Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis.

Rationale: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. Objective: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. Methods and Results: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors-matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. Conclusions: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.

The effect of hypohydration on endothelial function in young healthy adults.

PURPOSE: Hypohydration has been suggested as a predisposing factor for several pathologies including cardiovascular diseases (CVD). While CVD are the leading cause of death worldwide, no study has investigated whether acute hypohydration affects endothelial function and cardiovascular function. METHODS: Ten young, healthy males participated in this crossover study (age: 24.3 ± 2.3 year; weight: 80.8 ± 5.3 kg; BMI: 24.3 ± 0.4 kg m-2). Each subject completed two measurements of endothelial function by flow-mediated dilation (FMD) in euhydrated and hypohydrated state separated by 24 h. Following baseline assessment of hydration status and FMD, the subjects completed 100 min of low-intensity intermittent walking exercise to achieve hypohydration of -2 % of individual body mass. For the rest of the day, a standardized, low water content diet was provided. The following morning, hydration markers and endothelial function were recorded. RESULTS: Hypohydration by -1.9 ± 0.1 % of body mass resulted in decreased plasma volume by -3.5 ± 1.8 % and increased plasma osmolality by 9 ± 2 mmol kg-1 (P < 0.001). FMD as a response to hypohydration decreased by -26.8 ± 3.9 % (P < 0.05). CONCLUSION: The data suggested that a small degree of hypohydration induced by moderate exercise and fluid restriction significantly impaired endothelial function.

Circulating levels of TNF-like cytokine 1A correlate with reflected waves and atherosclerosis extent and may predict cardiac death in patients with stable coronary artery disease.

BACKGROUND: TNF-like cytokine 1A (TL1A)-mediated interactions are involved in atheromatic plaque formation. In stable coronary artery disease (CAD) we examined whether circulating TL1A levels correlate with coronary and/or peripheral atherosclerosis extent and predict future cardiovascular events. METHODS: In this cross-sectional study, peripheral vascular studies and TL1A serum measurements were performed in 122 consecutive patients with angiographically confirmed CAD who were followed for a median of 41.9 months. TL1A levels were compared against controls (n = 63) and 20 patients with acute coronary syndrome (ACS). RESULTS: TL1A was higher in ACS than the 2 other groups (p < 0.001). In stable CAD, after adjustment for traditional risk factors independent positive correlations between TL1A serum levels and reflected waves (p = 0.049), and carotid atheromatic plaque score (p = 0.049) were evident. In stable patients with a history of ACS, TL1A levels correlated with worse endothelial function (p = 0.006), extent of CAD assessed by Gensini score (p = 0.042), and cardiac mortality (p = 0.051). CONCLUSIONS: This pilot study suggests that serum TL1A measurements are of clinical value in CAD. Studies on the pathogenetic role of TL1A in atherosclerosis and its sequelae are warranted.

The effect of hormone therapy on biochemical and ultrasound parameters associated with atherosclerosis in 46,XY DSD individuals with female phenotype.

The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2 mg 17ß-estradiol/1 mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC), LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow-mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT raised HDL (35.4 mg/dl versus 40.1 mg/dl, p = 0.019) while lowering TG (166 mg/dl versus 109 mg/dl, p = 0.026) and AIP (0.24 versus 0.04, p = 0.007). No changes were noted in TC and LDL (215.7 mg/dl versus 192.25 mg/dl and 87.46 mg/dl versus 76.35 mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05 ng/ml versus 2.20 ng/ml, p = 0.002) and E-selectin (73.98 ng/ml versus 56.73 ng/ml, p = 0.004). No change was observed in Thrombomodulin and vWf (11.76 ng/ml versus 13.90 ng/ml and 80.75% versus 79.55%, respectively). FMD improved significantly (5.4% versus 8.15%, p = 0.003), while only carotid bulb IMT decreased significantly (0.65 mm versus 0.60 mm, p = 0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.

