Comparison of utility of arterial stiffness parameters for predicting cardiovascular events in the general population.

Several recent studies have suggested that arterial stiffness parameters such as peripheral pulse pressure (PPP), central blood pressure (CBP), and pulse wave velocity (PWV) are more accurate markers than brachial blood pressure for prediction of cardiovascular (CV) events. However, it remains unknown which arterial stiffness parameter is the most useful for predicting CV risk in the general population. Participants in the present study were randomly selected from the 40 to 79 year age group in the general population (n = 973; mean age, 59). PPP was determined in the upper arm with an oscillometric device. CBP was estimated noninvasively by radial pulsatile analysis, and brachial-ankle PWV was measured using a validated automatic device. A follow-up survey assessing the incidence of CV events including CV death was carried out after the baseline study. The mean follow-up duration was 7.8 years. Subjects were divided into quartiles according to PPP, CBP, or PWV. Event-free rates among the PWV quartiles were clearly divergent (P < 0.001); however, the rates among quartiles for the other parameters were not significant. In a multivariate Cox regression model, both the 90th percentile level of PWV (HR = 2.51, 95% CI; 1.21 - 5.22: P = 0.014) and the increase in PWV per one standard deviation (HR = 1.42, 95% CI; 1.06 - 1.90: P = 0.019) were significantly associated with risk of CV events. The area under the curves of the receiver operating characteristics analysis for CV event prediction of PWV was significantly larger than the others (P = 0.002 versus PPP; P = 0.043 versus systolic CBP). The measurement of brachial-ankle PWV is more useful than determination of PPP or CBP for identifying subjects at high risk of CV events within the general population.

Association between serum C-reactive protein levels and pulse wave velocity: a population-based cross-sectional study in a general population.

Arterial stiffness as determined by aortic pulse wave velocity (PWV) has been shown to predict cardiovascular events in high-risk subjects such as those with hypertension or end-stage renal disease. Although it is suspected that low-grade inflammation as represented by increased C-reactive protein (CRP) plays an important role in the progression of atherosclerosis, it is not yet known whether serum CRP levels are associated with PWV. To examine the relationship between brachial-ankle PWV (baPWV) and serum CRP levels, several cardiovascular risk factors including these two markers (baPWV and CRP) were measured in 870 participants (mean age 59 years) randomly selected from a general population. Age, male gender, systolic blood pressure, heart rate, diabetes, and serum CRP levels increased with the quartiles divided by baPWV (all, p<0.01). By multiple regression analysis, age (p<0.001), systolic blood pressure (p<0.001), heart rate (p<0.001), body mass index (p<0.001), and CRP (p<0.01) were significant and independent predictors for baPWV. In conclusion, this cross sectional study has demonstrated in the general population that the arterial stiffness marker baPWV was independently correlated with serum CRP levels after adjustment for other established cardiovascular risks factors. This result suggests that baPWV may be a surrogate marker for atherosclerotic vascular damages including an inflammatory component.

Relation between stent thrombosis and calcium channel blocker after drug-eluting stent implantation: Kumamoto Intervention Conference Study (KICS) registry.

BACKGROUND: Stent thrombosis (ST) has emerged as a severe complication of percutaneous coronary intervention (PCI). Since the occurrence of ST is lower in Japan than Western countries, there are few data to predict ST after drug-eluting stent (DES) implantation in Japan. We examined the independent predictors of ST incidence after DES implantation in Japanese patients, including the use of calcium channel blockers (CCBs). METHODS AND RESULTS: We used data from the Kumamoto Intervention Conference Study registry. There were 6286 consecutive patients enrolled from June 2008 to March 2011. Among them, we analyzed 3493 patients who underwent DES implantation. The incidence of definite/probable ST throughout a median follow-up period of 364 days was 0.57% (20 patients). There were 8 patients with early ST (within 30 days), 8 patients with late ST (between 31 and 365 days), and 4 patients with very late ST (after 1 year). The frequency of CCB use was significantly lower in ST than non-ST patients (25.0% versus 51.4%, respectively, p=0.016). Multiple regression analysis showed that longer stent length (p=0.034), acute coronary syndrome (p=0.039), and the absence of CCB use (p=0.046) were significant and independent predictors of ST within 1 year. CONCLUSIONS: These results suggest that CCB use may be associated with a decreased risk of ST after DES implantation within 1 year in Japanese patients.

