Cholesterol lowering treatment restores blood global DNA methylation in chronic kidney disease (CKD) patients.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is characterized by increased oxidative stress (OS). In consideration of the well-known link between OS and DNA methylation we assessed DNA methylcytosine (mCyt) concentrations in CKD patients at baseline and during cholesterol lowering treatment. METHODS AND RESULTS: DNA methylation and OS indices (malonyldialdehyde, MDA; allantoin/uric acid ratio, All/UA) were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40 mg/day, ezetimibe/simvastatin 10/20 mg/day, or ezetimibe/simvastatin 10/40 mg/day) and 30 age- and sex-matched healthy controls. DNA methylation was significantly lower in CKD patients vs. controls (4.06 ± 0.20% vs. 4.27 ± 0.17% mCyt, p = 0.0001). Treatment significantly increased mCyt DNA concentrations in all patients (4.06 ± 0.04% at baseline; 4.12 ± 0.03% at 4 months; 4.17 ± 0.03% at 8 months; and 4.20 ± 0.02% at 12 months, p = 0.0001 for trend). A trend for a greater effect on DNA methylation was observed with combined treatment ezetimibe/simvastatin 10/40 mg/day (+5.2% after one year treatment). The treatment-associated mCyt increase was significantly correlated with the concomitant reduction in MDA concentrations and All/AU ratios. CONCLUSION: Our results demonstrate that CKD patients have a lower degree of DNA methylation and that cholesterol lowering treatment restores mCyt DNA concentrations to levels similar to healthy controls. The treatment-associated increase in DNA methylation is correlated with a concomitant reduction in OS markers. The study was registered at clinicaltrials.gov (NCT00861731).

Metals in plasma of nonagenarians and centenarians living in a key area of longevity.

The concentration of calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn) and selenium (Se) in plasma of 76 nonagenarians (mean age, 89.0±6.3 years), 64 centenarians (mean age, 101±1 years) and 24 middle-aged subjects as controls (mean age 61.2±1.1 years), was determined by sector field inductively coupled plasma mass spectrometry. All the subjects lived in Sardinia, an Italian island, that has the higher prevalence of centenarians than in other European countries. A comparison among the three classes of age showed a significant depletion of Ca, Co, Fe, Mn and Se (all p<0.001) in nonagenarians and centenarians with respect to controls. In particular, the geometric mean (GM) values of Ca, Co, Fe, Mn and Se were: 94.1 µg/ml, 0.46 ng/ml, 1314 ng/ml, 2.47 ng/ml and 111 ng/ml in controls; 87.6 µg/ml, 0.22 ng/ml, 815 ng/ml, 1.07 ng/ml and 88.9 ng/ml in nonagenarians; 87.0 µg/ml, 0.29 ng/ml, 713 ng/ml, 1.27 ng/ml and 81.9 ng/ml in centenarians. The highest inverse relationship with age was observed for Fe (p<0.001; ρ=-0.352) and Se (p<0.001; ρ=-0.417). This trend was also observed when data were sorted by gender. On the other hand, Cu and Mg levels in plasma remained substantially unchanged during aging. As regards Cu, it was significantly higher in females than in males in controls (GM, 1294 ng/ml vs. 1077 ng/ml; p=0.012), in nonagenarians (GM, 1216 ng/ml vs. 1081 ng/ml; p=0.011) as well as in centenarians (GM, 1226 ng/ml vs. 1152 ng/ml; p=0.045) and in hypertensive subjects with respect to healthy people (GM, 1215 ng/ml vs. 1129 ng/ml; p=0.021). These data can be used to enhance knowledge and support the research on: i) metals involved in aging in areas with high rates of human longevity; ii) variables (gender, lifestyle habits and health status) as critical determinants in aging; and iii) mineral intake and supplementation at older age affecting the healthy aging.

[Cardiac output studied by a non invasive method in hypertensive patients]. / Etude du débit cardiaque par une méthode non invasive chez des hypertendus.

