mmol/l, p<0.01) than those with no CAC (n=940). Prevalence of diabetes was non-significantly higher among those with CAC (8.4% vs. 5.6%, p=ns). Further, baPWV was significantly higher among those with CAC (1392.6 vs. 1317.0 cm/s among those with no CAC, p<0.001). (Table 1) The mean (SD) of baPWV (cm/s) among individual races was: Whites 1312.9 (150.8), Blacks 1370.0 (161.0), Japanese Americans 1415.3 (160.8), Japanese in Japan 1298.0 (174.8), and Koreans 1297.8 (137.2).
Table 1.
Presence of cardiovascular risk factors among 40–49 year old men in the ERA JUMP Study, by presence of CAC (≥10 AU).
| Population characteristic | CAC (n=191) | No CAC (n=940) | p-value |
|---|---|---|---|
| Age (years) | 46.1 (2.6) | 44.9 (2.9) | <0.001 |
| BMI (kg/m2) | 27.0 (3.9) | 25.4 (3.7) | <0.001 |
| Systolic Blood Pressure (mmHg) | 126.3 (12.9) | 122.7 (13.3) | <0.001 |
| Mean blood pressure (mmHg) | 93.8 (9.9) | 90.6 (10.9) | <0.001 |
| Heart rate (per minute) | 66.8 (9.5) | 65.3 (0.0) | 0.047 |
| Hypertension (%)$ | 17.3 | 13.8 | ns |
| Glucose (mmol/l) | 5.8 (0.7) | 5.8 (1.0) | ns |
| Diabetes (%)‡ | 8.4 | 5.6 | ns |
| Pack-years of smoking†, (years) | 1.2 (0, 22) | 2.5 (0, 19) | ns |
| Ever Smoking (%) | 55.0 | 55.5 | ns |
| Ethanol intake (g/day)† | 8.2 (0.4, 28.8) | 7.5 (0.1, 24.7) | ns |
| Alcohol drinker (%) | 49.7 | 47.3 | ns |
| LDL-cholesterol (mmol/l) | 3.5 (0.9) | 3.3 (0.9) | <0.001 |
| HDL-cholesterol (mmol/l) | 1.3 (0.3) | 1.3 (0.3) | ns |
| Triglycerides, (mmol/l†) | 1.7 (1.1, 2.3) | 1.5 (1.0, 2.1) | 0.04 |
| baPWV (cm/s) | 1392.6 (162.3) | 1317.0 (160.8) | <0.001 |
| CAC Score† | 45.5 (20.8, 99.9) | NA | |
| CAC Score ≥ 100 AU (%) | 24.6 | NA |
Values are mean ± SD unless otherwise mentioned.
Hypertension was defined as presence of one or more of following – i) Systolic blood pressure (BP) ≥140 mmHg, ii) Diastolic BP ≥90 mmHg, or iii) use of antihypertensive medication
Diabetes was defined as either glucose ≥7 mmol/l or use of diabetic medication, or both
Median (IQR)
ns = not significant
CAC = Coronary Artery Calcification, AU = Agatston unit, LDL = low-density lipoprotein cholesterol, HDL = high-density lipoprotein cholesterol, baPWV = brachial-ankle pulse wave velocity, BMI = body-mass index, IQR = inter-quartile range
There was a trend for higher prevalence of CAC with higher baPWV. (Figure 1) With every 100 cm/s increase in baPWV, the odds for presence of CAC increased by 31% (p<0.001) in the crude model, 24% (p<0.001) after adjustment for age and race (model I), and 19% (p<0.01) in multivariable-adjusted models (model II and model III). Similarly, with every 1 SD increase in baPWV, the odds for CAC increased by 61% (p<0.001), 46% (p<0.001), and 36% (p<0.01) in crude, age-race adjusted and multivariable adjusted models respectively. (Table 2) When examining baPWV by quartiles, we found a significant trend for increasing prevalence of CAC with increasing baPWV quartiles in unadjusted and age-race adjusted models, as well as after multivariable-adjustment. (Figure 2) In a multivariable-adjusted tobit regression model, baPWV was significantly associated with higher CAC (p=0.002). In a supplementary analyses where we adjusted for MBP instead of SBP in the regression models, the results remained materially the same.
