Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors.

Little is known about how aortic waveform parameters vary with ethnicity and lifestyle factors. We investigated these issues in a large, population-based sample. We carried out a cross-sectional analysis of 4798 men and women, aged 50-84 years from Auckland, New Zealand. Participants were 3961 European, 321 Pacific, 266 Maori and 250 South Asian people. We assessed modifiable lifestyle factors via questionnaires, and measured body mass index (BMI) and brachial blood pressure (BP). Suprasystolic oscillometry was used to derive aortic pressure, from which several haemodynamic parameters were calculated. Heavy alcohol consumption and BMI were positively related to most waveform parameters. Current smokers had higher levels of aortic augmentation index than non-smokers (difference=3.7%, P<0.0001). Aortic waveform parameters, controlling for demographics, antihypertensives, diabetes and cardiovascular disease (CVD), were higher in non-Europeans than in Europeans. Further adjustment for brachial BP or lifestyle factors (particularly BMI) reduced many differences but several remained. Despite even further adjustment for mean arterial pressure, pulse rate, height and total:high-density lipoprotein cholesterol, compared with Europeans, South Asians had higher levels of all measured aortic waveform parameters (for example, for backward pressure amplitude: ß=1.5 mm Hg; P<0.0001), whereas Pacific people had 9% higher loge (excess pressure integral) (P<0.0001). In conclusion, aortic waveform parameters varied with ethnicity in line with the greater prevalence of CVD among non-white populations. Generally, this was true even after accounting for brachial BP, suggesting that waveform parameters may have increased usefulness in capturing ethnic variations in cardiovascular risk. Heavy alcohol consumption, smoking and especially BMI may partially contribute to elevated levels of these parameters.

Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease.

AIMS/HYPOTHESIS: A high prevalence of diabetes contributes to excess CHD in Indian Asians, but the underlying mechanisms are unclear. Heart rate, heart rate variability (HRV) and baroreflex sensitivity (BRS) are measures of cardiac autonomic function that are disturbed by hyperglycaemia and predict CHD. We compared these measures in Indian Asians and Europeans, and sought explanations for the observed differences. METHODS: A representative sample of 149 Europeans and 151 Indian Asians was recruited from primary care, 66% of them men (aged 35-75 years), 34% women (aged 55-75 years). Heart rate, HRV, BRS and cardio-metabolic profiles were measured over four successive 5 min periods with continuous ECG and blood pressure monitoring. RESULTS: Indian Asians were hyperglycaemic compared with Europeans (HbA(1c) (mean +/- SD) 6.5 +/- 1.2% vs 5.9 +/- 1.0%, p = 0.001). They had shorter mean RR intervals ((mean +/- SE) 969 +/- 13 vs 1,022 +/- 12 ms, p = 0.002), lower total RR interval power ((geometric mean, 95% CI) 925 [796-1075] vs 1,224 [1,064-1,422] ms(2), p = 0.008) and lower BRS ((mean +/- SE) 5.7 +/- 1.0 vs 6.6 +/- 1.0 ms/mmHg, p = 0.01). All measures of cardiac autonomic dysfunction were significantly associated with hyperglycaemia (mean RR interval vs HbA(1c) r = -0.22; p < 0.001). Ethnic differences in cardiac autonomic function persisted after adjustment for age, blood pressure and medication (mean RR interval 973 vs 1,021 ms, p = 0.004), but were attenuated or abolished by adjusting for HbA(1c) (979 vs 1,014 ms, p = 0.06) or other markers of hyperglycaemia. CONCLUSIONS/INTERPRETATION: Indian Asians from the general population have impaired cardiovascular autonomic function compared with Europeans. This is due to greater hyperglycaemia in Indian Asians and may determine their increased CHD risk.

Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.

BACKGROUND: Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. METHODS: Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. RESULTS: Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. CONCLUSIONS: Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs. MATERIALS AND METHODS: A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi-slice computerized tomography (CT), carotid and femoral intima-media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non-senescent EPCs (ns-EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry. RESULTS: Individuals with femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects. CONCLUSION: The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk.

Various issues relating to computational fluid dynamics simulations of carotid bifurcation flow based on models reconstructed from three-dimensional ultrasound images.

Computational fluid dynamics (CFD) flow simulation techniques have the potential to enhance understanding of how haemodynamic factors are involved in atherosclerosis. Recently, three-dimensional ultrasound has emerged as an alternative to other three-dimensional imaging techniques, such as magnetic resonance angiography (MRA). The method can be used to generate accurate vascular geometry suitable for CFD simulations and can be coupled with Doppler ultrasound to provide physiologically realistic flow boundary conditions. However, there are various ways to utilize the flow data acquired, possibly leading to different results regarding both flow and wall shear stress patterns. A disadvantage of three-dimensional ultrasound for imaging the carotid bifurcation has been established as being the scanning limitation of the jawbone position. This may make artificial extensions of the internal and/or external carotid arteries necessary, which in turn may influence the predicted flow patterns. Flow simulations were carried out for three outflow calculation schemes as well as four geometries with different extensions to the carotid daughter vessels. It was found that variation of flow patterns was more strongly influenced by the outflow conditions than by the extensions of the daughter vessels. Consequently, it is recommended that for future CFD simulations of carotid flow using three-dimensional ultrasound data, the outflow boundary conditions should rely on the most accurate measurement available, and flow data recorded in the common and internal carotid are considered more reliable than data from the external carotid. Even though the extended lengths of the daughter vessels have insignificant effects on the predicted haemodynamic parameters, it would be a safer option to extend the internal carotid by approximately three times the diameter of the common carotid artery.