The limited value of plasma B-type natriuretic peptide for screening for left ventricular hypertrophy among hypertensive patients.

BACKGROUND: Several reports have suggested that plasma B-type natriuretic peptide (BNP) levels are elevated in hypertensive patients especially with left ventricular (LV) hypertrophy. However, few data have been available concerning the utility of plasma BNP measurement to identify LV hypertrophy in hypertensive patients in a general population screening context. METHODS: We measured plasma BNP concentrations in 1112 volunteers in a health screening program (mean age, 57 years). All subjects underwent electrocardiography, chest X-ray, and echocardiography. Among the sample, 284 subjects were designated as hypertensive because they were on antihypertensive drugs or showed elevated systemic blood pressure. By echocardiography, 36 of the hypertensive patients showed significant LV hypertrophy. RESULTS: There were no significant differences in age and sex between the LV hypertrophy and non-LV hypertrophy groups. Plasma BNP levels in the LV hypertrophy group were significantly higher than in the non-LV hypertrophy group (19.4 +/- 18.9 v 28.2 +/- 28.2 pg/mL; P <.05). However, the ability of plasma BNP levels to discriminate between LV hypertrophy and non-LV hypertrophy patients was not sufficient as the area under the receiver operating characteristic curve was 0.588 (95% CI: 0.528-0.646) with sensitivity of 50.0% and specificity of 69.0%. Positive and negative predictive values for detecting LV hypertrophy among hypertensive patients were 18.9% and 90.5%, respectively. This ability did not improve significantly when the screening was limited to patients with untreated LV hypertrophy or concentric LV hypertrophy. CONCLUSIONS: Plasma BNP testing in a mass screening setting is of limited use for the identification of LV hypertrophy patients among hypertensive patients with heterogeneous etiology.

Comprehensive analysis of intravascular ultrasound and angiographic morphology of culprit lesions between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Some plaques lead to ST-segment elevation myocardial infarction (STEMI), whereas others cause non-ST-segment elevation acute coronary syndrome (NSTEACS). We used angiography and intravascular ultrasound (IVUS) to investigate the difference of culprit lesion morphologies in ACS. METHODS: Consecutive 158 ACS patients whose culprit lesions were imaged by preintervention IVUS were enrolled (STEMI=81; NSTEACS=77). IVUS and angiographic findings of the culprit lesions, and clinical characteristics were compared between the groups. RESULTS: There were no significant differences in patients' characteristics except for lower rate of statin use in patients with STEMI (20% vs 44%, p=0.001). Although angiographic complex culprit morphology (Ambrose classification) and thrombus were more common in STEMI than in NSTEACS (84% vs 62%, p=0.002; 51% vs 5%, p<0.0001, respectively), SYNTAX score was lower in STEMI (8.6 ± 5.4 vs 11.5 ± 7.1, p=0.01). In patients with STEMI, culprit echogenicity was more hypoechoic (64% vs 40%, p=0.01), and the incidence of plaque rupture, attenuation and "microcalcification" were significantly higher (56% vs 17%, p<0.0001; 85% vs 69%, p=0.01; 77% vs 61%, p=0.04, respectively). Furthermore, the maximum area of ruptured cavity, echolucent zone and arc of microcalcification were significantly greater in STEMI compared with NSTEACS (1.80 ± 0.99 mm(2) vs 1.13 ± 0.86 mm(2), p=0.006; 1.52 ± 0.74 mm(2) vs 1.21 ± 0.81 mm(2), p=0.004; 99.9 ± 54.6° vs 77.4 ± 51.2°, p=0.01, respectively). Quantitative IVUS analysis showed that vessel and plaque area were significantly larger at minimum lumen area site (16.6 ± 5.4 mm(2) vs 14.2 ± 5.5 mm(2), p=0.003; 13.9 ± 5.1 mm(2) vs 11.6 ± 5.2 mm(2), p=0.003, respectively). CONCLUSION: Morphological feature (outward vessel remodeling, plaque buildup and IVUS vulnerability of culprit lesions) might relate to clinical presentation in patients with ACS.