Prediction of long-term outcomes by arterial stiffness and pressure wave reflections in patients with acute stroke: the Athens Stroke Registry.

BACKGROUND AND PURPOSE: Stroke patients' management might be improved by addressing the role of aortic stiffness (carotid-femoral pulse wave velocity: cfPWV) and pressure wave reflections (PWRs, augmentation index: AIx) in their pathogenesis and outcome. We tested the hypothesis that cfPWV and AIx, separately and combined, predict long-term outcomes [all-cause mortality, incidence of cardiovascular events, stroke recurrence and disability defined by modified Ranking Scale (mRS) ≥3] in patients with acute stroke, using data from the 'Athens Stroke Registry'. METHODS: Data from 552 patients (70% men, age: 66.1 ±â€Š10.4 years, 13.4% deaths from any cause, 21.2% cardiovascular events, 14.1% stroke recurrences and 20.1% poor mRS, mean follow-up 68.4 ±â€Š41.4 months) were analyzed. RESULTS: The main findings were that: high aortic stiffness (cfPWV > 13 m/s) alone is an independent predictor of all-cause mortality and cardiovascular (CV) events, but not of stroke recurrence and poor functional outcome; evaluated separately from aortic stiffness, neither low nor high PWRs have any prognostic value; even after multiple adjustments, patients with both high aortic stiffness (cfPWV > 13 m/s) and low PWRs (Aix < 22%) have almost two-fold higher hazard ratio, not only for all-cause mortality and CV events but also for stroke recurrence and poor functional outcome. CONCLUSIONS: The present study provides evidence about the role of aortic stiffness, PWRs and their combined incremental value in the long-term survival, morbidity, and functional disability after acute stroke.

Atherosclerosis in rheumatoid arthritis versus diabetes: a comparative study.

OBJECTIVE: The extent to which atherosclerosis is accelerated in chronic inflammatory diseases is not established. We compared preclinical atherosclerosis in rheumatoid arthritis with diabetes mellitus, a known coronary heart disease equivalent. METHODS AND RESULTS: Endothelial function, arterial stiffness, carotid intima-media thickness, and analysis of atheromatous plaques were examined in 84 rheumatoid arthritis patients without cardiovascular disease versus healthy controls matched for age, sex, and traditional cardiovascular disease risk factors, as well as in 48 diabetes patients matched for age, sex, and disease duration with 48 rheumatoid arthritis patients. Rheumatoid arthritis duration associated with arterial stiffening, whereas disease activity associated with carotid plaque vulnerability. All markers of preclinical atherosclerosis were significantly worse in rheumatoid arthritis compared to controls, whereas they did not differ in comparison to diabetes despite a worse cardiovascular risk factor profile in diabetics. Both diseases were associated independently with increased intima-media thickness; rheumatoid arthritis, but not diabetes, was independently associated with endothelial dysfunction. CONCLUSIONS: Preclinical atherosclerosis appears to be of equal frequency and severity in rheumatoid arthritis and diabetes of similar duration with differential impact of traditional risk factors and systemic inflammation. Cardiovascular disease risk factors in rheumatoid arthritis may need to be targeted as aggressively as in diabetes.

Impact of prehypertension on common carotid artery intima-media thickness and left ventricular mass.

