Paolo Coruzzi

Association between salt sensitivity and insulin concentrations in patients with hypertension

This study was performed in 28 patients with mild to moderate hypertension, classified as being either salt sensitive or salt resistant on the basis of the percent decrement in mean arterial blood pressure (MAP) seen 7 days after daily salt intake was decreased from 220 to 30 mmol/L. Ten patients had a percent decrease of MAP > 10% and were defined as being salt sensitive. Salt resistance was defined as a percent decrease in MAP of < 3% and eight patients satisfied this criterion. Both plasma glucose and insulin concentrations following a 75-g oral glucose challenge were significantly higher after the high-salt diet in the salt-sensitive patients. Furthermore, there were correlations of marginal statistical significance between the decrease in MAP after the low-salt diet and the plasma glucose (r = 0.32, P < .10) and insulin (r = 0.38, P < .06) responses to oral glucose. These data are consistent with the view that there is an association between resistance to insulin-mediated glucose disposal and salt sensitivity in patients with high blood pressure.

Effects of Salt Sensitivity on Neural Cardiovascular Regulation in Essential Hypertension

Salt-sensitive hypertensive subjects, as defined by conventional categorical classification, exhibit alterations of autonomic cardiovascular control. The aim of our study was to explore whether, in hypertensive subjects, the degree of autonomic dysfunction and the level of salt sensitivity are correlated even when the latter is only mildly elevated and displays under-threshold values. Salt sensitivity of 34 essential hypertensive subjects was assessed on a continuous basis by the salt sensitivity index after low- and high-sodium diet. Beat-by-beat finger blood pressure was recorded after each diet period. Autonomic cardiovascular control was evaluated by spectral analysis of blood pressure and pulse interval and by assessment of spontaneous baroreflex sensitivity (sequence technique). Salt sensitivity and baroreflex sensitivity showed a negative relationship during low and high sodium intake, starting from low values of the salt sensitivity index. All spectral indexes of pulse interval, except the ratio between low- and high-frequency powers, were inversely related to salt sensitivity index after high sodium intake. In subjects with lower salt sensitivity, baroreflex sensitivity and pulse interval power in the high-frequency band were higher after high sodium intake than after low sodium intake. In contrast, subjects with a higher salt sensitivity index showed lower values of baroreflex sensitivity and pulse interval power in the high-frequency band, uninfluenced by salt intake. Our results provide the first demonstration of an impairment of parasympathetic cardiac control in parallel with the increase in the degree of salt sensitivity, also in subjects who were not ranked as salt-sensitive by the conventional categorical classification.

Detecting sodium-sensitivity in hypertensive patients: Information from 24-hour ambulatory blood pressure monitoring

Sodium sensitivity is an important cardiovascular risk factor for which a diagnosis requires a time-consuming protocol, the implementation of which is often challenging for patients and physicians. Our aim was to assess the reliability of an easier approach based on data from 24-hour ambulatory blood pressure monitoring performed in hypertensive subjects during daily-life conditions and habitual diet. We enrolled 46 mild to moderate hypertensive subjects who underwent 24-hour ambulatory blood pressure monitoring during usual sodium intake. Patients were divided into 3 classes of sodium sensitivity risk on the basis of ambulatory blood pressure monitoring data: low risk if dippers and a 24-hour heart rate ≤70 bpm; high risk if nondippers and a 24-hour heart rate of >70 bpm; intermediate risk with the remaining combinations (dippers with heart rate >70 bpm or nondippers with heart rate ≤70 bpm). Then patients underwent a traditional sodium sensitivity test for the dichotomous classification as sodium sensitive or sodium resistant and for evaluating the sodium sensitivity index. Prevalence of sodium-sensitive patients and mean value of sodium sensitivity index were calculated in the 3 risk classes. The sodium sensitivity index markedly and significantly increased from the low-risk to the high-risk class, being equal to 19.9±14.4, 37.8±8.3, and 68.3±17.0 mm Hg/(mol/day) in the low-risk, intermediate-risk, and high-risk classes, respectively (M±SEM). Also, the prevalence of sodium-sensitive patients increased significantly from the low-risk class (25%) to the intermediate-risk (40%) and high-risk (70%) classes. Thus, performance of 24-hour ambulatory blood pressure monitoring in daily-life conditions and habitual diet may give useful information on the sodium sensitivity condition of hypertensive subjects in an easier manner than with the traditional sodium sensitivity test approach.

Coronary artery anomalies: incidence, pathophysiology, clinical relevance and role of diagnostic imaging

Conventional coronary angiography is the gold standard for the diagnosis of coronary artery anomalies. Coronary anomalies are relatively rare findings in patients undergoing conventional coronary angiography for suspected obstructive coronary artery disease. Recently, the increasing performance of diagnostic techniques, such as electron beam tomography (EBT), magnetic resonance (MR) and, more recently, multislice computed tomography (MSCT), has enabled their application to cardiac imaging. MSCT, in particular, has a prominent role in coronary imaging due to its spatial and temporal resolution and threedimensional capabilities. We report the incidence and pathophysiology of coronary artery anomalies based on the capabilities of recent diagnostic tools with the aim of improving an accurate and noninvasive diagnostic approach.

