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.

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.

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.

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.

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.

Genetic variations of the endothelial nitric oxide synthase gene are related to increased levels of C-reactive protein and macrophage-colony stimulating-factor in patients with coronary artery disease.

It was the objective of this study to investigate the relation between nitric oxide synthase (NOS3) gene polymorphisms, vascular inflammation, endothelial function, and atherosclerosis. We examined the effects of a variable nucleotide tandem repeats (VNTR) in intron 4, G894T in exon 7 and T-786C at the promoter region of NOS3 on i) C-reactive protein (CRP) and macrophage-colony stimulating-factor (MCSF), and ii) augmentation index (AI) measured by pulse-wave analysis , flow-mediated dilation (FMD) of the brachial artery, intima-media thickness (IMT) of the carotid and femoral artery using ultrasonography and ankle-brachial index (ABI) in 122 patients with chronic coronary artery disease (CAD) who underwent coronary angiography. MCSF and CRP were increased in patients withT-786C (77/122) or VNTR (40/122) allele compared to those without (F = 10.8, p = 0.002 and F = 3.8, p = 0.04 for T-786C and F = 3.65, p = 0.04 and F = 3.2 p = 0.049 forVNTR), even after adjustment for traditional risk factors and medication. Patients with combination of VNTR and T-786C (31/122) had higher MCSF or CRP than patients with one or none of these alleles (p < 0.05). Among patients with T-786C, those with MCSF>262 pg/ml or CRP>3.2 mg/l (n = 33/77) had a higher femoral and carotid IMT and number of plaques in the peripheral arteries than those with lower values of these inflammatory indices (p < 0.05). Patients with MCSF >262 pg/ml had also lower FMD and higher Gensini score than those with lower MCSF (p < 0.05). The intron 4-VNTR and T-786C mutation of NOS3 gene enhance the inflammatory process in patients with chronic CAD.

Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation.

Coronary endothelial vasodilator dysfunction is associated with increased cardiac events; the close relation between coronary vasomotor dysfunction and brachial artery vasoreactivity has been previously described. This study assessed the prognostic value of noninvasively assessed brachial artery vasoreactivity in survivors of acute coronary syndromes without ST-segment elevation. We examined 98 men (63.1 +/- 10.8 years) who were referred to our hospital for acute coronary syndromes without ST-segment elevation. Brachial artery endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitrate-mediated dilation were examined in all patients using high-resolution echocardiographic Doppler ultrasound within 24 hours of admission. Plasma malondialdehyde, a marker of oxidative stress, and left ventricular ejection fraction were also assessed. Twenty-seven patients underwent coronary revascularization. Patients were followed for 24.8 +/- 5.9 months. Cardiovascular death, myocardial infarction, stroke, and unstable angina were designated as cardiovascular events (CEs). Twenty CEs were recorded. Kaplan-Meyer analysis showed that patients with FMD <1.9% (tertile 1 of FMD values) were more likely to have CEs than those with FMD >1.9% (log rank 5.29, p = 0.021). Multivariate Cox regression analysis showed that FMD <1.9% predicted CEs with an adjusted hazard ratio of 3.035 (95% confidence interval 1.148 to 8.023, p = 0.025) after adjustment for age, risk factors, troponin T, ejection fraction, revascularization procedures, number of diseased vessels, and medication. In conclusion, endothelium-dependent dilation of the brachial artery is a strong independent predictor of adverse outcome in survivors of acute coronary syndromes without ST-segment elevation.

Circadian variation of arterial pressure wave reflections.

BACKGROUND: Various factors are implicated in the circadian pattern of cardiovascular vulnerability. The exact mechanisms involved in the peak incidence of cardiovascular events occurring during the early morning hours after awaking are not completely known. The purpose of our study was to investigate the circadian variation of timing and intensity of wave reflections in healthy individuals and to test the hypothesis that significant changes occur during the day. METHODS: Thirteen healthy non-smokers (seven women and six men, mean age 40.7 +/- 16.5 years) were examined. Aortic pulse wave analysis was performed to estimate surrogates of wave reflections intensity (augmentation index [AIx]) and timing. Twelve measurements separated by 1-h intervals were performed from 8 am to 7 pm each study day. RESULTS: Analysis of variance for repeated measures indicated significant changes during the 12-h period for heart rate corrected AIx (P = .033) and heart rate (P = .035). The AIx was maximal at 8 am within 1-h after awaking (17% +/- 3.6%); it was gradually diminished until 3 pm (9% +/- 4.1%) and again increased to a second (albeit lower) peak value during the late afternoon (7 pm). CONCLUSIONS: It is possible that the increased intensity of reflected waves occurring during the early morning in combination with the rising trend of blood pressure and heart rate at the same time results in an aggravated left ventricular afterload and an increase in myocardial oxygen demand. The morning-related enhancement of wave reflections may have potential implications for the increased risk for cardiovascular events during the early morning, which remains to be clarified.

Transmission of calibration errors (input) by generalized transfer functions to the aortic pressures (output) at different hemodynamic states.

BACKGROUND: Aortic pressure waveforms are calculated non-invasively by applying generalized transfer functions (GTF) to tonometric radial pressure waveforms. Input errors mainly during acquisition and calibration of tonometric pressures are "transferred" to aortic pressure calculation. The present study aimed to quantify the proportion of specific input errors which is "transferred" by the GTFs in a wide range of hemodynamic conditions and for different error combinations in brachial systolic (SBP) and diastolic (DBP) blood pressure measurements. METHODS: Aortic pulse wave analysis was performed in 103 subjects (52 normotensive and 51 untreated hypertensive) by the SphygmoCor System. Each pressure waveform was initially calibrated by sphygmomanometrical brachial pressures. Isolated, parallel and reverse errors in brachial SBP/DBP from -10 to +10 mmHg were simulated, by recalibration of the recorded radial pressure waveforms, inducing specific "errors" of GTF-input values. For every recalculated aortic SBP and DBP, the difference from the initial estimated value was considered to represent the "transferred error" to the aortic pressure estimation. RESULTS: Parallel errors by +/-5 mmHg in both SBP and DBP resulted to an identical change in GTF-derived aortic pressures, as expected. When an overestimation in SBP by 5 mmHg and an underestimation in DBP by -5 mmHg occurred (reverse errors), almost 56% of this error (approximately 2.8 mmHg) was transferred. An isolated error in brachial SBP by +/-5 mmHg was transmitted by 76% ( approximately 3.8 mmHg) to GTF-derived aortic SBP. In subjects with mean blood pressure>117 mmHg or with heart rates<74 bpm, a greater percent of the calibration error was transferred to GTF-derived blood pressures. CONCLUSIONS: Input errors in brachial pressure values result in a quantifiable effect on transfer function output (aortic pressures). The percent of the "error transfer" by the GTFs depends on heart rate and BP levels, which should be taken into account when applying GTFs at populations with different hemodynamic conditions.

Carotid artery intima-media thickness could predict the presence of coronary artery lesions.

The purpose of the present study was to examine whether intima-media thickness (IMT) predicts the presence of the coronary artery lesions independent of other risk factors including clinic blood pressure (BP), parameters of 24-h ambulatory BP monitoring, body mass index, serum cholesterol, and glucose levels. The study population consisted of 390 consecutive subjects who had recently undergone coronary arteriography; 51 subjects with no measurable lesions in their coronary arteries (control group) and 339 subjects with coronary artery lesions (coronary artery disease [CAD] group). Mean IMT of the common carotid artery (MCCA) and internal carotid artery (MICA) were significantly higher in subjects with CAD compare control subjects (P < .0001). Carotid IMT could predict the presence of coronary artery lesions independently of clinic or ambulatory BP values, BMI, serum cholesterol, and glucose levels (P < .01). Carotid IMT predicted the presence of significant coronary artery lesions with cutoff values 0.85 and 0.80 for MICA and MCCA, respectively. The IMT could be a clinical useful test for the presence of significant coronary artery lesions.

Red wine acutely induces favorable effects on wave reflections and central pressures in coronary artery disease patients.