BACKGROUND AND PURPOSE: Prehypertension has been recently introduced by JNC 7 as a new blood pressure (BP) category, associated with increased target-organ damage. Subclinical atherosclerosis by means of common artery intima-media thickness (CCA-IMT) has been incompletely investigated in prehypertensive patients. The aim of our study was to assess the extent of CCA-IMT and left ventricular mass (LVM) in prehypertensive adults in comparison to normotensive and untreated hypertensive subjects. METHODS: From a total of 5221 consecutive patients screened to our Hypertension Unit we selected 896 consecutive individuals according to prespecified inclusion criteria, who underwent 24-hour ambulatory BP monitoring, carotid artery ultrasonographic, and echocardiographic measurements. Patients who received antihypertensive treatment during the BP monitoring were excluded. According to the office BP levels, patients were divided into 3 subgroups: normotensives (office BP <120/80 mm Hg), prehypertensives (120/80 mm Hgor=140/90 mm Hg). Statistical analyses were performed by means of 1-way ANOVA, chi(2) test, and ANCOVA. RESULTS: According to the office BP levels, the distribution of the study population was: normotensives (14.4%), prehypertensives (23.7%), and hypertensives (61.9%). Prehypertensive patients had higher CCA-IMT (P=0.038) and LVM (P=0.030) values than normotensive subjects, even after adjustment for baseline characteristics. Greater CCA-IMT values were observed in hypertensive patients in comparison to prehypertensives (P=0.002). CONCLUSIONS: Prehypertensive patients had higher CCA-IMT and LVM than their normotensive counterparts. Prehypertension status is cross-sectionally associated with subclinical atherosclerosis and target-organ damage.

Treatment with granulocyte colony stimulating factor is associated with improvement in endothelial function.

PRIMARY OBJECTIVE: Granulocyte-colony stimulating factor (G-CSF) is used for the mobilization of bone marrow and endothelial progenitor cells, though G-CSF-induced inflammation may cause endothelial dysfunction. We examined the effects of G-CSF on endothelium, C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha) and anti-inflammatory cytokines namely interleukin 10 (IL-10). RESEARCH DESIGN: We studied 60 women with breast cancer, who were randomized to either subcutaneous G-CSF (5 microg/kg), o.d. for 5 days after adjuvant chemotherapy (n = 40) or placebo (n = 20). EXPERIMENTAL INTERVENTIONS: We measured flow-mediated dilatation (FMD%) of the brachial artery by ultrasonography, CRP, TNF-alpha, IL-10 and the ratio TNF-alpha/ IL-10 blood levels before, 2-h and 5-days after the G-CSF or placebo treatment. MAIN OUTCOMES AND RESULTS: There was a greater increase of FMD, IL-10 and reduction of TNF-alpha/ IL-10, 2 h and 5 days after the G-CSF treatment compared to placebo. Although, CRP and TNF-alpha were higher, TNF-alpha/IL-10 was lower at the end of G-CSF treatment compared to placebo. Improvement of FMD was related to changes of IL-10 and TNF-alpha/IL-10. CONCLUSIONS: Treatment with G-CSF improves endothelial function in vivo, possibly by shifting the balance between the pro- and anti-inflammatory cytokines.

Circulating levels of TNF-like cytokine 1A (TL1A) and its decoy receptor 3 (DcR3) in rheumatoid arthritis.

TL1A is a novel TNF-like cytokine, which provides co-stimulatory and Th1-polarizing signals to activated lymphocytes, via binding to death-domain receptor 3 (DR3). These functions are inhibited when TL1A associates to decoy receptor 3 (DcR3). We investigated the serum expression of TL1A and DcR3 in 81 patients with RA and 51 healthy controls. TL1A concentrations were elevated in patients by 5-fold (P<0.00001). This increase was more prominent in RFactor-positive patients and correlated with clinical activity in this subgroup. DcR3 was detected more frequently and in significantly higher values in RA-derived sera, correlated strongly with TL1A, and was present in inflammatory synovial fluid. Severe RA stage was associated with highly elevated TL1A and DcR3 serum levels. Treatment with an anti-TNF agent significantly decreased TL1A serum levels. We conclude that TL1A may serve as an inflammatory marker in RA. Interactions between TL1A and its receptors may be important in the pathogenesis of RA.

Acute combined effects of olive oil and wine on pressure wave reflections: another beneficial influence of the Mediterranean diet antioxidants?

OBJECTIVES: Combined consumption of olive oil and wine is common in the Mediterranean diet, but there are no data concerning their synergistic haemodynamic response. We sought to determine the combined postprandial effects of wine and olive oil on wave reflections and central haemodynamics. METHODS: Fifteen healthy subjects consumed four standard meals on different days, containing 50 g of olive oil and 250 ml of wine, in a randomized cross-over study design. Two types of wine [red (R) and white (W)] and two types of olive oil [green (G) and refined (O) (rich and poor in antioxidants, respectively)] were used in all possible combinations (RO, RG, WO and WG). Applanation tonometry and aortic pulse wave analysis were performed when fasting and 1, 2 and 3 h postprandially. A second group of 15 healthy individuals matched for age, gender and body mass index served as the control group. RESULTS: All meals decreased AIx (RO and RG, P < 0.001; WO, P = 0.007; and WG, P = 0.039). The AIx reduction after RG, RO, WO and WG was significantly different from the respective AIx response of the control group. No difference was observed in the reduction of AIx between sessions, but a significantly earlier peak decrease in AIx, as well as a more prolonged decreasing effect, was observed after RG and RO consumption compared to WO and WG. Central systolic and diastolic pressures were diminished after all four combinations of wine and olive oil (P < 0.05). CONCLUSIONS: Combined consumption of wine and olive oil provided beneficial postprandial effects on haemodynamics. These findings reveal an additional favourable effect of components of the Mediterranean diet on haemodynamics in the postprandial state.

Target organ damage in "white coat hypertension" and "masked hypertension".

BACKGROUND: In this study we investigated (i) the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in patients who had never been treated earlier with antihypertensive medication, and (ii) the association of these conditions with target organ damage. METHODS: A total of 1,535 consecutive patients underwent office blood pressure (BP) measurements, 24-h ambulatory BP monitoring (ABPM), echocardiography, and ultrasonography of the carotid arteries. Subjects who showed normotension or hypertension on the basis of both office and ambulatory BP (ABP) measurement were characterized as having confirmed normotension or confirmed hypertension, respectively. WCH was defined as office hypertension with ambulatory normotension, and MH as office normotension with ambulatory hypertension. RESULTS: WCH was found in 17.9% and MH in 14.5% of the subjects. The prevalence of WCH was significantly higher in subjects with obesity, while the prevalence of MH was significantly higher in normal-weight subjects. The confirmed hypertensive subjects as well as the masked hypertensive subjects had significantly higher left ventricular mass (LVM) (corrected for body surface area) and carotid intima media thickness (cIMT) than the confirmed normotensive subjects did (108.9 +/- 30.6, 107.1 +/- 29.1 vs. 101.4 +/- 29.9 g/m(2) and 0.68 +/- 0.16, 0.68 +/- 0.21 vs. 0.63 +/- 0.15 mm, respectively, P < 0.005). White coat hypertensive subjects did not have a significantly higher LVM index than confirmed normotensive subjects (101.5 +/- 25.9 vs. 101.4 +/- 29.9 g/m(2)); they tended to have higher cIMT than the confirmed normotensive subjects, but the difference was not statistically significant (0.67 +/- 0.15 vs. 0.63 +/- 0.15 mm). CONCLUSIONS: WCH and MH are common conditions in patients who visit hypertension outpatient clinics. Confirmed hypertension and MH are accompanied by increased LVM index and cIMT, even after adjusting for other risk factors.

Heartscore calculated in individuals younger than 40 years is related to vascular markers of early atherosclerosis.