Association of decreased variation of R-R interval and elevated serum C-reactive protein level in a general population in Japan.

Several studies have suggested that an increased high sensitivity C-reactive protein (hsCRP) level is a strong independent predictor of increased risk for atherosclerotic cardiovascular mortality and morbidity. Reduced heart rate variability (HRV) has also been reported to predict cardiovascular events such as sudden death and myocardial infarction in apparently healthy subjects. The aim of this cross-sectional study was to test the possible correlation between variation of the R-R interval as one of the markers of HRV and serum hsCRP levels in a general population in Japan. Resting, supine, 2-minute, beat-to-beat heart rate data were collected in 823 randomly selected participants enrolled in our cohort study. The coefficient of variation of the R-R interval (CVrr) was obtained as a parameter of HRV. To determine which factors predict the presence of low CVrr (below the 5 percentile) in this group, we performed a multivariate logistic regression analysis using cardiovascular risk factors and an elevated hsCRP level as independent variables. The lowest CVrr group showed significantly higher hsCRP levels compared to those of other quartiles (P < 0.01). After adjustment for confounding factors such as age, heart rate, obesity, hypercholesterolemia, and hypertension by multivariate logistic analysis, an elevated hsCRP level (OR = 3.11, 95%CI; 1.27-7.60: P < 0.02) was a significant independent predictor of low CVrr. The results of the present study indicate that an increased serum hsCRP level is significantly associated with reduced CVrr in this general population. It is conceivable that the parasympathetic nerve withdrawal and inflammation could interact with each other, resulting in the progression of atherosclerotic cardiovascular disease.

B-type natriuretic peptide testing for structural heart disease screening: a general population-based study.

BACKGROUND: Several types of structural heart disease are important precursors for congestive heart failure or cardioembolic stroke. We have previously demonstrated that plasma B-type natriuretic peptide (BNP) measurement is useful for detection of structural heart disease in a multiphasic health screening setting. To extend our hypothesis to the general population, the utility of BNP testing for identifying structural heart disease was assessed in a general population and in subgroups divided by sex, age, and presence/absence of risk factors. METHODS AND RESULTS: This cross-sectional cohort study measured plasma BNP concentrations in 993 randomly selected community-dwelling adults (mean age 58 years). All subjects underwent plasma BNP measurement and transthoracic echocardiography. Using prejudged criteria, 41 subjects were diagnosed to have some form of structural heart disease (mild left ventricular systolic dysfunction in 11, valvular heart disease in 9, hypertensive heart disease in 3, hypertrophic cardiomyopathy in 2, ischemic heart disease in 2, lone atrial fibrillation in 14). The utility of BNP testing was evaluated by receiver operating characteristic (ROC) analysis and by cost analysis for detection of 1 case within each subgroup of the cohort. Overall, the sensitivity and specificity of BNP testing for identification of structural heart disease were 61% and 92%, respectively. The area under the ROC curve was 0.77 (95% CI; 0.74-0.79). When sex-specific ROC analyses were performed, sensitivity and specificity were 61% and 91% in men, and 50% and 95% in women, respectively. Although the performance of BNP testing on the basis of these figures might be suboptimal, efficacy was improved in subgroups with a high prevalence of heart disease (>8%) such as the cohort aged > or =65 years (men, area under ROC curve = 0.88; cost

Effort angina in a middle-aged woman with abnormally high levels of serum high-density lipoprotein cholesterol: a case of cholesteryl-ester transfer protein deficiency.