Figure 1. Prevalence of CAC (10 - 99 AU and ≥100 AU) with baPWV.
CAC = coronary artery calcification, AU = Agatston unit, baPWV = brachial-ankle pulse wave velocity
Table 2.
Association between baPWV and CAC: odds ratio (95% confidence interval) for presence of CAC (≥ 10 AU) using continuous variables of baPWV (N=1,131)
| baPWV (per 100 cm/s) | baPWV (per SD change) | P-value | |
|---|---|---|---|
| Crude | 1.31 (1.20, 1.44) | 1.61 (1.37, 1.90) | p<0.001 |
| Model I | 1.24 (1.12, 1.37) | 1.46 (1.22, 1.74) | p<0.001 |
| Model II | 1.19 (1.06, 1.34) | 1.36 (1.10, 1.67) | p=0.004 |
| Model III | 1.19 (1.05, 1.34) | 1.36 (1.10, 1.68) | p=0.005 |
| Race-Specific Analysis** | |||
| Caucasian (n=281) | 1.30 (1.07, 1.58) | 1.49 (1.11, 2.01) | p=0.009 |
| African American (n=83) | 1.83 (1.22, 2.73) | 3.03 (1.45, 6.33) | p=0.003 |
| Japanese American (n=235) | 1.17 (0.98, 1.40) | 1.32 (0.97, 1.81) | p=0.078 |
| Japanese in Japan (n=292) | 1.15 (0.94, 1.41) | 1.31 (0.88, 1.93) | p=0.183 |
| Korean (n=280) | 1.36 (1.03, 1.79) | 1.55 (1.04, 2.31) | p=0.030 |
Model I: Age, Race-adjusted.
Model II: Model I + systolic blood pressure, low density lipoprotein-cholesterol, ever smoking, alcohol drinking, and diabetes
Model III: Model II + high density lipoprotein cholesterol, body-mass index and heart rate
CAC = coronary artery calcification, baPWV = brachial-ankle pulse wave velocity, AU = Agatston unit, SD = standard deviation
Race-specific analysis was unadjusted for confounders
Figure 2. Association between baPWV and CAC: odds ratios for presence of CAC (≥10 AU) with increasing quartiles of baPWV (n=1,131).
Model I: Age, Race-adjusted.
Model II: Model I + systolic blood pressure, low-density lipoprotein cholesterol, ever smoking and diabetes
Model III: Model II + high-density lipoprotein cholesterol, alcohol drinking, heart rate and body-mass index
CAC = coronary artery calcification, AU = Agatston unit, baPWV = brachial-ankle pulse wave velocity
Among individual race-ethnicities, the prevalence of CAC was: Whites (24.9%), Blacks (15.7%), Japanese Americans (28.1%), Japanese in Japan (10.3%), and Koreans (10.0%). There was no significant interaction between race and baPWV in the model for the presence of CAC (p=0.28). When analysis was performed after stratifying by race, in unadjusted model, the association between baPWV and CAC prevalence was significant among Whites (OR: 1.30 per 100 cm/s increase; p<0.01), Blacks (OR: 1.83 per 100 cm/s increase, p<0.01), and Koreans (OR: 1.36 per 100 cm/s increase; p=0.03); the association was not significant among Japanese Americans and Japanese in Japan although the odds for presence of CAC were higher with higher baPWV. (Table 2) When examining baPWV by quartiles in individual races, the analysis could not be performed among Blacks due to sample size limitations. Among other races, the p-trend for higher presence of CAC with higher quartiles of baPWV was significant among Whites in unadjusted models. (Supplementary table 1)
4.0 Discussion
We found that baPWV was significantly associated with CAC among healthy middle-aged men without CVD. This association was independent of traditional CVD risk factors. When stratified by race, the association was significant among Whites, Blacks, and Koreans. This is the first international study to examine the association between baPWV and coronary atherosclerosis among healthy middle-aged men.