Autonomic cardiovascular regulation in quiescent ulcerative colitis and Crohn's disease

Background  In inflammatory bowel diseases, changes in autonomic enteric regulation may also affect neural cardiovascular control. However, while cardiac autonomic modulation has been shown to be impaired in active ulcerative colitis, the occurrence of cardiovascular autonomic alterations, also in the quiescent phase of inflammatory bowel diseases, is still a matter of debate. The aim of our study was thus to explore the features of cardiovascular autonomic regulation in ulcerative colitis and Crohns disease during their remission phase.

Renal hemodynamics and natriuresis during water immersion in normal humans

The renal vascular and functional responses to acute “central hypervolemia” by water immersion to the neck were determined in six normal subjects. During isotonic-isooncotic expansion by water immersion there was a significant increase in urine flow from 1.1±0.1 to 6.9±1.0 ml/min (p<0.05) and sodium excretion from 99.1±8.8 to 300±28 μEq/min (p<0.05). Glomerular filtration rate did not change while renal blood flow significantly increased during water immersion. Deep intrarenal venous pressure (IRVP) increased from 18.2±1.4 to 32±1.7 mmHg (p<0.05) while mean arterial pressure was unchanged. This marked natriuresis seen during water immersion was associated with reduced renal vascular resistance and increased deep intrarenal venous pressure demonstrating that continued natriuresis could relate to increased capillary hydrostatic pressure.

Stress-ECG vs. CT coronary angiography for the diagnosis of coronary artery disease: a “real-world” experience

PurposeThis study aimed to evaluate the diagnostic accuracy of stress electrocardiogram (ECG) and computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis (≥50%) in the real world using conventional CA as the reference standard.Materials and methodsA total of 236 consecutive patients (159 men, 77 women; mean age 62.8±10.2 years) at moderate risk and with suspected coronary artery disease (CAD) were enrolled in the study and underwent stress ECG, CTCA and CA. The CTCA scan was performed after i.v. administration of a 100-ml bolus of iodinated contrast material. The stress ECG and CTCA reports were used to evaluate diagnostic accuracy compared with CA in the detection of significant stenosis ≥50%.ResultsWe excluded 16 patients from the analysis because of the nondiagnostic quality of stress ECG and/or CTCA. The prevalence of disease demonstrated at CA was 62% (n=220), 51% in the population with comparable stress ECG and CTCA (n=147) and 84% in the population with equivocal stress ECG (n=73). Stress ECG was classified as equivocal in 73 cases (33.2%), positive in 69 (31.4%) and negative in 78 (35.5%). In the per-patient analysis, the diagnostic accuracy of stress ECG was sensitivity 47%, specificity 53%, positive predictive value (PPV) 51% and negative predictive value (NPV) 49%. On stress ECG, 40 (27.2%) patients were misclassified as negative, and 34 (23.1%) patients with nonsignificant stenosis were overestimated as positive. The diagnostic accuracy of CTCA was sensitivity 96%, specificity 65%, PPV 74% and NPV 94%. CTCA incorrectly classified three (2%) as negative and 25 (17%) as positive. The difference in diagnostic accuracy between stress ECG and CTCA was significant (p<0.01).ConclusionsCTCA in the real world has significantly higher diagnostic accuracy compared with stress ECG and could be used as a first-line study in patients at moderate risk.RiassuntoObiettivoScopo del presente lavoro è stato valutare l’accuratezza diagnostica dell’elettrocardiogramma sotto stress (stress-ECG) e dell’angiografia coronarica con tomografia computerizzata (CT-CA) nell’individuazione delle stenosi coronariche significative (riduzione del lume coronarico ≥50%) vs l’angiografia coronaria convenzionale (CAG) basando la valutazione sulla refertazione clinica.Materiali e metodiDuecentotrentasei pazienti consecutivi (159 maschi, 77 femmine, età media 62,8±10,2 anni) a rischio intermedio con sospetta malattia coronarica sono stati arruolati per lo studio e sottoposti a stress-ECG, CT-CA e CAG. Per la scansione CT-CA sono stati iniettati endovena 100 ml di mezzo di contrasto. Tutti i pazienti sono stati quindi sottoposti a CAG. I referti dello stress-ECG e della CT-CA sono stati confrontati con la CAG quantitativa per la valutazione dell’accuratezza diagnostica.RisultatiSedici pazienti sono stati esclusi dall’analisi per stress-ECG e/o CT-CA di qualità inadeguata. La prevalenza di malattia è risultata del 62% nella popolazione complessiva (n=220), del 51% nella popolazione con stress-ECG e CT-CA confrontabili (n=147), e dell’84% nella popolazione con stress-ECG dubbio (n=73). Settantatre (33,2%) stress-ECG sono stati classificati come dubbi, 69 (31,4%) sono stati classificati come positivi e 78 (35,5%) sono stati classificati come negativi. Nell’analisi per paziente i valori dell’accuratezza diagnostica dello stress-ECG sono risultati: sensibilità 47%, specificità 53%, valore predittivo positivo 51%, valore predittivo negativo 49%. Quaranta (27,2%) pazienti sono stati erroneamente classificati come negativi. Trentaquattro (23,1%) pazienti che non avevano stenosi significative sono stati incorrettamente classificati come positivi. I valori dell’accuratezza diagnostica della CT-CA sono risultati: sensibilità 96%, specificità 65%, valore predittivo positivo 74%, valore predittivo negativo 94%. Tre (2%) pazienti sono stati erroneamente classificati come negativi. Venticinque (17%) pazienti che non avevano stenosi significative sono stati incorrettamente classificati come positivi. La differenza di accuratezza diagnostica è risultata significativa (p<0,01).ConclusioniLa CT-CA nel mondo reale mostra una accuratezza diagnostica significativamente superiore allo stress-ECG e potrebbe essere utilizzata in prima istanza nei pazienti a rischio intermedio.