We measured by thoracic bioimpedance (BoMed, NCCOM3-R7) non invasive cardiac index (CI), stroke index (SI) and systemic vascular resistance index (SVRI) in 48 hypertensive patients (OMS) compared to 30 normotensive. The mean arterial pressure (MAP) and the SVRI were significantly higher in the hypertensive group while the CI are significantly lower, as that was shown in previous invasive studies. We found an inverse correlation between age and CI (r = -.30, p < or = .05) in relation with a negative correlation between SI and age (r = -.35, p < or = .05) and no correlation between heart rate and age. Furthermore we divided normotensive and hypertensive patients in three groups of CI (low CI < 2.8 l/min/m2, 2.8 < or = normal CI < or = 4.2 l/min/m2, high CI > 4.2 l/min/m2) and in three groups of SVRI (low SVRI < 1660 Flohms/m2, 1660 < or = normal SVRI < or = 2580 Flohms/m2, high SVRI > 2580 Flohms/m2). Despite CI diminution in hypertension, high CI percentage's was the same in normotensive and hypertensive patients. In conclusion, these results confirm previous studies by using a simple, easy, non invasive and reproducible method.

[Adjustment of double-chamber pacemakers in VDD mode by measurement of thoracic electric bio-impedance]. / Réglage des stimulateurs double chambre en mode VDD par mesure de la bio-impédance electrique thoracique.

An optimal atrioventricular interval (AVI) was sought in 6 patients with a double chamber pacemaker by an non-invasive technique: measurement of stroke volume by thoracic bioimpedance. This method proved to be easy and reliable in practice when there was only one pacing spike (VDD mode). It confirmed the existence of a variable optimal AVI according to individual patients: 250 ms (3 patients), 200-250 ms (1 patient), 150 ms (1 patient), 75-100 ms (1 patient). The value of optimal AVI is unpredictable since it depends upon individual electrophysiological and hemodynamic parameters. In a patient with severe mitral incompetence, Echo-Doppler provided evidence of end-diastolic ventriculo-atrial regurgitation at middle and long AVI, while a short AVI enabled elimination of end-diastolic regurgitation and a 15.45 per cent improvement in stroke volume. In two patients with a long optimal AVI (250 ms), a programmed short AVI (75 ms) paradoxically appeared to be more favourable than a middle AVI (150 ms).

[Cardiac mass, ventricular relaxation parameters and their correlation with blood pressure during rest and ambulatory monitoring]. / Paramètres de masse cardiaque, de relaxation ventriculaire et leurs corrélations avec la pression artérielle enregistrée au repos et en ambulatoire.

UNLABELLED: A resting blood pressure (Dynamap, 8AM-8PM, one recording every 15 minutes) has been recorded among 60 patients; mean age: 51 +/- 14 years (24 females, 36 males; 3 normotensive and 57 hypertensive WHO) and a echocardiogram TM and two-dimensional with doppler in order to measure the interventricular septum thickness, Left Ventricular Posterior Wall Thickness and the left Ventricular Internal diameter with which we can calculate the myocardial mass (MM, Devereux formula) and the myocardial mass index using the body surface. Furthermore ventricular relaxation has been studied (A/E, PHT) by using doppler echocardiogram. During the same week an ambulatory blood pressure (Nippon Colin 8AM-8PM one reading every 15 minutes) has been recorded. The blood variables are the mean of the recording, systolic, diastolic, mean. We have confirmed the conclusion between blood pressure and left ventricular mass by using resting and ambulatory blood pressure recordings. But it does not exist any significant difference within we compare the correlations coefficients (Hotteling's Test with Williams modification) obtained with two devices. In revenge this difference exists with ventricular relaxation index A/E to MBP: mMBPr = 0.51, mMBPa = 0.34 (p less than 0.05), and PHT to MBP: mMBPr = 0.49, mMBPa = 0.31, (p less than 0.05) and to the SBP: mSBPr = 0.54, mSBPa = 0.35, (p less than 0.05). CONCLUSION: the relationship between blood pressure and myocardial mass and by, the heart effect from hypertension can be studied by using in any case resting and ambulatory blood pressure recordings. This will confirm the hypothesis in which the blood pressure recordings multiplication is more important than the way of recording it.(ABSTRACT TRUNCATED AT 250 WORDS)

[Blood pressure variability and morbidity]. / Variabilité tensionnelle et morbidité.

