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In a prospective, single-center study of moderate size (n=298), Duprez et al. (2004) studied 206 male and 92 female healthy subjects with a mean age of 50 +/- 12 years. Noninvasive radial artery pressure waveforms were acquired with a piezoelectric transducer and analyzed for 1) diastolic indices of C1 and C2 from the CR-2000 CVProfilor, and 2) systolic indices of augmentation as defined by augmentation pressure (AP), augmentation index (AIx), and systolic reflective index (SRI = P2/P1). These indices were then correlated to each other as well as to individual traditional risk factors and the Framingham Risk Score. The results indicate that the diastolic indices were significantly and inversely correlated to systolic indices with C2 showing a stronger inverse association than C1. C2 and Alx were significantly correlated with height, weight, and body mass index in men but not in women. All indices correlated better to blood pressure in women than men. In women, only systolic indices were significantly correlated to HDL cholesterol and only diastolic indices were significantly correlated to LDL cholesterol. All indices were significantly correlated to the Framingham Risk Score, which was stronger in women then men, but when adjusted for age only diastolic indices remained significant in women.
The authors concluded that diastolic and systolic indices of pulse contour analysis correlate differently with traditional risk factors in men and women.
Wilson et al. (2004) compared small and large arterial elasticity (SAE/C2, LAE/C1), endothelial function as measured by flow mediated dilation (FMD), carotid intima-medial thickness (IMT), ankle brachial index (ABI), pulse pressure (PP) and pulse wave velocity (PWV) for assessing arterial function in low and high vascular disease risk groups. Twenty healthy subjects (HS) and 20 older subjects with type 2 diabetes mellitus (DM) were studied with all techniques at a single sitting by a single operator. C2 assessed by pulse wave analysis correlated with endothelial function measured by FMD in young apparently healthy subjects and older subjects with type 2 diabetes. Systolic BP and PP correlated with C2 and FMD in older diabetic subjects but not healthy subjects. The interrelationships between arterial function measures are different in high and low risk populations. This variability needs to be considered when applying these techniques to individuals in different populations.
Three prospective, multicenter studies, of moderate sample size (n=212, n=230, n=178), were conducted by the same research group and used the same study population of normotensive and hypertensive individuals. In these groups of individuals, blood pressure was measured using a mercury manometer and arterial compliance or elasticity was determined using the CVProfilor CardioVascular Profiling System. These parameters were measured in triplicate 3 minutes apart in a random sequence, with the patient in a supine position.
The objective of the first study was to determine arterial elasticity in normotensive and hypertensive individuals using the CVProfilor. An evaluation of large artery and small artery elasticity in 212 normotensives (with and without a family history of hypertension) and hypertensives (treated and controlled or untreated and uncontrolled) demonstrated that both large artery and small artery elasticity indices were significantly higher (PP=0.0001) across the four groups in these elasticity indices. As hypertension status worsened, large and small artery elasticity decreased, suggesting a potential for the diagnostic use of arterial elasticity determinations (Prisant, 2001a).
Cardiovascular Disease Risk Tests - Commercial Medical Management Guideline
The aim of the second study was to assess and compare the accuracy of sequential same arm blood pressure measurement by the mercury sphygmomanometer with oscillometric blood pressure measurements using the CVProfilor, which also determines arterial elasticity. Sequential single-arm blood pressure measurements performed in 230 normotensives and hypertensives (in which the sequence of testing was randomized) showed that the CVProfilor, which uses a dynamic linear deflation oscillometric method, measures blood pressure with reasonable agreement to that obtained manually using a mercury sphygmomanometer as reference method. For systolic and diastolic blood pressure, 60.9% and 70.4% of sequential measurements were within mm Hg, respectively, and 85.2% of systolic and 92.6% of diastolic blood pressure measurements were within mm Hg agreement (Prisant, 2001b).
The third study examined arterial elasticity by ethnicity in normotensive and hypertensive individuals to determine whether there were racial differences. An evaluation of large and small artery elasticity indices in 178 normotensives and hypertensives confirmed that these are reduced as hypertension status worsens. While age and height were important covariates of small and large artery elasticity, and hypertension status was a significant predictor of small and large artery elasticity, race was not found to be a significant predictor of either small or large artery elasticity. That is, large and small artery elasticity indices do not differ between white and black individuals with varying degrees of hypertension after adjusting for covariates (Prisant, 2002).
Carotid intima-media thickness Folsom et al. (2008) assessed whether maximum carotid intima-media thickness (IMT) or coronary artery calcium (CAC) is the better predictor of incident cardiovascular disease (CVD) in a prospective cohort study of subjects aged 45 to 84 years who were initially free of CVD (n = 6698). The main outcome measure was the risk of incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up. The investigators found that there were 222 CVD events during follow-up. Coronary artery calcium was associated more strongly than carotid IMT with the risk of incident CVD. The hazard ratio was only 1.2 for the association between carotid IMT and risk of incident CVD. A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of incident CVD than was IMT. The investigators concluded that although the use of bioimaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC score is a better predictor of subsequent CVD events than carotid IMT.
Lorenz et al. (2007) evaluated eight studies and concluded that CIMT is a strong predictor of future vascular events. The relative risk per CIMT difference is slightly higher for the end point stroke than for myocardial infarction. In future CIMT studies, ultrasound protocols should be aligned with published studies. Data for younger individuals are limited and more studies are required.
Brohall et al. (2006) performed a systematic review of 23 studies of CIMT that included patients with Type 2 diabetes.
They concluded that Type 2 diabetes was associated with a 0.13 mm increase in IMT compared with control subjects. In patients with IGT, the increase in CIMT was about one-third of that observed in diabetes. The observed difference in CIMT can be interpreted as if the diabetes patients were more than 10 years older than the control groups, and that the relative risks of myocardial infarction and stroke were increased by almost 40%, respectively.