Previous studies have reported a similar association of baPWV with CAC among 504 obese postmenopausal women in the US,10 and among 654 patients without CVD in Taiwan.24 We have previously shown that among 504 obese postmenopausal women, the multivariable-adjusted odds ratio for presence of any CAC were 1.94 (95% CI 1.01, 3.70), 2.90 (95% CI 1.50, 5.58), and 2.21 (95% CI 1.11, 4.42) for quartiles 2, 3, and 4 respectively as compared to the lowest quartile of baPWV; the association was stronger for baPWV than for cfPWV.10 Similarly, in the Taiwanese study, the mean (±SD) CAC score was higher (35.7 ± 173.6, 100.2 ± 249.7, and 227.6 ± 412.5, p-trend<0.001) with higher baPWV (<1400 cm/s, 1400 cm/s-1800 cm/s, and >1800 cm/s, respectively). Further, addition of baPWV to Framingham Risk Score (FRS) improved the area under curve (AUC) for prediction of CHD from 0.676 to 0.728.24 Several clinical studies in eastern Asia have shown an association of baPWV with other intermediate CVD outcomes. For example, baPWV is reported to be positively associated with coronary stenosis in Korea,25–27 Japan,28 Taiwan,24 and China.29 Our sample population was healthier than these studies i.e. our sample was younger and population-based. Additionally, the mean baPWV in our population was less than the baPWV reported from these studies. Examining this association among healthy men allowed us to assess the utility of baPWV as an early marker of CVD in an asymptomatic population.
baPWV measures arterial stiffness over the central and peripheral arterial tree. In contrast, cfPWV – a widely accepted marker of arterial stiffness – primarily measure stiffness in the central aortic trunk. A higher proportion of smooth muscle cells in the peripheral arteries, as compared to that in the aorta, may be one reason for higher velocity of transmission of the pulse wave in the peripheral vasculature. If true, this may at least partly explain the increased PWV observed in the measurement of baPWV, as compared to the cfPWV. However, given that aorta forms a large portion of the arterial tree over which baPWV is measured, 58% of the variation in baPWV can be explained by aortic PWV.30 Further research is needed to examine pathogenesis of arterial stiffness especially in the peripheral muscular arteries.
Several factors may be responsible for the association between baPWV and coronary atherosclerosis as measured by CAC. Firstly, the pathogenesis of arterial stiffness possibly shares some common risk factors with atherosclerosis31,32 – this is more likely in the peripheral muscular arteries than in the central aortic trunk. We have previously shown that atherogenic lipoprotein particles are associated with baPWV and with femoral-ankle pulse wave velocity, but not with cfPWV.33 In this regard, ankle-brachial index, an established measure of peripheral arterial disease, is also shown to be associated with coronary atherosclerosis.34,35 Secondly, arterial stiffness increases the mechanical stress on the arterial wall. This triggers molecular cascades that further triggers the growth of microvasculature within the vessel walls, and ultimately leads to microvasculature remodeling and damage.36 These microscopic changes may be a fertile ground for the formation of atherosclerotic lesions. Finally, arterial stiffening reduces the cushioning effect of the aortic trunk that helps in maintaining coronary blood flow during the diastole. It increases cardiac afterload, thus increasing left-ventricular mass and requirement for coronary blood flow.37
baPWV has a potential for wide clinical application. A recent meta-analysis has reported that baPWV is an independent predictor of total cardiovascular events, cardiovascular mortality, and all-cause mortality. However, 17 out of 18 studies used in this meta-analysis were conducted in eastern Asia.6 baPWV measurement is highly reproducible, much less expensive than CT, can be performed in a physician’s office, requires little operator’s expertise, and does not require exposure to the inguinal area. Currently, it is widely used in clinics in Japan and South Korea to assess the risk of future CVD. However, several concerns need to be addressed before it can be used as a clinical tool in the West, most important of which are (1) determination of normal reference values, and (2) applicability among Western populations.
