Therefore, all these variables were included in the core model where sex, heart rate, height, and cSBP were strongly associated with AIx (all P < 0.001). Focusing on ethnicity, Indian and Pakistani/Bangladeshi continued to have significantly higher AIx values compared with other groups after fully adjusting for confounding factors (respective β = 3.35 and 4.20, both P < 0.005; Table 2). AIx was also borderline significantly higher in Black African (β = 2.65, P = 0.047), including adjustments for childhood variables, and only in Black Caribbean it remained marginally but not significantly higher than in White UK peers.
No influence was detectable for body composition parameters or ‘fat’ such as BMI (P = 0.5), waist-to-height ratio (P = 0.4) or overweight status (P = 0.2) so these were not included in the core model. Regarding BP, DBP (P = 0.001), mean arterial pressure (MAP; P = 0.025), cSBP (P < 0.001) but not brachial SBP (P = 0.679) were positively related to AIx; using MAP instead of cSBP in the core model (not shown) did not change any correlations. Psychosocial or deprivation measures also were not correlated with AIx (and their inclusion did not change any previous associations); further adjustments of the core model for 11–13 years variables only found a borderline (negative) association with adolescent MAP (P = 0.055).
The present study showed clear ethnic differences in AIx, considered an index of wave reflection, in a multiethnic cohort living in similar areas, addressing an issue on which little is published.
Previous small studies in adults showed conflicting results regarding ‘White’ and ‘Black’ young adults in the United States and Europe, respectively [25,26]. Another found that differences in AIx between 94 East Asian and 47 age-matched White peers disappeared after adjusting for height . In large population-based studies throughout the world (10 550 adults), after adjustment for age, heart rate, MAP, and body size, black Africans had markedly higher AIx than British Whites . In 2057 adults aged 21–90 years with type 2 diabetes in the multiethnic state of Singapore, AIx was significantly higher in Indians (28.1 ± 10.8%) than Chinese (26.1 ± 10.7%, P < 0.002) . Epidemiological data in the same area found that CHD and mortality was higher in the Indian population compared with the Chinese one [30,31] supporting the idea that arterial stiffness and wave reflection may, at least partially, underlie the differences in such adverse outcome.
In our multi ethnic cohort living in the London area, PWV was similar or lower in ethnic minorities compared with White UK , whereas AIx was significantly higher in Indian and Bangladeshi/Pakistani than White UK even after adjustment for confounding factors (sex, heart rate, height, and cSBP, – Table 2). These results may suggest that the parameter of wave reflection, particularly in young South Asian individuals, could indicate important ethnic differences in central hemodynamics, which cannot be fully assessed with conventional sphygmomanometry.
Previously, the general view has been that brachial BP outcomes were ‘more severe’, or ‘worse’ in black populations, even at given levels of BP. However, there remains some doubt whether this is and was so in unbiased genuinely representative population samples (now difficult to find) or after full adjustment for increased hypertension prevalence and other, including social, factors. That view, long considered here [32,33], was substantiated in the long-term follow-up of US studies , and recently in the long-term UK ‘SABRE’ study . In the latter three-dimensional echo study, cardiac remodeling rather than hypertrophy was found to be the main issue.
It seems possible that wave reflections, here as AIx, may contribute to the development of left ventricular hypertrophy or ’remodeling’ and could explain the higher rates of hypertensive target organ damage in some ethnic minorities, as was found in African-Americans and in African-Caribbeans in Britain [36–38]. Left ventricular hypertrophy in nonathletic people reflects subclinical organ damage and is very likely an early indicator of cardiovascular, especially hypertensive heart disease.
Taking these considerations together, it seems that in ethnic minorities, and particularly in South Asians, increased central wave reflection from early adulthood could be a determinant of target organ damage before the onset of other well established risk factors.
In such context, discrepancy between the results of PWV and AIx is not surprising as AIx is not a surrogate marker of PWV . Rather, as a measure of arterial wave reflection, it probably depends both on the speed of the pressure wave and on anatomical and mechanical characteristics of the arterial tree. These latter characteristics may be influenced by the vascular tone of the small muscular arteries and arterioles rather than by the elastic properties of the aorta .
In our analysis, SBP was not correlated with AIx, likely in part explained by characteristic aortic pressure amplification in young people. In the elderly, the reflected waves return to the aorta during systole, thereby increasing SBP and pulse pressure; in contrast, in younger people, reflected pulse waves return during diastole, resulting in an increase in mean DBP .