In a previous study (resting blood pressure profile, Dinamap) we have confirmed the correlations between blood pressure and left ventricular mass (myocardial hypertrophy being one of the morbidity criteria in Hypertension) and we have demonstrated the absence of significant difference (Fisher's z Test) with the results of ambulatory recordings found in literature. Furthermore, we have showed a weaker correlation between absolute variability (AV) and left ventricular mass (LVM). If indeed there exists a cause-effect relationship between the AV increase and the LVM increase, a relative independence between VA and blood pressures mean (mBP) should still be demonstrated. In order to do that we have used the factorial analysis (main components analysis) with which a small number of independent factors can be isolated from a large number of correlated variables. A resting blood pressure (Dinamap, 8AM-8PM, one reading every 15 minutes) has been recorded among 551 patients (259 females, 292 males; 109 normotensive WHO, 442 hypertensive WHO) and an echocardiogram TM and two-dimensional in order to measure the interventricular septum thickness (IVST), the posterior wall thickness (PWT) and the left ventricular internal diameter (LVID) with which we can calculate the myocardial mass (MM, Devereux formula) and the myocardial mass index (MMI) using the body surface (BS). The blood pressure variables are the means of the recordings (mBP): systolic (mSBP), diastolic (mDBP), mean (mMBP) and their standard deviations (SSD, DSD, MSD) corresponding to the AV. We have studied the heart rate (HR) with its standard deviation (HRSD) and age.(ABSTRACT TRUNCATED AT 250 WORDS)

[Relationship between heart mass and semi-ambulatory pressure profiles]. / Relation masse cardiaque et profils tensionnels semi-ambulatoires.

This work was undertaken with 420 patients (90 normotensives: casual blood pressure less than or equal to 140/90 mmHg and 330 hypertensives) in which was recorded a semi ambulatory blood pressure profile (Dinamap 8AM-8PM, a reading every fifteen minutes). On the same day an echocardiogram was performed. We have correlated the left ventricular mass, the left ventricular mass index, the interventricular septum, the left ventricular cavity volume and the left ventricular posterior wall with casual blood pressure, average daily blood pressure standard deviation and variation coefficient for mean blood pressure, systolic blood pressure and diastolic blood pressure. Analysis by sex, left ventricular mass index and blood pressure level (normotensive, hypertensive): we observe a left ventricular hypertrophy in normotensive males (18 p. 100) and hypertensive ones (39.8 p. 100), in normotensive females (15 p. 100) and hypertensive ones (33.3 p. 100). Overall in 420 patients: excellent correlation (p less than 0.001) between average daily blood pressure, casual blood pressure and the four echocardiographic parameters except for left ventricular cavity volume. But correlation is better (z test of Fisher) with average daily blood pressure than with casual blood pressure. No difference exists between results obtained in women (194) and men (226). Concerning variability, four observations: there exists a correlation between standard deviation, left ventricular mass index, interventricular septum, left ventricular posterior wall (only for standard deviation of MBP). No correlation with coefficient correlation except for the MBP with septum in women. The correlation for the standard deviation are weaker than with average daily blood pressure. They are better with the septum than with other echocardiographic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

[Atrioventricular block, a complication of radiotherapy of the mediastinum]. / Bloc auriculo-ventriculaire, complication de la radiothérapie du médiastin.

Cardiac complications of mediastinal irradiation usually concern the pericardium, the ventricular myocardium and the coronary arteries. We report the case of a 42-year old woman who experienced a syncopal atrioventricular (AV) block 12 years after irradiation of a mediastinal Hodgkin's lymphoma. Electrophysiological recordings showed infranodal conduction disturbances. A review of the literature yielded only 12 cases of syncopal radiation-induced AV block. This case highlights the risk of syncopal AV blocks occurring a long time after mediastinal irradiation and leading to severe damage of the His bundle and its branches. The presence, as in our patient, of an associated right ventricular outflow tract stenosis confirms the importance and severity of radiation-induced cardiac lesions.

[Blood pressure variation]. / Etude de la variabilité tensionnelle.

A blood pressure profile at rest was recorded in 2,000 patients (1,069 females, 931 males) by DINAMAP 845 (from 8 AM to 8 PM. a record every fifteen minute). The limit between normotensive and hypertensive patients in this settled by WHO (BP = 160/95 mmHg). The analysis of percentage of pathological values (BP greater than 160/95 mmHg) allowed us to identify eight type of recordings. Normal (295), Border line hypertension less than or equal 20 p. 100 of pathological values (573), Paroxysmal hypertension (58), hypertension with predominance (963) of whom 484 with systolic predominance and 479 with diastolic predominance, Isolated systolic hypertension (15), Isolated diastolic hypertension (47), hypertension without predominance (15) and Permanent hypertension (82). The variability of blood pressure was studied by using the coefficient of variation = p. 100 of standard deviation/mean.(ABSTRACT TRUNCATED AT 250 WORDS)

[Analysis of 1,400 blood pressure profiles]. / Analyse de 1,400 profils tensionnels.