BACKGROUND: To investigate red wine's acute effects on aortic pressures and arterial stiffness in patients with coronary artery disease (CAD). METHODS: Fifteen patients with CAD were recruited in a double-blind, cross-over study, which was comprised of 2 study days. Each volunteer consumed either 250 mL of regular or 250 mL of dealcoholized red wine. Wave reflections, expressed as augmentation index (AIx), as well as central and peripheral blood pressures (BP) were assessed at fast and 30, 60, and 90 min postprandially. RESULTS: Both regular and dealcoholized red wine caused a significant decrease in AIx by 10.5% +/- 1.4% (P = .001) and 6.1% +/- 1.4% (P = .011), respectively, whereas no significant change was induced in mean BP and timing of wave reflections expressing pulse wave velocity. Peripheral systolic BPs remained unaltered in both beverages, whereas a significant decrease in peripheral and central diastolic BPs was observed after the dealcoholized red wine consumption (P = .03 and P = .035, respectively). Central systolic BP was decreased after the consumption of regular (-7.4 +/- 2.4 mm Hg, P = .05) and dealcoholized red wine (-5.4 +/- 2.7 mm Hg, P = .019). CONCLUSIONS: Both types of red wine provoked favorable acute effects on wave reflections and central systolic pressures, whereas no such effect was evident at the brachial artery. Therefore, these findings could be attributed mainly to red wine antioxidant substances, rendering it a possible means of at least acute attenuation of increased wave reflections, arterial stiffness, and central pressures in patients with coronary artery disease.

Arterial stiffness is increased in subjects with hypothyroidism.

BACKGROUND: The association between hypothyroidism and increased vascular resistance, arterial wall thickening and endothelial dysfunction is well recognized. The aim of the present study was to examine if hypothyroid subjects have increased arterial stiffness, a risk factor for cardiovascular morbidity and mortality. METHODS: Sixty-five subjects (59 females and 6 males) with normal thyroid function or hypothyroidism of varying degree were investigated by radial artery applanation tonometry and pulse wave analysis, for evaluation of arterial stiffness. RESULTS: Serum TSH values were positively correlated with central systolic blood pressure (r=0.258, p=0.037), central pulse pressure (r=0.316, p=0.010), augmentation pressure (r=0.299, p=0.015) and negatively with reflection time index (RTI), which indicates the pressure wave velocity (r=-0.311, p=0.012). Hypothyroid patients presented higher central systolic pressure and pulse pressure, higher augmentation pressure and lower RTI, indicating increased arterial stiffness in these subjects. RTI was independently related to age, central systolic pressure and TSH. Mild changes of arterial stiffness were observed even in subjects with TSH range 2.01-4.0 muU/ml suggesting that this group may have an early stage of mild thyroid failure. CONCLUSIONS: Hypothyroidism, even in the subclinical stage, is associated with changes in arterial stiffness. The observed abnormalities in arterial stiffness may have detrimental effects on left ventricular function and coronary perfusion in hypothyroid subjects.

Arterial stiffness assessed by pulse wave analysis in essential hypertension: relation to 24-h blood pressure profile.

BACKGROUND: Arterial stiffness is a risk factor for cardiovascular morbidity and mortality and appears to be increased in arterial hypertension. The purpose of the present study was to relate systemic arterial stiffness assessed by pulse wave analysis to variables of 24-h ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension. METHODS: Seventy-two subjects with untreated mild to moderate arterial hypertension underwent evaluation with 24-h ambulatory blood pressure monitoring. In the same subjects, applanation tonometry and pulse wave analysis was performed for evaluation of systemic arterial stiffness expressed as augmentation index and estimated aortic pulse wave velocity. RESULTS: Clinic systolic blood pressure, mean heart rate during 24-h blood pressure monitoring and height were independent predictors of augmentation index and estimated aortic pulse wave velocity. The 41 patients with blunted reduction in nighttime blood pressure (nondippers) showed higher mean systolic blood pressure (p=0.02), lower systolic and diastolic blood pressure variability (p<0.001), higher pulse pressure during 24-h monitoring (p=0.05) and higher estimated aortic pulse wave velocity (p=0.03), indicating stiffer arteries in this group. CONCLUSIONS: These results suggest that blood pressure change from day- to nighttime is an important determinant of arterial stiffness assessed by pulse wave analysis; this association could contribute to the higher cardiovascular risk in nondippers.

Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women.

BACKGROUND: Tamoxifen is a selective estrogen-receptor modulator shown to improve several cardiovascular risk factors in postmenopausal women with breast cancer. In animal studies tamoxifen inhibits the progression of atherosclerosis. Although the presence of a history with tamoxifen treatment is related to a lower intima-media thickness (IMT) of the common carotid artery, data from controlled follow-up studies are lacking to support this observation. METHODS: We examined 14 postmenopausal women with early stage breast cancer with indication for tamoxifen treatment (20 mg/d) and 13 healthy postmenopausal women. Flow-mediated dilatation (FMD) of the brachial artery, combined carotid IMT, and aortic pulse wave were measured before and 6 months after treatment in the tamoxifen group and at the same times in the control group. RESULTS: FMD and IMT were significantly increased and decreased, respectively, in the treatment group compared to the control group (FMD: +2.2% +/- 0.9% vs +0.085% +/- 1%, P =.012; IMT: -0.088 +/- 0.03 mm vs +0.04 +/- 0.03 mm, P =.018, mean +/- standard error of the mean, treatment vs control group). These differences remained significant even when adjusted for age, duration of menopause, and cardiovascular risk factors. Low-density lipoprotein cholesterol was also significantly reduced after tamoxifen treatment. CONCLUSIONS: Tamoxifen treatment slows the progression of atherosclerosis in postmenopausal women with breast cancer as assessed by changes in carotid IMT. An improvement in endothelial function and blood lipid profile may be the reason for this beneficial effect.

Oral L-arginine improves endothelial dysfunction in patients with essential hypertension.

BACKGROUND: L-Arginine is a nitric oxide precursor, which augments endothelium-dependent vasodilatation in hypercholesterolemic humans and animals. Endothelium-dependent vasodilation is attenuated in patients with hypertension; however the effects of oral L-arginine on endothelial function of the conduit arteries in patients with essential hypertension have not previously been investigated. METHODS: In a prospective randomized double blind trial, 35 patients with essential hypertension received either 6 g L-arginine (18 subjects) or placebo (17 subjects). Patients were examined for flow-mediated endothelium-dependent dilatation of the brachial artery before and 1.5 h after administration of L-arginine or placebo. At the end of the protocol the nitrate-induced, endothelium-independent vasodilatation was evaluated. RESULTS: Two groups of L-arginine and placebo were similar regarding age, sex, blood lipids, smoking, diabetes, coronary artery disease, body mass index, intima-media thickness of the common carotid artery, clinics blood pressure and baseline brachial artery parameters. Administration of L-arginine or placebo did not change significantly heart rate, blood pressure, baseline diameter, blood flow or reactive hyperemia. L-Arginine resulted in a significant improvement of flow-mediated dilatation (1.7+/-3.4 vs. 5.9+/-5.4%, P=0.008) while placebo did not significantly change this parameter (3.0+/-2.7 vs. 3.1+/-2.2%, P=ns). The effect of L-arginine on flow-mediated dilatation was significantly different from the effect of placebo (P=0.05). L-Arginine did not significantly influence nitrate-induced dilatation (16+/-6.9 vs. 17.7+/-6.7%, P=ns). CONCLUSIONS: Oral administration of L-arginine acutely improves endothelium-dependent, flow-mediated dilatation of the brachial artery in patients with essential hypertension. The long-term effects of L-arginine in these patients require further investigation.

Cardiac hypertrophy in hypertension: relation to 24-h blood pressure profile and arterial stiffness.

BACKGROUND: In subjects with essential hypertension peripheral blood pressure profile contributes to the pathogenesis of left ventricular hypertrophy. It is not known if central arterial pressure is superior to peripheral blood pressure profile for predicting left ventricular hypertrophy. In the present study 24-h blood pressure profile and central hemodynamics were examined to evaluate mechanical loading factors as determinants of cardiac hypertrophy in mild to moderate untreated essential hypertension. METHODS: Forty-eight untreated subjects with mild to moderate essential hypertension were examined by echocardiography for evaluation of left ventricular mass, 24-h ambulatory blood pressure monitoring (ABPM), and applanation tonometry of the radial artery with pulse wave analysis for evaluation of central hemodynamics. RESULTS: Left ventricular mass showed a statistically significant correlation with age, clinic systolic blood pressure, mean heart rate and heart rate variability during 24-h ABPM, augmentation pressure and index and central systolic blood pressure. In a multiple regression analysis including clinic systolic blood pressure, central systolic pressure, mean systolic pressure and pulse pressure during ambulatory monitoring as well as age, independent predictors of left ventricular mass were only age (P=0.006) and central systolic blood pressure (P=0.04). In conclusion, pulse wave analysis is a valuable method in predicting cardiac hypertrophy in untreated mild to moderate essential hypertension. Central systolic blood pressure should be taken into account for planning therapeutic strategies for prevention of left ventricular hypertrophy in hypertensive patients.

Ascorbic acid does not improve endothelium-dependent flow-mediated dilatation of the brachial artery in patients with Raynaud's phenomenon secondary to systemic sclerosis.

Previous studies have shown that patients with Raynaud's phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud's phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud's phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud's phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 +/- 2.2% to 2.2 +/- 2.5%, ns) or placebo administration (1.2 +/- 1.9% to 1.7 +/- 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 +/- 7.4% vs 17 +/- 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud's phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.

Oral administration of ascorbic acid attenuates endothelial dysfunction after short-term cigarette smoking.

Short-term cigarette smoking is associated with persistent endothelial dysfunction. Data on the reversibility of this effect with per os antioxidants after short-term smoking are lacking. This study examines the effect of orally administered ascorbic acid on cigarette smoking-induced endothelial dysfunction. In the present double-blind, randomized, crossover study, 19 healthy subjects (28.7 +/- 6.8 years, mean +/- SD) were examined by high-resolution ultrasonography of the brachial artery before and 0, 30, 60, 90, and 120 minutes after smoking a cigarette. Flow-mediated dilatation (FMD) was used as a method to examine endothelial function. Measurements were performed on two different days, 2 hours after oral administration of 2 g of ascorbic acid or placebo. FMD was similar for each subject between the two visits at baseline. FMD was significantly decreased after smoking with both placebo and ascorbic acid. However, there was a significant beneficial effect of ascorbic acid on the FMD change over time after smoking. After smoking, the FMD dropped to less than half of the baseline value. Thereafter in the placebo group, FMD increased to 70% of baseline value in 90 minutes, but in the ascorbic acid group the FMD increased to 70% of baseline value in 46 minutes. Oral administration of ascorbic acid attenuates endothelial dysfunction after short-term cigarette smoking by shortening its duration.

Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion.

CONTEXT: Although adrenal incidentalomas (AIs) are associated with a high prevalence of cardiovascular risk (CVR) factors, it is not clear whether patients with nonfunctioning AI (NFAI) have increased CVR. OBJECTIVE: Our objective was to investigate CVR in patients with NFAI. DESIGN AND SETTING: This case-control study was performed in a tertiary general hospital. SUBJECTS: SUBJECTS included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging. MAIN OUTCOME MEASURES: All participants underwent adrenal imaging, biochemical and hormonal evaluation, and the following investigations: 1) measurement of carotid intima-media thickness (IMT) and flow-mediated dilatation, 2) 2-hour 75-gram oral glucose tolerance test and calculation of insulin resistance indices (homeostasis model assessment, quantitative insulin sensitivity check, and Matsuda indices), 3) iv ACTH stimulation test, 4) low-dose dexamethasone suppression test, and 5) NaCl (0.9%) post-dexamethasone saline infusion test. RESULTS: Based on cutoffs obtained from controls, autonomous cortisol secretion was documented in 26 patients (cortisol-secreting AI [CSAI] group), whereas 34 exhibited adequate cortisol and aldosterone suppression (NFAI group). IMT measurements were higher and flow-mediated vasodilatation was lower in the CSAI group compared with both NFAI and C and in the NFAI group compared with C. The homeostasis model assessment index was higher and quantitative insulin sensitivity check index and Matsuda indices were lower in the CSAI and NFAI groups compared with C as well as in CSAI compared with the NFAI group. The area under the curve for cortisol after ACTH stimulation was higher in the CSAI group compared with the NFAI group and C and in the NFAI group compared with C. In the CSAI group, IMT correlated with cortisol, urinary free cortisol, and cortisol after a low-dose dexamethasone suppression test, whereas in the NFAI group, IMT correlated with area under the curve for cortisol after ACTH stimulation and urinary free cortisol. CONCLUSIONS: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.