Thus, in our final model we used only cSBP and MAP. Having outlined these concepts, some traditional some not, we should say that the origins of the ‘augmentation’ are by no means certain. Both amplified Windkessel-like effects and excess (aortic) ‘reservoir’ pressure may be additional, or even replacement, causes of these apparent wave reflections [42,43]. Recently, in patients undergoing cardiac catheterization the reduction in augmentation pressure after nitroglycerin administration was, at least in part, dependent on ventricular contraction/relaxation dynamics rather than reflection effects .
In the core model, no ‘fat parameters’ were added because of lack of significant correlation in univariate analysis. Although arterial stiffness and vascular remodeling are generally greater in obese compared with nonobese individuals , this may be because of co-occurrence of cardiovascular risk factors rather than obesity per se. DeVallance et al. found in a small population (102 adults) without type 2 diabetes and CVD that AIx increased in men but decreased in women with increasing BMI; contrarily, in a diabetic cohort, no correlation was found between BMI and augmentation pressure .
Psychosocial or deprivation measures did not show any correlation with AIx (and their inclusion in the model did not change any previous associations); further adjustments of the core model for 11–13 years variables only underlined a borderline (negative) association with adolescent MAP (P = 0.055).
Beneficial effects of physical activity on arterial stiffness are found, and across various populations [48–50], probably related to arterial stiffening resulting from both passive (increased intima–media thickness) and active (smooth vascular muscle tone) components, both of which can be altered by physical activity . However, our results for AIx are in line with the Framingham analysis (2376 participants, mean age 47 years)  which did not show any effect of physical activity, measured continuously for 8 days, on AIx nor on flow-mediated dilatation. Those data suggest that physical activity could be associated with attenuated age-related increases in intima–media thickness, with very small effects on the active components of vascular muscle tone and endothelial dysfunction. These suggestions again need further investigation in younger people, free from CVD.
In conclusion, a multiethnic cohort of young adults living in the same area both PWV and AIx showed ethnic differences; however, only AIx was higher in ethnic minorities compared with White UK. These data suggest that parameters of wave reflection, rather than arterial stiffness, may underlie ethnic differences at this age and could be a useful tool for testing components of excess cardiovascular risk.
Limitations include a relatively small sample size (about 100 per ethnic group, balanced by sex, and smaller numbers with physical activity measured) and its cross-sectional nature so far.
Another is how far AIx is a measure of reflection as there may be components of arterial compliance and reservoir function as well as or rather than wave reflection per se. A study comparing the relationship between carotid AIx and wave reflection indices from wave intensity and wave separation analysis across adult ages in 65 healthy people suggested AIx gave misleading result, especially for its negative values . However, this analysis was a relatively small sample (n = 65) done on carotid arteries.
Relatively little data on prognostic value of PWV and AIx measured with Arteriograph device are available. Only a few follow-up studies evaluated prediction by the Arteriograph's stiffness and wave reflection parameters on cardiovascular events or mortality with conflicting results. Akkus et al. reported that arterial stiffness and wave reflection measured by it can predict further cardiovascular events in patients after myocardial infarction and the same group  showed that AIx and PWV predicted mortality independent of other variables in a small population of advanced heart failure patients. A follow-up study in CKD found no prognostic value for Arteriograph PWV and AIx on cardiovascular mortality in hemodialysis .
The prognostic value of PWV and AIx measured with oscillometric devices in a wider range of clinical conditions and in young populations free from CVD are needed.
We acknowledge the invaluable support of participants and their parents, the Participant Advisory Group, schools, civic leaders, local GP surgeries and community pharmacies, the Clinical Research Centre at Queen Mary University of London, the Clinical Research Facility at University College Hospital, the survey assistants and nurses involved with data collection, the Primary Care Research Network, and Professors Sanders and Cruickshank at the Diabetes and Nutritional Sciences Division at Kings College London for hosting the feasibility study. S.H. is the principal investigator of DASH. All authors contributed to study design, analyses, and writing of the article. The study was funded by the Medical Research Council (MC_U130015185/MC_UU_12017/1/MC_UU_12017–13.), Chief Scientist Office (SPHSU13) and North Central London Research Consortium and the Primary Care Research Network.
The study was funded by the MRC (MC_U130015185/MC_UU_12017/1-13), Chief Scientist Office (SPHSU13), North Central London Research Consortium and the Primary Care Research Network.
There are no conflicts of interest.
Reviewers’ Summary Evaluations
Strengths: 1. Population-based sample participating in the Determinants of Adolescent Social well being and Health (DASH); 2. The study assesses central SBP and augmentation index as potential precursors of greater risk in minority populations vs. the white majority; 3. The authors identify clear differences in augmentation index between South Asian populations and White UK youth.
Weaknesses: 1. Relatively limited number of youth in each group studied (∼100); 2. Absence of target organ data, e.g. LVH, carotid intimal–media thickness. Clinical events would not be expected in this young population.
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