A 54-year-old female was admitted to hospital complaining of oppressive anterior chest pain during exercise. Treadmill exercise ECG testing showed significant ischemic ECG changes, and electron-beam computed tomography demonstrated patchy calcifications in the coronary artery. Coronary angiography revealed a significant stenotic lesion of the right coronary artery. On routine investigations, no classical coronary risk factors were found, although a very high concentration (209 mg/dl) of high-density lipoprotein cholesterol (HDL-C) was detected. The serum concentration of cholesteryl-ester transfer protein (CETP), which plays a central role in the reverse cholesterol transport system, was measured and found to be less than the measurable minimum. The patient showed one of the typical genetic CETP mutations (intone 14 splicing defect), and her lipid profile was improved by administration of probucol for 3 months. A very high concentration of HDL-C with a defect of CETP activity may be a specific biochemical indicator pointing to an increased risk of premature coronary artery disease, and the lipid profile can be improved by use of lipid-lowering drugs.

Nitric oxide plays an insignificant role in direct vasodilator effects of calcium channel blockers in healthy humans.

Several experimental studies have suggested that the vasodilatory effects of calcium channel blockers (CCBs) are due in part to an endothelium-dependent mechanism. However, it remains unknown whether CCBs directly augment liberation of endothelium-derived dilator substances such as nitric oxide (NO) in the human vasculature. The aim of this study was to examine whether CCBs of several kinds directly increase the bioavailability of NO in forearm resistance vessels. Twenty-four healthy men (mean age 30 +/- 2 years) were randomly assigned to three study groups (n = 8 in each), and each group was assigned one of three first-generation CCBs (nifedipine, nicardipine, diltiazem). Subdepressor doses of CCBs [4, 8, 16, 24, and 36 (diltiazem only) nmol/min; for 2 min in each dose] were infused intra-arterially, and forearm blood flow (FBF) was determined plethysmographically. After control FBF responses to CCBs had been measured, a NO synthase inhibitor (N(G)-monomethyl-L-arginine: L-NMMA) was infused intra-arterially, and the FBF response to CCBs was again determined. Further, as a positive control for NO stimulation, acetylcholine (ACh) was also examined before and after L-NMMA in each group. Systemic blood pressure and heart rate did not change significantly during the study protocol. The FBF responses to these CCBs did not differ before and after NO synthase inhibition by L-NMMA (FBF at maximum doses: nifedipine, 8.0 +/- 0.8 vs. 7.3 +/- 0.7; nicardipine, 7.3 +/- 1.5 vs. 6.5 +/- 1.3; diltiazem, 5.7 +/- 0.7 vs. 4.2 +/- 0.7 ml/min per 100 ml: all not significant), although FBF responses to ACh were significantly reduced by L-NMMA. In conclusion, direct NO liberation does not make a significant contribution to the vasodilation associated with first-generation CCBs in healthy human resistance vessels.

Reduced vascular compliance is associated with impaired endothelium-dependent dilatation in the brachial artery of patients with congestive heart failure.

BACKGROUND: Alterations in elastic properties and vascular structure of conduit vessels are important detrimental factors contributing to increased cardiac load and reduced tissue perfusion in patients with congestive heart failure (CHF). It has been demonstrated that endothelial function in the peripheral vasculature is impaired in this disorder, which may induce abnormal vascular elastic properties and remodeling. However, it remains unknown whether changes in vascular structure or mechanical properties are related to endothelial dysfunction in conduit arteries of patients with CHF. METHODS AND RESULTS: Twenty-five CHF patients with nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial artery diameter, intima-media thickness (IMT), and vascular stiffness as represented by distensibility and compliance were determined using a high-frequency linear transducer attached to a high-quality ultrasound system. In addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial artery. Brachial arterial diameter was similar between CHF and controls; however, IMT and wall/lumen ratio were significantly greater in CHF patients than in controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus 15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa, P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG were significantly reduced in CHF (both P<.001). Although stiffness parameters in CHF were not significantly correlated with vascular structure (ie, IMT, wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure), elastic parameters were significantly correlated with FMD (distensibility; r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION: The present study found that, in limb muscle conduit artery in patients with CHF, there are hypertrophic remodeling and endothelial dysfunction-associated alterations in vascular wall elastic properties.