Effect of tumour necrosis factor-alpha and interleukin 1beta on endothelium-dependent relaxation in rat mesenteric resistance arteries in vitro.

1. Pre-eclampsia is associated with elevated proinflammatory cytokine levels and endothelial dysfunction. This study examined the effect of two cytokines, tumour necrosis factor-alpha (TNF) and interleukin-1beta (IL-1) on endothelium-dependent relaxation in response to acetylcholine (ACH), bradykinin (BK) and histamine (HIS) in rat mesenteric small arteries in vitro. 2. Rat mesenteric arteries were mounted in an isometric myograph. Tone was induced with phenylephrine (PE) or a depolarizing solution containing 80 mM KCl (K(80)). Relaxation was measured in response to ACH, BK, HIS and sodium nitroprusside (SNP), an endothelium-independent relaxant. Inhibition of NO synthase by a combination of N(omega)-monomethyl-L-arginine (L-NMMA) and N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly inhibited relaxation in response to ACH and BK. Addition of an inhibitor of cyclooxygenase, indomethacin, had no additional effect when added to L-NMMA and L-NAME. Inhibition of endothelium-derived hyperpolarizing factor (EDHF) by K(80) partially reduced responses to ACH and BK. Inhibition of HIS-induced relaxation was more marked with K(80). L-NMMA and L-NAME largely abolished the remaining relaxation to ACH, BK and HIS in arteries contracted with K(80). 3. Preincubation with TNF for 30 min caused an inhibition of relaxation in response to ACH and BK in arteries contracted with PE. Responses to HIS and SNP were not affected by TNF under these conditions. TNF also inhibited ACH-induced relaxation in arteries contracted with K(80). IL-1 had no effect on responses to ACH and the combination of TNF and IL-1 was not more effective than TNF alone. 4. The inhibitory effect of TNF on ACH-induced relaxation was abolished by coincubation with superoxide dismutase (SOD) and was not seen if NO synthase was inhibited by L-NMMA and L-NAME. 5. TNF inhibits the NO-dependent component of endothelium-dependent relaxation in response to ACH and BK, but does not inhibit the EDHF-dependent component. This effect may be attributable to the ability of TNF to increase levels of superoxide anions (O(2)(-)) and the ability of O(2)(-) to inactivate NO. This mechanism could contribute to the endothelial dysfunction seen in situations where TNF is elevated, such as pre-eclampsia.

Reproducibility study of magnetic resonance image-based computational fluid dynamics prediction of carotid bifurcation flow.

The importance of shear stress in the initiation and progression of atherosclerosis has been recognized for some time. A novel way to quantify wall shear stress under physiologically realistic conditions is to combine magnetic resonance imaging (MRI) and computational fluid dynamics. The present study aims to investigate the reproducibility of the simulated flow by using this combined approach. The right carotid bifurcations of eight healthy subjects were scanned twice with MRI within a few weeks. Three-dimensional geometries of the vessels were reconstructed for each scan and each subject. Pulsatile flows through these models were calculated to assess errors associated with the predicted flow parameters. This was done by comparing various wall shear stress indices, including the time-averaged wall shear stress (WSS), oscillating shear index (OSI), WSS Gradients (WSSG) and WSS Angle Deviation (WSSAD). Qualitatively, all the wall shear parameters proved to be highly reproducible. Quantitatively, the reproducibility was over 90% for OSI and WSSAD, but less impressive (60%) for other parameters. Our results indicated that WSS and WSSG values were extremely sensitive to subtle variations in local geometry and mesh design, particularly in regions around the bifurcation apex where WSS values were high and least reproducible.

Carotid geometry reconstruction: a comparison between MRI and ultrasound.

Image-based Computational Fluid Dynamics (CFD) has become a popular tool for the prediction of in vivo flow profiles and hemodynamic wall parameters. Currently, Magnetic Resonance Imaging (MRI) is most widely used for in vivo geometry acquisition. For superficial arteries such as the carotids and the femoral artery, three-dimensional (3-D) extravascular ultrasound (3-DUS) could be a cost-effective alternative to MRI. In this study, nine healthy subjects were scanned both with MRI and 3-DUS. The reconstructed carotid artery geometries for each subject were compared by evaluating cross-sectional areas, centerlines, and carotid nonplanarity. Lumen areas agreed very well between the two different acquisition techniques, whereas centerlines and nonplanarity parameters showed measurable disagreement, possibly due to the different neck and head positions adopted for 3-DUS versus MRI. With the current level of agreement achieved, 3-DUS has the potential to become an inexpensive and fast alternative to MRI for image-based CFD modeling of superficial arteries.