Hypertension may be defined by 3 criteria obtained by indirect, non invasive, automatic measurement of blood pressure using the DINAMAP device analyses the profile obtained over a 12 hour period (one recording every fifteen minutes): percentage of abnormal values (BP greater than 160/95 mm Hg), average values of systolic, diastolic and mean BP, variability (standard deviation of means), The analysis was based on 1,400 profiles recorded from 174 normotensive and 1,226 hypertensive patients. The following observations were made: the largest group was that of patients with predominantly diastolic hypertension under 60 years of age (81.3 p. 100 vs. 18.9 p. 100 systolic hypertension) and predominantly systolic hypertension over 60 years of age (68.9 p. 100 vs. 31.1 p. 100 diastolic hypertension), borderline hypertension (between 1 and 20 p. 100 of pathological values) is observed in 34.5 p. 100 of hypertensive patients under 60 years of age, and 21.8 p. 100 of patients over 60 years of age. This form of hypertension may be managed without drug therapy but requires a control blood pressure profile at least once a year, the other groups of patients were much smaller: pure diastolic hypertension (4.8 p. 100 in the under 60's, 0.6 p. 100 in the over 60's); pure systolic hypertension (1/1,226 cases of hypertension), permanent hypertension (5.7 p. 100 in the under 60's and 4.4 p. 100 in the over 60's), paroxysmal hypertension (2.1 p. 100 in the under 60's and 5.6 p. 100 in the over 60's).(ABSTRACT TRUNCATED AT 250 WORDS)

[Study of the placebo effect by the pressure profile method]. / Etude de l'effet placebo par la méthode des profils tensionnels.

The effect of one tablet of placebo daily for 8 days on blood pressure was studied in 90 hypertensive patients, using the blood pressure profile method, with a 12-hour recording period (from 8 a.m. to 8 p.m) and readings every 15 minutes (Dinamam 845). Statistical analysis of the results showed no significant difference in diastolic, systolic and mean blood pressure in 50% of the cases. A significant decrease of about 10% in blood pressure without change in variability was observed in more than 20% (complete placebo effect) and in about 30% (total placebo effect) of the cases. A significant increase of about 8% on blood pressure was recorded in less than 20% of the cases. Almost 25% of the patients had a significant decrease in heart rate. There was no correlation between heart rate and blood pressure under placebo. These criteria, which are both qualitative and quantitative, can be taken as reference when the blood pressure profile method is used to evaluate the effectiveness of antihypertensive drugs.

[Delayed filling of the anterior interventricular artery. Apropos of 9 cases]. / Retard de remplissage de l'artère interventriculaire antérieure. A propos de 9 cas.

Selective coronary angiography has shown that typical angina pectoris may occur in the absence of atheromatous coronary stenosis. Other causes of these attacks of pain have been found: coronary spasm, small vessel disease, abnormal dissociation of haemoglobin or metabolic disturbances of the myocardial cell. Of all the patients undergoing coronary angiography in 1984 at the Centre Cantini, 9 had no classical coronary lesions but delayed filling of the left anterior descending artery. This syndrome was described for the first time in 1972 by Tambe as the "slow flow velocity syndrome". The aim of this study was to analyse the clinical, ECG and haemodynamic profiles of those patients. Five of them also underwent stress Thallium myocardial scintigraphy. An ergometrine provocation test was performed afterwards under ECG control. Delayed filling was appreciated by comparison with the other vessels and also by measuring the filling time which was two or three times longer than in a control series of 9 patients with angina and normal coronary arteries. The difference was statistically significant. These findings were only observed in strictly normal coronary vessels; they were reproducible and unaffected by the administration of nitrate derivatives. In our series all 9 patients were men with an average age of 51.4 years. One patient was asymptomatic and had a history suggestive of myocardial infarction, and 4 others had typical angina of effort: all had abnormal exercise stress tests. The other 3 patients had spontaneous atypical chest pain, normal resting ECG and a negative exercise stress test (impossible in one case). The five stress Thallium scintigraphies showed myocardial perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS)