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A new method for the detection by flow cytometry of anti-double-stranded DNA antibodies and of circulating immune complexes (IC) containing endogenous DNA (IC-eDNA) is described. From each serum sample, two samples were taken, one was used to detect IC-eDNA. The other to detect anti-DNA antibodies was incubated with calf thymus DNA. ICs were isolated by polyethylene glycol precipitation or by cryoprecipitation, after which immunoglobulins were labeled with FITC-conjugated anti-human globulin. Serum samples from 63 systemic lupus erythematosus (SLE) patients, 32 incomplete lupus, and 87 control patients were tested. Detection of anti-dsDNA antibodies by flow cytometry had a diagnostic sensitivity and specificity almost comparable to routine tests, the fluorescent enzyme immunoassay EliA™-dsDNA test, and the ultrasensitive Crithidia luciliae indirect immunofluorescence test. In 21 (33%) out of 63 SLE serum samples, IC-eDNA was detected. In these samples, free anti-dsDNA antibodies were hardly detectable or undetectable by flow cytometry or by routine tests. When anti-DNA antibodies are neutralized by endogenous DNA and can no longer be detected by routine tests, the serologic diagnosis and the follow-up of relapses in patients with SLE is compromised. To overcome this obstacle, we propose an accessible solution: the detection of circulating IC-eDNA by flow cytometry., Competing Interests: The authors have declared that no conflict of interest exists., (Copyright © 2019 Nisen Abuaf et al.)

Background: The prognostic value of screening multiple target organ damages (TODs) in hypertensive subjects has not been extensively studied. We estimated the prognostic value of considering 3 TODs in estimating the 10-year survival in hypertensive subjects., Methods: At baseline 1,848 out of a cohort of 1,963 hypertensive patients had a previous cardiovascular disease (CVD) or assessments of 3 TODs: Modification in Diet in Renal Disease (MDRD) <60ml/min or albuminuria >300mg/day, Sokolow index >3.5 mV, and advanced hypertensive retinopathy (grades 3 and 4 of Keith-Wagener-Barker classification). The cohort was divided into 5 groups: 0 TOD (N = 978), 1 TOD (N = 308), 2 TODs (N = 94), 3 TODs (N = 30), and previous CVD (N = 438)., Results: After 10 years of follow-up, we observed 418 deaths of which 254 from cardiovascular cause. The adjusted hazard ratios for the major cardiovascular risk factors showed a progressive risk associated with the number of TODs. For all-cause death, the hazard ratios [95% confidence intervals] vs. 0 TOD of the other 4 groups were 1.91 [1.39-2.63], 1.99 [1.28-3.10], 4.33 [2.42-7.72], and 3.09 [2.35-4.05], respectively. For cardiovascular death, the hazard ratios [95% confidence intervals] were of the same order of magnitude: 2.14 [1.38-3.32], 2.12 [1.15-3.89], 4.22 [1.83-9.72], and 4.24 [2.95-6.11], respectively., Conclusions: Our results indicate that hypertensive patients with several TODs had a worst outcome. Thus, it seems important to screen for multiple TODs in hypertension; especially check for severe hypertensive retinopathy in patients with left ventricular hypertrophy (LVH) and renal damage., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The relationship between blood pressure (BP) and cardiovascular diseases has been extensively documented. However, the benefit of anti-hypertensive drugs differs according to the type of cardiovascular event. Aortic stiffness is tightly intertwined with BP and aorta cross-talk with small arteries. We endeavored to elucidate which BP component and type of vessel remodeling was predictive of the following outcomes: fatal myocardial infarction (MI), fatal stroke, renal -, coronary- or cerebrovascular-related deaths. Large vessel remodeling was estimated by an aortography-based aortic atherosclerosis score (ATS) while small vessel disease was documented by the presence of a hypertensive retinopathy. We included 1031 subjects referred for hypertension workup and assessed outcomes 30 years later. After adjustment for major risk factors, ATS and pulse pressure (PP) were predictive of coronary events while mean BP (MBP) and retinopathy were not. On the contrary, MBP was predictive of cerebrovascular and renal related deaths while ATS and PP were not. Retinopathy was only predictive of cerebrovascular related deaths. Lastly, the aortic atherosclerosis phenotype and increased PP identified patients prone to develop fatal MI whereas the retinopathy phenotype and increased MBP identified patients at higher risk of fatal stroke. These results illustrate the particular feature of the resistive coronary circulation comparatively to the brain and kidneys' low-resistance circulation. Our results advocate for a rational preventive strategy based on the identification of distinct clinical phenotypes. Accordingly, decreasing MBP levels could help preventing stroke in retinopathy phenotypes whereas targeting PP is possibly more efficient in preventing MI in atherosclerotic phenotypes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: In patients free from overt cardiac disease, R wave in aVL lead (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by transthoracic echocardiography. The aim of the present study was to extend this finding to other settings (cardiomyopathy or conduction disorders), by comparing ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR)., Methods: In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR LVH cut-offs used were 83 g/m2 in men and 67 g/m2 in women., Results: RaVL was independently correlated with LVMI in patients with or without myocardial infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently correlated with LVMI and LV enlargement only in patients without MI. In the whole cohort, RaVL had area under receiver-operating characteristic curve of 0.729 (specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance of RaVL was remarkable in women, in Caucasians, and in the presence of right bundle branch block. It decreased in case of MI. Overall, it is proposed that below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH. Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be used. Using this algorithm allowed classifying appropriately 85% of the patients., Conclusions: Our results showed that RaVL is a good index of LVH with a univocal threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL in some conditions, namely LV enlargement to increase its performance., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: Primary aldosteronism could exert a negative feedback on prorenin secretion, of possibly different magnitude, whether it is related to an aldosterone-producing adenoma (APA) or an idiopathic hyperaldosteronism (IHA). The objectives of this study were to evaluate the level of prorenin in three subgroups: APA, IHA, and essential hypertension; and the performance of the aldosterone-to-prorenin ratio (APR) for the diagnosis of an APA., Methods: Seven hundred and forty-six hypertensive patients with a standardized work-up, including a prorenin measurement, were considered. Ninety-six patients without neutral treatment and 38 patients with other forms of secondary hypertension were excluded. APA and IHA were categorized according to computed tomography scan, adrenal venous sampling, pathological analysis and improvement of hypertension after surgery., Results: Thirty-five patients had a diagnosis of APA, 57 of IHA and 504 of essential hypertension. Prorenin was lower in APA and IHA than in essential hypertension (32.9, 40.4 and 50.3  pg/ml, respectively; P < 0.001). APR was higher in patients with APA and IHA than in those with essential hypertension (24.0, 11.8, and 4.0  pmol/l per pg/ml, respectively; P < 0.001). The APR was more discriminant than the aldosterone-to-renin ratio to identify APA compared to IHA (area under the receiver operating curve at 0.750 and 0.639, respectively; P = 0.04). The optimal cut-off values were 22  pmol/l per pg/ml for APR (sensitivity 57.0%, specificity 93.0%) and 440  pmol/l per pg/ml for aldosterone-to-renin ratio (sensitivity 54.3%, specificity 82.5%)., Conclusion: Primary aldosteronism and particularly its most caricatural form, that is APA, seems associated with a lower level of prorenin than essential hypertension. The APR could be included in the diagnostic strategy of APA.

Objectives: Our study aimed at determining the interaction between the prognostic value of diastolic blood pressure (DBP) and aortic atherosclerosis (ATS)., Background: With aging, equal systolic blood pressures (SBPs) become associated with low DBPs; i.e., high pulse pressures (PPs) become associated with a high risk of cardiovascular death. This association is usually ascribed to aortic stiffening with age but the precise impact of low DBP per se is yet uncertain., Methods: 938 hypertensive patients recruited in the seventies had an aortic ATS score at pretreatment aortography. All-cause and cardiovascular deaths were assessed 20 years later. The prognostic values of DBP and SBP were assessed by a multivariate Cox regression model and their interactions with ATS examined., Results: In the presence of ATS, an increase of 10 mmHg in DBP was associated with a protective effect: hazard ratios 0.84 [0.72-0.99] for cardiovascular death and 0.88 [0.78-1.00] for all-cause death. However, in the absence of ATS, DBP had no prognostic value: hazard ratios 1.05 [0.89-1.23] for cardiovascular death and 0.99 [0.88-1.11] for all-cause death (p for interaction: 0.061 and 0.087, respectively). No interaction was found between SBP and ATS (p for interaction > 0.40)., Conclusions: The prognostic values of DBP and aortic atheroma are not superimposable; yet, they are tightly connected: a low DBP is disadvantageous only in the presence of a pathologic aorta. Aortic atherosclerosis may explain, at least partly, in some high risk populations, the J-shape of the already reported DBP-outcome relationship., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Frequency and titers of autoantibodies in patients with sickle-cell disease (SCD) have been reported as relatively high. In a prospective