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

PURPOSE: This 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 (> or =50%) in the real world using conventional CA as the reference standard. MATERIALS AND METHODS: A 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 > or =50%. RESULTS: We 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). CONCLUSIONS: CTCA 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.

Blood pressure changes after high- and low-salt diets: are intermittent arm measures and beat-by-beat finger measures equivalent?

The assessment of sodium sensitivity requires to measure the difference in mean arterial pressure (MAP) at the end of sodium-loading (SLoad) and sodium-depletion (SDepl) maneuvers with an arm-cuff manometer. Aim of this study is to evaluate whether MAP measuring devices based on the volume-clamp method at the finger can also be used for assessing sodium sensitivity. Sixty-eight normotensive volunteers underwent SLoad and SDepl diets in random order. MAP was simultaneously measured at the end of each diet with arm (Spacelabs 90207) and finger (Portapres model-2) cuff devices. The sodium sensitivity was assessed as the difference in MAP at the end of SLoad and SDepl diets (ΔMAP), and as salt-sensitivity index (SSI; SSI = ΔMAP divided by the difference in urinary-sodium-excretion rate at the end of the diets). Discrepancies between finger and arm-cuff devices in ΔMAP or SSI were evaluated by Bland and Altman analysis. Even if discrepancies between devices had null-fixed bias, results showed a significant proportional bias and large limits of agreement (between -25 and 25 mm Hg for ΔMAP, between -196 and 180 mm Hg mol(-1) per day for SSI). The SSI distribution over the group was larger, flatter and less symmetric if derived from finger-cuff rather than arm-cuff devices, and this influenced substantially the identification of salt-sensitive individuals. Therefore, the response of MAP to SLoad/SDepl diets and consequently the assessment of the salt-sensitivity condition depends importantly on the measurement site, and brachial measures should be preferred for consistency with literature and normative data.

Escape from the sodium-retaining effects of mineralocorticoids: is there a role for dopamine?

To investigate the possible role of dopamine, a catecholamine with natriuretic properties, in modulating the escape from the sodium-retaining effects of mineralocorticoids, we submitted six aldosterone-producing adenoma (APA) patients and six low-renin essential hypertensive patients to acute volume expansion by head-out water immersion with or without dopaminergic blockade by metoclopramide. Water immersion alone induced a marked, comparable natriuresis (P < 0.001) in both hypertensive groups where a slight reduction of already suppressed renin-angiotensin system and a marked stimulation of atrial natriuretic peptide was also observed (P < 0.03 and P < 0.002, respectively). Water immersion plus dopaminergic blockade by metoclopramide did not significantly affect the natriuresis observed during water immersion alone in APA patients; conversely, there was a blunted natriuretic response in low-renin hypertensives during water immersion plus metoclopramide, in comparison with that obtained during water immersion alone (P < 0.006). Furthermore, metoclopramide did prevent the suppression of plasma aldosterone levels produced by central volume expansion alone in low-renin hypertensives, although it did not affect plasma aldosterone levels during water immersion in APA patients. Our data suggest that dopaminergic blockade does not counteract the natriuretic ability of the other hemodynamic and humoral mechanisms involved in the escape phenomenon of APA patients, thus casting serious doubt on the possible role of dopamine in mediating the escape from the sodium-retaining effects of mineralocorticoids.

Abnormal renal responses to calcium entry blockade in normotensive offspring of hypertensive parents.