Our results should be interpreted in light of the study limitations. As our data are cross-sectional, we cannot determine temporality of the association between baPWV and CAC; a scenario in which CAC leads to increase in baPWV, however, seems unreasonable. Our results are not generalizable to older populations or to women as our sample consisted of middle-aged men within a relatively narrow age range. However, use of this sample population allows us to examine our hypothesis in the age-group in which baPWV is most likely to be useful as an early screening tool. We defined presence of CAC as ≥ 10 AU as CAC score between 0 and 10 is likely to be noise.16 We had few participants with clinically significant CAC (i.e CAC ≥400 AU) (n=19),38 and thus, could not test association of baPWV with clinically significant CAC. Limited sample size within each race/ethnicity limited our ability to perform multivariable adjustment in a race-specific analysis.
5.0 Conclusion
In a population-based sample of healthy middle-aged men without CVD, baPWV is independently associated with coronary atherosclerosis measured by CAC. This association is consistent among Whites and Blacks in the US. Longitudinal studies to examine ability of baPWV to predict coronary atherosclerosis and CVD events in the Western populations are needed.
Supplementary Material
Acknowledgments
Funding Source: This work was supported by grants HL068200 and HL071561 from the National Institutes of Health, Bethesda, MD, USA, Korea Center for Disease Control and Prevention (Government budget code: 2004-E71001-00, 205-E71001-00) and grants B 16790335, A 13307016, 17209023, 21249043, A 25253046 and B 23390174 from the Japanese Ministry of Education, Culture, Sports, Science and Technology (Tokyo, Japan).
Footnotes
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References
- 1.Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28–e292. doi: 10.1161/01.cir.0000441139.02102.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Heidenreich PA, Trogdon JG, Khavjou OA, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933–944. doi: 10.1161/CIR.0b013e31820a55f5. [DOI] [PubMed] [Google Scholar]
- 3.Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S49–S73. doi: 10.1161/01.cir.0000437741.48606.98. [DOI] [PubMed] [Google Scholar]
- 4.Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: A report of the american college of cardiology foundation/american heart association task force on practice guidelines. Circulation. 2010;122(25):e584–e636. doi: 10.1161/CIR.0b013e3182051b4c. [DOI] [PubMed] [Google Scholar]
- 5.Andersson C, Vasan RS. Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease?: clinical risk scores are sufficient to define primary prevention treatment strategies among asymptomatic patients. Circulation Cardiovascular imaging. 2014;7(2):390–397. doi: 10.1161/CIRCIMAGING.113.000470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Vlachopoulos C, Aznaouridis K, Terentes-Printzios D, Ioakeimidis N, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with brachial-ankle elasticity index: a systematic review and meta-analysis. Hypertension. 2012;60(2):556–562. doi: 10.1161/HYPERTENSIONAHA.112.194779. [DOI] [PubMed] [Google Scholar]
- 7.Yamashina A, Tomiyama H, Takeda K, et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertension research: official journal of the Japanese Society of Hypertension. 2002;25(3):359–364. doi: 10.1291/hypres.25.359. [DOI] [PubMed] [Google Scholar]
- 8.Brunner-La Rocca HP. Towards applicability of measures of arterial stiffness in clinical routine. Eur Heart J. 2010;31(19):2320–2322. doi: 10.1093/eurheartj/ehq211. [DOI] [PubMed] [Google Scholar]
- 9.Tomiyama H, Yamashina A. The application of brachial-ankle pulse wave velocity as a clinical tool for cardiovascular risk assessment. Hypertension. 2012;60(5):e40. doi: 10.1161/HYPERTENSIONAHA.112.201806. author reply e41. [DOI] [PubMed] [Google Scholar]
- 10.Venkitachalam L, Mackey RH, Sutton-Tyrrell K, et al. Elevated pulse wave velocity increases the odds of coronary calcification in overweight postmenopausal women. Am J Hypertens. 2007;20(5):469–475. doi: 10.1016/j.amjhyper.2006.11.006. [DOI] [PubMed] [Google Scholar]
- 11.Li S, Chen W, Srinivasan SR, Berenson GS. Influence of metabolic syndrome on arterial stiffness and its age-related change in young adults: the Bogalusa Heart Study. Atherosclerosis. 2005;180(2):349–354. doi: 10.1016/j.atherosclerosis.2004.12.016. [DOI] [PubMed] [Google Scholar]
- 12.Loehr LR, Snyder M, Selvin E, et al. Abstract P336: Diabetes and Impaired Fasting Glucose are Associated with Pulse Wave Velocity in Older Adults: the ARIC Study. Circulation. 2014;129(Suppl 1):AP336–AP336. [Google Scholar]
- 13.Sekikawa A, Ueshima H, Kadowaki T, et al. Less subclinical atherosclerosis in Japanese men in Japan than in White men in the United States in the post-World War II birth cohort. Am J Epidemiol. 2007;165(6):617–624. doi: 10.1093/aje/kwk053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kimoto E, Shoji T, Shinohara K, et al. Regional arterial stiffness in patients with type 2 diabetes and chronic kidney disease. Journal of the American Society of Nephrology: JASN. 2006;17(8):2245–2252. doi: 10.1681/ASN.2005101038. [DOI] [PubMed] [Google Scholar]
- 15.Choo J, Shin C, Barinas-Mitchell E, et al. Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study. BMC Cardiovasc Disord. 2014;14:5. doi: 10.1186/1471-2261-14-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Sekikawa A, Miura K, Lee S, et al. Long chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese men in Japan and white men in the USA: population based prospective cohort study. Heart. 2014;100(7):569–573. doi: 10.1136/heartjnl-2013-304421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827–832. doi: 10.1016/0735-1097(90)90282-t. [DOI] [PubMed] [Google Scholar]
- 18.Choo J, Ueshima H, Curb JD, et al. Serum n-6 fatty acids and lipoprotein subclasses in middle-aged men: the population-based cross-sectional ERA-JUMP study. The American journal of clinical nutrition. 2010;91(5):1195–1203. doi: 10.3945/ajcn.2009.28500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Fujiyoshi A, Sekikawa A, Shin C, et al. A cross-sectional association of obesity with coronary calcium among Japanese, Koreans, Japanese Americans, and U.S. whites. European heart journal cardiovascular Imaging. 2013;14(9):921–927. doi: 10.1093/ehjci/jet080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community a statement by the american society of hypertension and the international society of hypertension. J Hypertens. 2014;32(1):3–15. doi: 10.1097/HJH.0000000000000065. [DOI] [PubMed] [Google Scholar]
- 21.Myers GL, Cooper GR, Winn CL, Smith SJ. The Centers for Disease Control-National Heart, Lung and Blood Institute Lipid Standardization Program. An approach to accurate and precise lipid measurements. Clinics in laboratory medicine. 1989;9(1):105–135. [PubMed] [Google Scholar]
- 22.American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37 (Suppl 1):S81–90. doi: 10.2337/dc14-S081. [DOI] [PubMed] [Google Scholar]
- 23.Han C, Kronmal R. Box-Cox transformation of left-censored data with application to the analysis of coronary artery calcification and pharmacokinetic data. Statistics in medicine. 2004;23(23):3671–3679. doi: 10.1002/sim.1925. [DOI] [PubMed] [Google Scholar]