Espeland et al. (2005) performed a meta-analysis of an unspecified number of studies that evaluated CIMT as a surrogate for clinical events in trials of HMG-CoA reductase inhibitors and concluded that CIMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials. This does not, however, establish that it may serve universally as a surrogate marker in trials of other agents.
Insufficient evidence exists to conclude that noninvasive arterial compliance testing, using waveform analysis, is effective in predicting risk for cardiovascular disease. There is inadequate clinical evidence from prospective studies that either arterial compliance testing or carotid intima-media thickness measurement alter patient management or improve clinical outcomes.
Cardiovascular Disease Risk Tests - Commercial Medical Management Guideline
Advanced lipoprotein analysis Apolipoproteins In review of the published, scientific literature there are inconsistent results with regards to the usefulness of apolipoprotein testing. Research has shown a lack of universal, standardized testing modalities and patient-selection criteria.
There are relatively few studies investigating the relationship between apoA-I and risk of coronary heart disease (CHD) and results of these studies are conflicting. There are even fewer studies investigating the effects of drug interventions on apo A-I levels in hypercholesterolemic patients. Additional large, prospective studies that include both men and women are needed to establish whether measurement of apo A-I will be more predictive of CHD than conventional lipid risk factors.
The MONICA/KORA Augsburg cohort study included 1414 men and 1436 women aged 35 to 64 years. It concluded that the predictive power of the apoB/apoA-I ratio was similar to that of the total cholesterol/HDL cholesterol ratio in men and women (Meisinger 2004).
The studies that evaluated the association of apo B with CHD, with the exception of the early report from the Physicians' Health Study, were, for the most part, positive studies. While there is some evidence from these studies that apo B levels, either singularly or in combination with other metabolic abnormalities, may be more predictive of CHD risk than conventional risk factors such as low-density lipoprotein cholesterol (LDL-C) and the ratio of total cholesterol to HDL-C, for most patient groups these results need confirmation in additional, large, prospective studies. However, there is strong evidence from the very large AFCAPS/TexCAPS trial that in certain patient groups, such as those with average total cholesterol and LDL-C levels and low HDL-C levels, apo B may be a more accurate predictor of CHD than LDL-C. The intervention studies established that lipid-lowering therapy produces angiographic benefits as well as reductions in clinical cardiovascular events. Moreover, there was some evidence that therapy reduces levels of apo B and apo Bcontaining lipoproteins. Evidence from one small intervention study suggested that patients with elevated apo B levels and lower LDL-C levels may benefit from lipid-lowering therapy, confirming the results of the AFCAPS/TexCAPS trial (Gotto et al. 2000). However, these results also need confirmation in additional, larger, prospective, longer-term studies.
The large population for the Apolipoprotein-related Mortality Risk Study (AMORIS) included 175,553 Swedish men and women. This study evaluated if apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) can better predict the risk of acute myocardial infarctions (MI) than the conventional risk factor analysis of total cholesterol, triglycerides, and LDLcholesterol measurements. The study reported that total cholesterol, triglycerides, apoB and apoB/apoA-1 ratio were strong positive predictors of increased risk of fatal MI in both men and women. ApoB proved to be a stronger predictor of cardiac risk than LDL-cholesterol, but there may have been a methodological error in the calculation of LDLcholesterol in the study. The study outcome suggests that the measurement of apoB, apoA-1 and the apoB/apoA-1 ratio could improve the prediction of cardiac risk and be useful in the assessment of risk and decision making of initiating lipid-lowering treatment (Walldius 2001).
Lipoprotein (a) There are three requirements for Lp(a) testing to be of value for risk prediction and patient management: 1) standardization of Lp(a) assays, 2) development of additional treatments to reduce Lp(a) levels, and 3) intervention trials to establish the benefit of Lp(a) reduction. Future research must investigate further the interactions of Lp(a) with other CHD risk factors and the value of using the combination of Lp(a) and other risk factors to predict risk and manage patients.
There have been many studies investigating the relationship between Lp(a) and CHD. In some studies, risk of disease was increased by the interaction of Lp(a) with other lipid factors. A cross-sectional analysis of 750 men and 403 women Cardiovascular Disease Risk Tests - Commercial Medical Management Guideline concluded that, although neither Lp(a) nor homocysteine were individually associated with risk of CHD in women, the two factors interacted to increase risk; and the size of this effect was greater than what would be expected if the risk factors were operating either additively or exponentially. In men, both elevated Lp(a) and homocysteine appeared to be independent risk factors for CHD, but the presence of both factors did not confer additional risk (Foody, 2000).
The PRIME study was a prospective five-year cohort study of 9,133 French and Northern Irish men who were between the ages of 50-59 at the start of the study, had no history of coronary heart disease and were not on any lipid lowering drug therapy. On entry in the study, the Lp(a) was measured along with other traditional laboratory cardiovascular risk factors such as LDL and HDL cholesterol, and triglycerides. Previous comparisons of different studies looking at the relationship of Lp(a) and CHD were inconsistent due to various procedures for determining plasma Lp(a) and the absence of standardization of Lp(a) measurement. In the study, the measurements of Lp(a) were all performed in the same laboratory with fresh plasma. The authors reported the association between Lp(a) and CHD to be independent of other risk factors but that there was also a significant interaction between high levels of Lp(a) and increasing LDL-cholesterol.
The study results concluded that Lp(a) was significant in predicting increased risk of myocardial infarction and angina pectoris (Luc 2002).
The Atherosclerosis Risk in the Communities (ARIC) Study reported a follow-up after ten years in which 725 coronary heart disease (CHD) events occurred in 12,339 middle-aged participants who were initially identified as free of CHD.