study of 88 patients, we examined this "hyper-autoreactivity" and its clinical consequences., Methods: For 1 year, patients with SCD were screened for the presence in their serum of antinuclear, anti-double-stranded DNA, antiextractible nuclear antigens, anticardiolipin antibodies, and rheumatoid factors. A population of 85 sex-matched individuals of similar ethnic origin served as controls., Results: Whereas prevalence of autoantibodies did not differ between the 2 groups, the type and rate of antinuclear antibodies were different. Autoantibodies from the SCD patients showed various immunofluorescence patterns, whereas only speckled patterns at low titers were present in controls. No antibody specificity was found in either group. SCD patients and controls displayed similar rates of anticardiolipin antibodies, but the SCD patients tended to be more frequently positive for rheumatoid factors. Six-year followup of the SCD patients did not provide any clinical evidence for onset of an autoimmune disease, except for 1 patient who developed rheumatoid arthritis, with increasing antinuclear antibodies followed by emergence of specific markers 5 years later., Conclusion: Patients with SCD displayed high titers of autoantibodies. This observation may be due only to immune activation and/or dysfunction in SCD, as neither pathogenic specificity of autoantibodies nor autoimmune clinical signs appeared in the majority of cases in our study.

Objective: Estimating the risk entailed by classical risk factors like blood pressure (BP) or serum cholesterol may be difficult because of their variability and the often unknown duration of exposure. Having variables integrating the impact of those classical risk factors on the cardiovascular system would probably aid the prediction of cardiovascular events. The present study aimed at determining whether cardiac baroreflex sensitivity (BRS), correlates with several risk factors and thus is a good candidate for being such an integrative variable. As a comparison, left ventricular mass (LVM), pulse wave velocity (PWV), and creatinine were also tested for association with risk factors., Design: A total of 302 subjects referred for hypertension, were considered. They had a 24-h BP recording and a determination of BRS by two different methods (sequence and alpha coefficient), in two different positions (lying and standing). They were also tested for the presence of left ventricular hypertrophy (LVH) (by echocardiography and electrocardiogram) and had a PWV measurement. Biological testing included serum lipids, blood glucose, creatinine, proteinuria and urinary excretion of microalbumin., Results: There was a strong correlation between the two methods of BRS measurement in each position (P < 0.001). BRS determined by the sequence method in the lying position was correlated significantly and independently with age, 24-h systolic BP, heart rate, and serum cholesterol with P values < 0.001, < 0.001, < 0.01, and < 0.05, respectively. In an univariate analysis, BRS was also correlated with echocardiographic LVM index (r = -0.21, P < 0.05) and PWV (r = -0.27, P < 0.001), which possibly reflects its dependence on both vascular and cardiac damages., Conclusion: The present study supports the hypothesis that BRS could encompass the impact over time of several risk factors on the cardiovascular system. Thus, it may constitute a valuable parameter in assessing more precisely the risk of cardiovascular events.

At the start of the eighties, in the wake of the good results obtained with aspirin in secondary prevention, two studies were launched aimed at testing the effect of aspirin on the primary prevention of myocardial infarction. The results published in 1988 and 1989 were divergent: the study conducted by British doctors showed no benefit with aspirin, that conducted by American doctors showed a very distinct benefit concerning myocardial infarction but no advantage for cerebral vascular accidents. Besides, in both studies an additional risk of haemorrhagic cerebral vascular accident was described. Methodological reasons were the origin of these facts, but it resulted in a certain confusion as to the practical conduct to adopt. Ten years later it is much more clear after the publication of three supplementary trials. The benefits of aspirin in terms of prevention of myocardial infarction are certain and considerable, at the price of a haemorrhagic risk equally certain but moderate. On the other hand, questions remain concerning the preventive effect of aspirin on cerebral vascular accidents and also on the expected benefits in the female sex. In practice, the prescription of aspirin with the objective of primary prevention must take into account the absolute benefit which can be expected. This is a function of the individual absolute risk before treatment which therefore signifies an evaluation based on the risk factors. Only subjects exposed to a substantial risk before treatment are likely to benefit from aspirin. For the others, the risks linked with aspirin could counterbalance its preventive advantages.