- 24.Liu CS, Li CI, Shih CM, et al. Arterial stiffness measured as pulse wave velocity is highly correlated with coronary atherosclerosis in asymptomatic patients. J Atheroscler Thromb. 2011;18(8):652–658. doi: 10.5551/jat.7021. [DOI] [PubMed] [Google Scholar]
- 25.Nam HJ, Jung IH, Kim J, et al. Association between brachial-ankle pulse wave velocity and occult coronary artery disease detected by multi-detector computed tomography. Int J Cardiol. 2012;157(2):227–232. doi: 10.1016/j.ijcard.2011.01.045. [DOI] [PubMed] [Google Scholar]
- 26.Seo WW, Chang HJ, Cho I, et al. The value of brachial-ankle pulse wave velocity as a predictor of coronary artery disease in high-risk patients. Korean Circ J. 2010;40(5):224–229. doi: 10.4070/kcj.2010.40.5.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Kwon JE, Mintz GS, Kim SW, et al. Relationship between coronary artery plaque composition by virtual histology intravascular ultrasound analysis and brachial-ankle pulse wave velocity in patients with coronary artery disease. Coron Artery Dis. 2011;22(8):565–569. doi: 10.1097/MCA.0b013e32834c5e6f. [DOI] [PubMed] [Google Scholar]
- 28.Imanishi R, Seto S, Toda G, et al. High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men. Hypertension Research. 2004;27(2):71–78. doi: 10.1291/hypres.27.71. [DOI] [PubMed] [Google Scholar]
- 29.Xiong Z, Zhu C, Zheng Z, et al. Relationship between arterial stiffness assessed by brachial-ankle pulse wave velocity and coronary artery disease severity assessed by the SYNTAX score. J Atheroscler Thromb. 2012;19(11):970–976. doi: 10.5551/jat.13326. [DOI] [PubMed] [Google Scholar]
- 30.Sugawara J, Hayashi K, Yokoi T, et al. Brachial-ankle pulse wave velocity: an index of central arterial stiffness? J Hum Hypertens. 2005;19(5):401–406. doi: 10.1038/sj.jhh.1001838. [DOI] [PubMed] [Google Scholar]
- 31.Yasmin, McEniery CM, Wallace S, Mackenzie IS, Cockcroft JR, Wilkinson IB. C-reactive protein is associated with arterial stiffness in apparently healthy individuals. Arterioscler Thromb Vasc Biol. 2004;24(5):969–974. doi: 10.1161/01.ATV.zhq0504.0173. [DOI] [PubMed] [Google Scholar]
- 32.Hall JE, Kuo JJ, da Silva AA, de Paula RB, Liu J, Tallam L. Obesity-associated hypertension and kidney disease. Curr Opin Nephrol Hypertens. 2003;12(2):195–200. doi: 10.1097/00041552-200303000-00011. [DOI] [PubMed] [Google Scholar]
- 33.Vishnu A, Choo J, Masaki KH, et al. Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study. J Hum Hypertens. 2014;28(2):111–117. doi: 10.1038/jhh.2013.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Allison MA, Laughlin GA, Barrett-Connor E, Langer R. Association between the ankle-brachial index and future coronary calcium (the Rancho Bernardo study) Am J Cardiol. 2006;97(2):181–186. doi: 10.1016/j.amjcard.2005.08.019. [DOI] [PubMed] [Google Scholar]
- 35.Papanas N, Tziakas D, Maltezos E, et al. Peripheral arterial occlusive disease as a predictor of the extent of coronary atherosclerosis in patients with coronary artery disease with and without diabetes mellitus. The Journal of international medical research. 2004;32(4):422–428. doi: 10.1177/147323000403200412. [DOI] [PubMed] [Google Scholar]
- 36.Safar M, O’Rourke MF. Arterial stiffness in hypertension. Vol. 23. Elsevier Health Sciences; 2006. [Google Scholar]
- 37.London GM, Guerin AP. Influence of arterial pulse and reflected waves on blood pressure and cardiac function. Am Heart J. 1999;138(3 Pt 2):220–224. doi: 10.1016/s0002-8703(99)70313-3. [DOI] [PubMed] [Google Scholar]
- 38.Blaha M, Budoff MJ, Shaw LJ, et al. Absence of coronary artery calcification and all-cause mortality. JACC. Cardiovascular imaging. 2009;2(6):692–700. doi: 10.1016/j.jcmg.2009.03.009. [DOI] [PubMed] [Google Scholar]
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