BACKGROUND: Heartscore is not well validated for individuals less than 40 years of age. In the latest guidelines a relative risk chart is provided with the proposal to be used for young adults aged less than 60 years instead of projecting risk at the age of 60 years. Moreover, coronary artery disease is insidiously manifested in younger patients. DESIGN: Cross-sectional study. METHODS: Two hundred and two young Greeks of age less than 40 years and 232 middle-aged adults aged 40-60 years without clinically overt cardiovascular disease or diabetes were consecutively recruited. Flow-mediated dilatation of the brachial artery, carotid, and femoral intima media thickness (IMT), carotid-radial and carotid-femoral pulse wave velocity (PWV) were measured in all individuals in one session. The European Society of Cardiology online Heartscore calculator was used for mortality risk (MR) 60 and Systematic Coronary Risk Evaluation risk charts for relative risk (RR) computation. RESULTS: MR60 in the younger significantly correlated with all measured vascular markers whereas RR significantly correlated with carotid IMT. By multivariate regression analysis, MR60 was a stronger identifier than RR for PWV, mean carotid and femoral IMT in both groups. Young adults (<40 years) with a high MR60 (>5%) had significantly higher carotid-radial PWV, carotid and femoral IMT whereas those with a high RR (>3rd tertile) had significantly higher carotid IMT. CONCLUSION: MR60 was a stronger identifier of most of the measured markers of early atherosclerosis as compared with RR. These data support Heartscore as a prognostic tool in terms of primary prevention for participants younger than 40 years old.

Postprandial improvement of endothelial function by red wine and olive oil antioxidants: a synergistic effect of components of the Mediterranean diet.

OBJECTIVE: Consumption of olive oil may cause postprandial impairment of endothelial function, while acute ingestion of red wine seems to improve it. The purpose of the present study was to investigate the combined postprandial effects of two essential components of the Mediterranean diet, red wine and olive oil, on endothelial function. METHODS: Fifteen healthy subjects were enrolled in the study, which was comprised of 4 study days. Subjects were asked to consume a standard meal at each study day containing 50 gr of olive oil and 250 ml of wine. Two types of wine (red and white; rich and poor in antioxidants respectively) and two types of olive oil (green and refined; rich and poor in antioxidants respectively) were used in a 2*2 design. Endothelium dependent, flow mediated dilatation (FMD) was measured with a B-Mode ultrasound device at fast and 1, 2 and 3 hours postprandially. RESULTS: Combined consumption of red wine and green olive oil (both rich in antioxidants) improved FMD postprandially (p = 0.002, ANOVA for repeated measures), which remained significant 1 hour (p = 0.002) and 2 hours (0.037) following the meal compared to fasting levels. No other combination of wine and olive oil caused any significant alteration on FMD. CONCLUSION: Acute consumption of both red wine and green olive oil, rich in antioxidants, led to an improvement in the postprandial endothelial function in healthy subjects. These findings provide an additional favorable effect of components of the Mediterranean diet and of their antioxidant substances on endothelial function, at the postprandial state.

Correlations of sialic acid with markers of inflammation, atherosclerosis and cardiovascular events in hemodialysis patients.

BACKGROUND: Serum total sialic acid (S-TSA) is associated with atherosclerotic process in general population. The aim of our study was to evaluate possible correlations of S-TSA with markers of inflammation and atherosclerosis in hemodialysis (HD) patients. METHODS: We involved 53 asymptomatic, nondiabetic HD patients and 28 healthy controls. Atherosclerosis was evaluated by carotid ultrasonography, estimating intima media wall thickness and wall to lumen ratio bilaterally. To confirm our findings, we performed a 32-month cohort study, during which cardiovascular (CV) events were analyzed in relation to S-TSA concentration. RESULTS: HD patients had higher S-TSA compared to controls (adjusted OR: 1.04, p = 0.026). In HD patients, S-TSA independently correlated with hs-CRP (p < 0.0001), lipoprotein(a) (p = 0.02), intima media wall thickness (p = 0.023) and wall to lumen ratio (p = 0.028). Increased S-TSA concentration was associated with more CV events (p = 0.03). CONCLUSIONS: Serum TSA seems to correlate with inflammation, accelerated atherosclerosis and CV events in nondiabetic HD patients, but more studies need to confirm our findings.

Central blood pressures: do we need them in the management of cardiovascular disease? Is it a feasible therapeutic target?

It is well established that in young and healthy individuals central (aortic or carotid) systolic and pulse pressures are different from peripheral (brachial) corresponding pressures as a consequence of progressive changes in arterial stiffness and pressure wave reflections along the arterial tree. There is evidence indicating that in interventions with pharmaceutical and non-pharmaceutical agents, central pressures are subjected to greater changes than peripheral pressures, and they are more closely related to the pathophysiology of end-organ damage or cardiovascular risk. Therefore central blood pressures may be of higher clinical importance than peripheral pressures. The present review aims to provide an insight into the (patho)physiology of central blood pressures, to present the most accurate techniques for their estimation, and to discuss the available experimental and epidemiological data that support the emerging need for the evaluation of central blood pressures in clinical practice.

Hour-to-hour and week-to-week variability and reproducibility of wave reflection indices derived by aortic pulse wave analysis: implications for studies with repeated measurements.

BACKGROUND: Wave reflections are implicated increasingly in clinical research. AIMS: The purpose of the present study was to investigate whether wave reflection indices are reproducible when measured repeatedly (more than twice) at longer time intervals, namely hour-to-hour and week-to-week, in healthy subjects; something that has not yet been examined. METHODS: Bland-Altman plots, the interclass correlation coefficients (ICC) and coefficient of variation were used for this purpose. Two series, with measurements repeated in triplicate, were performed in 22 healthy subjects: the first at intervals of 1 h and the second at 1-week time intervals. Augmentation index (AIx), heart rate-corrected AIx (AI@75) and arrival time of reflected waves at the central aorta (tr) were calculated by aortic pulse wave analysis. RESULTS: AIx and AI@75 presented very good to excellent reproducibility (ICC = 0.86) for hour-to-hour repeated measurements, while tr was also highly reproducible (ICC = 0.79). AIx, AI@75 and tr were substantially reproducible when measured repeatedly with 1-week intervals, providing ICCs greater than 0.70. Bland-Altman plots confirmed these results, indicating that more than 90% of AIx, AI@75 and tr measurements fell within two standard deviations of the mean difference. CONCLUSIONS: Wave reflections are substantially reproducible even when measurements repeated in triplicate are performed at longer time intervals (hours and weeks). A quantifiable amount of variation was reported, which should be taken carefully into consideration in interventional studies with repeated measurements and in observational studies investigating differences or correlations of these indices.

High anticipatory stress plasma cortisol levels and sensitivity to glucocorticoids predict severity of coronary artery disease in subjects undergoing coronary angiography.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and/or increased sensitivity of peripheral tissues to glucocorticoids may be associated with the dysmetabolic syndrome and its cardiovascular sequelae. In this prospective pilot clinical study, we examined possible associations between HPA axis activity and severity of cardiovascular disease. We measured morning serum cortisol and intima media thickness (IMT) of carotid and femoral arteries in 105 subjects before undergoing coronary angiography for suspected coronary artery disease (CAD). In a randomly selected 46 of these subjects, we obtained late afternoon and morning cortisol levels (after ultralow-dose dexamethasone [0.25 mg] treatment) and determined their genotype for the Bcl1 polymorphism of the glucocorticoid receptor gene, which has been associated with increased sensitivity to glucocorticoids. There was significant association between morning preangiography cortisol levels and the number of vessels with severe stenosis in the angiography, independently of age or sex (P = .002), and a trend for a positive correlation between morning cortisol and the IMT of the femoral artery (P = .057). Bcl1 G allele homozygotes had a significantly higher carotid IMT (P = .005) and a nonsignificant tendency for higher waist-hip ratio (P = .059). Hyperactivity of the HPA axis in anticipation of a stressful procedure, such as angiography, may be an index of CAD severity. Chronic HPA axis hyperreactivity combined with tissue hypersensitivity to glucocorticoids may contribute to more severe atherosclerosis and CAD.

Ability of ambulatory blood pressure monitoring and myocardial/carotid ultrasound to predict the location and the severity of coronary artery lesions in normotensive patients: a clinical study.

Pulse pressure has been recognized as a marker of cardiovascular disease in normotensives. Moreover, internal carotid artery intima-media thickness (IMT) has been proposed to reflect coronary artery lesions. The aim of the present study was to evaluate the predictive value of other parameters derived from ambulatory blood pressure monitoring (ABPM), myocardial ultrasound, and carotid ultrasound to predict the location and the severity of coronary artery disease in normotensives. One hundred and thirteen patients with suspected coronary artery disease underwent coronary angiography, 24-h ABPM and myocardial/carotid ultrasound. Multivariate analysis was applied and equations were extrapolated based on independent variables derived from ABPM and ultrasound. The Gensini score was independently correlated with male gender, pulse pressure, average heart rate for both 24-h (p=0.001) and night (p=0.006) values, as well as percentage of high systolic blood pressure (BP), average diastolic BP, average mean BP, and heart rate concerning daily mesurements (p=0.001). Moreover, the Gensini score was independently correlated with end-systolic volume, posterior wall thickness during systole and intraventricular septum thickness during diastole, along with male gender and age (p=0.001), as well as mean internal and right common carotid artery IMT (p=0.002). Similar mathematical formulas have been calculated separately for the coronary arteries and their main branches. In conclusion, the location and the severity of coronary disease can be effectively evaluated by ABPM and myocardial/carotid ultrasound in normotensives. This approach could be useful for determining atypical patients at risk and/or for treating patients with suspected coronary disease who refuse coronary angiography.

Differential associations of systolic and diastolic time rate of blood pressure variation with carotid atherosclerosis and plaque echogenicity.

In the current study, the authors sought to assess whether the time rate of systolic and diastolic blood pressure variation is associated with advanced subclinical stages of carotid atherosclerosis and plaque echogenicity assessed by gray scale median. The authors recruited 237 consecutive patients with normotension and hypertension who underwent 24-hour ambulatory blood pressure monitoring and carotid artery ultrasonography. There was an independent association between low 24-hour systolic time rate and increased echogenicity of carotid plaques (adjusted odds ratio for highest vs lower tertiles of gray scale median, 0.470; 95% confidence interval, 0.245-0.902 [P = .023]). Moreover, increased nighttime diastolic time rate independently correlated with the presence (adjusted odds ratio, 1.328; P = .015) and number of carotid plaques (adjusted odds ratio, 1.410; P = .003). These results indicate differential associations of the systolic and diastolic components of time rate of blood pressure variation with the presence, extent, and composition of carotid plaques and suggest that when blood pressure variation is assessed, both components should be considered.

Common carotid artery intima-media thickness and the risk of stroke recurrence.

BACKGROUND AND PURPOSE: Increased common carotid artery intima-media thickness (CCA-IMT) has been associated with an increased risk of myocardial infarction and stroke. We investigated the relationship between CCA-IMT and recurrent stroke in a cohort of ischemic stroke patients. METHODS: High-resolution B-mode ultrasonographic measurements of the CCA-IMT were performed in a consecutive series of 238 patients hospitalized in our institution with first-ever ischemic stroke. Stroke risk factors and secondary prevention therapies were documented. Patients were followed-up prospectively and the outcome event of interest was recurrent stroke. RESULTS: During a mean follow-up period of 28.9 months (range: 6 to 60 months), 27 recurrent strokes were documented. Patients who experienced recurrent cerebrovascular events had significantly (P=0.005) higher CCA-IMT values (1.01 mm, 95% CI:0.92 to 1.11 mm) than subjects who were free of stroke recurrence (0.88 mm, 95% CI:0.85 to 0.91 mm). After adjustment for baseline characteristics, risk factors and stroke subtypes and secondary prevention therapies increasing CCA-IMT was found to be an independent predictor of stroke recurrence. For each increment of 0.1 mm in CCA-IMT the probability of experiencing recurrent stroke increased by 18.0% (95% CI:2.0% to 36.0%, P=0.027). CONCLUSIONS: Increased CCA-IMT values are associated with a higher risk of long-term stroke recurrence.