Calcium and sodium handling during volume expansion in essential hypertension

To evaluate the actual role of extracellular fluid volume (ECFV) expansion per se in modulating the rate of urinary calcium excretion, a thermoneutral water immersion (WI) study was conducted in 10 normal subjects and 30 patients with essential hypertension. Central hypervolemia by 2 hours of WI caused a significant diuretic and natriuretic response (P < .005) in normal subjects; no significant changes were detected in urinary calcium and magnesium excretion. WI provoked either an appropriate or exaggerated natriuresis (P < .001) in 21 hypertensive patients; these subjects also exhibited a highly positive correlation between urinary sodium and calcium excretion during WI (P < .001). In the remaining nine hypertensive patients, WI produced a significant diuretic response, but a barely discernible (P = NS) natriuresis (inappropriate response). These subjects also exhibited a significant reduction of urinary calcium (P < .001) and magnesium (P < .01) excretion. The data indicate that (1) volume expansion per se may have a role in regulating calcium excretion in hypertensive subjects; (2) a calcium leak may be attributable to a close relationship between urinary sodium and calcium metabolism, and causally related to a disturbance of sodium and volume homeostasis in hypertension.

Effects of ‘Central Hypervolemia’ by Water Immersion on Renin-Aldosterone System and ACTH-Cortisol Axis in Hemodialyzed Patients

Water immersion up to the neck (WI) results in a central hypervolemia; the increased atrial pressure, evoked by this maneuver, stimulates low pressure receptors (LPR) which exert tonic inhibition on sympathetic activity and suppresses both the renin (PRA)-aldosterone (PA) system and the ACTH-cortisol axis in normal man. In hemodialyzed patients (HP), in whom autonomic neuropathy has been frequently found, PRA and ACTH were not suppressed during WI while plasma cortisol and PA were reduced. Other modulators, like dopamine, are supposed to be involved in regulating cortisol and PA levels in HP.

Water immersion and salt-sensitivity in essential hypertension.

It has been demonstrated that an exaggerated natriuretic response to central hypervolaemia is not necessarily associated with hypertension; many hypertensive subjects manifest either an appropriate or a blunted natriuresis in response to ECFV expansion attained by head-out water immersion. In this study, we tested the hypothesis that an underlying condition of salt-sensitivity may explain the heterogeneity of the natriuretic response of essential hypertension. Both salt-sensitivity tests and 2h water-immersion studies were randomly performed in 18 untreated essential hypertensives under a selected and controlled diet. Salt-sensitivity was defined as a significant drop in mean arterial pressure of 10% or greater, calculated as the difference between the average of the 25 readings under the high and the low salt period. Water immersion did result in a significant natriuretic and calciuretic response in the whole hypertensive group (n = 18, p < 0.001 and p < 0.05, respectively), while the examination of the individual excretion disclosed either exaggerated and appropriate or blunted urinary response. When the hypertensive group was classified in relation to salt-sensitivity, the greater fall in mean arterial pressure during low salt diet (salt-sensitivity) was associated with the more pronounced natriuretic response during water immersion (r = -0.66, p < 0.003). An identical correlation (r = -0.58, p < 0.01) was also found between changes in mean arterial pressure (low salt diet) and urinary calcium excretion (water immersion) in the same hypertensives. The water immersion-induced suppression of plasma aldosterone and the increase in plasma atrial natriuretic peptide did result from comparable magnitude in the salt-sensitive and in salt-resistant subjects.(ABSTRACT TRUNCATED AT 250 WORDS)