In nine young normotensive subjects with no family history of hypertension and nine age-matched normotensive subjects with one parent with essential hypertension, effective renal plasma flow (p-aminohippuric acid clearance), glomerular filtration rate (inulin clearance), and excretion of sodium and exogenously administered lithium were measured for 90 minutes before and after administration of a single 20-mg oral dose of the calcium entry blocker nifedipine. Segmental tubular handling of fluid and sodium was estimated using lithium clearance as a marker of proximal tubular reabsorption. Nifedipine did not cause any change in subjects with no family history of hypertension, but in those with one hypertensive parent there was a marked increase in effective renal plasma flow (from 644 +/- 39 to 847 +/- 42 [SEM] ml/min x 1.73 m2; p less than 0.001) and a decrease in filtration fraction (from 17.6 +/- 1.0 to 12.6 +/- 0.4%; p less than 0.001), while the glomerular filtration rate was unchanged, thus suggesting a prevailing efferent vasodilation. Sodium excretion rate (p less than 0.02) and fractional sodium excretion (p less than 0.025) increased slightly but significantly in subjects with one hypertensive parent, but not in normotensive subjects with no family history of hypertension. Lithium clearance also rose (from 29.0 +/- 2.0 to 32.8 +/- 1.9 ml/min, p less than 0.001), and the derived value of fractional proximal reabsorption diminished (from 75.8 +/- 1.0 to 71.3 +/- 1.2%, p less than 0.001). Estimated distal delivery of sodium and absolute distal sodium reabsorption both increased significantly (p less than 0.005), while fractional distal sodium reabsorption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Potassium depletion and salt sensitivity in essential hypertension.

To evaluate the actual role of potassium depletion on blood pressure, 11 hypertensive patients were placed on a 10-day isocaloric diet providing a daily potassium intake of either 18 or 80 mmol, with each subject serving as his or her own control; the intake of sodium (220 mmol/day) and other minerals was kept constant. On day 11 each patient was also subjected to central volume expansion by water immersion associated with either normal or low potassium intake. After a 10-day period of low potassium intake, systolic blood pressure increased (P < 0.02) by 5 mm Hg, whereas serum potassium decreased (P < 0.001) by 0.9 mmol/L; no significant changes in urinary sodium and a marked increase in urinary calcium excretion (P < 0.001) were found during the 10-day low potassium intake. PRA (P < 0.02) and plasma aldosterone (P < 0.04) concentrations also decreased during low potassium intake in hypertensive patients. Even though an identical natriuretic response was found during the water immersion experiments with either high or low potassium in the whole hypertensive group, the evaluation of hypertensive subjects in relation to salt sensitivity enabled us to disclose pronounced differences in the natriuretic and calciuretic response. In fact, although an impaired natriuretic ability and moderate calcium loss were particularly found during water immersion in those hypertensive subjects exhibiting a lower salt sensitivity index, a predominant calcium depletion appeared to be the most important consequence of potassium depletion in the hypertensive subjects with a higher salt sensitivity index. By confirming that potassium depletion may exacerbate essential hypertension, our data also suggest that not only sodium restriction, but also potassium and calcium supplementation, could be particularly advisable in salt-sensitive hypertensive patients.

Dopamine blockade abolishes the exaggerated natriuresis of essential hypertension.

We studied natriuresis during central hypervolaemia by immersing eight normal subjects and eight patients with uncomplicated essential hypertension up to the neck in water, either in the absence (study 1) or presence (study 2) of dopamine blockade by metoclopramide. Water immersion without metoclopramide induced an exaggerated natriuresis in hypertensives compared with normotensives (P less than 0.001). This occurred in the presence of identical hormonal (plasma renin activity, plasma aldosterone and prolactin), renal (creatinine clearance) and pressor responses in both groups (study 1). The marked natriuresis seen during water immersion alone in normotensives was significantly blunted (P less than 0.02) but not abolished during water immersion with addition of metoclopramide. On the other hand, the exaggerated natriuresis found in hypertensives during water immersion alone was completely abolished during water immersion plus dopamine blockade by metoclopramide (study 2). Similar hormonal, renal and pressor changes were detected in both normotensive and hypertensive subjects during water immersion plus metoclopramide administration. Our data demonstrate that metoclopramide abolishes the exaggerated natriuretic response seen in hypertensives during volume expansion produced by water immersion, and suggest that dopamine may play a critical role in mediating the hypernatriuresis of essential hypertension.

Sodium homeostasis and hormonal responses during dopaminergic blockade in normal humans.

Six normal subjects were submitted to 2 h water immersion (WI) with and without pharmacological dopaminergic (DA) blockade with metoclopramide (MCP). Urinary sodium excretion showed a marked increase during WI alone while it was blunted during WI plus DA blockade. Plasma aldosterone was significantly suppressed by WI alone but remained unchanged during WI plus MCP. Plasma atrial natriuretic factor showed similar augmentation during WI alone and during WI plus MCP. The reduced sodium and 6-keto-PGF1 alpha excretion, observed during WI plus MCP administration, suggests that dopamine might induce prostacyclin synthesis in the kidney during WI.

Dopaminergic modulation of acute renal effects of nicardipine.

In order to investigate whether dopamine receptors are involved in the acute natriuretic effects of calcium channel blockade, experiments were carried out in humans with uncomplicated essential hypertension. In 8 hypertensives 5 mg intravenous nicardipine produced a large decrease in blood pressure and renal vascular resistance, a slight but significant increase in glomerular filtration rate (GFR) and marked natriuresis. When a second identical experiment was performed in the same subjects with the addition of 10 mg metoclopramide as dopamine blocker, changes in sodium excretion and vascular resistance were the same, but GFR did not increase during nicardipine. In a second set of experiments (n = 5) the same design was used, but nicardipine was infused at a dose of 0.01 mg/kg, ie, seven times less than in previous experiments. Under these conditions, blood pressure, renal vascular resistance and GFR did not change, but significant natriuresis occurred. Natriuresis was almost completely prevented by metoclopramide. In 5 additional hypertensives, metoclopramide alone was infused and 0.01 mg/kg nicardipine was added to the infusion. No change in any parameter was observed. Our findings suggest that the dopaminergic system participates in maintaining or increasing GFR during blood pressure reduction by calcium antagonists, although renal vasodilation and natriuresis are largely independent of dopamine receptor activity. In addition, when low doses of calcium antagonists produce natriuresis in the absence of renal or systemic hemodynamic changes (direct tubular effect), dopamine blockade is able to blunt this effect. This indicates a modulation by dopaminergic receptors of the direct tubular action of calcium antagonists.

A new diagnostic test for primary aldosteronism.

Isotonic-isooncotic central volume expansion by head-out water immersion was induced in six aldosterone-producing adenoma subjects and in six patients with idiopathic hyperaldosteronism. Plasma renin activity and plasma aldosterone levels did not significantly change during water immersion while serum cortisol was significantly suppressed (P less than .001) and the aldosterone-cortisol ratio increased (P less than .02) in aldosterone-producing adenoma patients. Water immersion also revealed the failure of plasma aldosterone levels to decrease below 10 ng/dL in these subjects, thus confirming previous results obtained during isotonic saline infusion. Otherwise, plasma renin activity and plasma aldosterone were significantly reduced (P less than .05 and P less than .01 respectively) by water immersion and plasma aldosterone invariably fell below 10 ng/dL in patients with idiopathic aldosteronism. In view of the diagnostic reliability of such a suppression test we conclude that water immersion is suitable for discriminating between the two forms of primary aldosteronism. We therefore suggest its use for assessing renin-aldosterone responsiveness in primary aldosteronism.

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.

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.

Renin-angiotensin system unresponsiveness in phaeochromocytoma.

Water immersion to the neck is able to provoke a profound suppression of the renin-angiotensin system in several clinical conditions associated with hyper-reninaemia. Both hyper-reninaemia and secondary aldosteronism have sometimes been described in phaeochromocytoma. We report on two patients, with surgically proven phaeochromocytoma, in whom water immersion, performed before surgery, failed to induce any significant change in plasma renin activity.

The renin-aldosterone system and renal function in kidney transplantation.

Six renal transplant recipients, six uninephrectomized patients and six normal subjects were subjected to the physiological manoeuvre of head-out water immersion (WI), in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. The denervated, transplanted kidneys of the six patients were able to maintain a sodium excretory response to WI identical to that obtained in the controls (from 121 +/- 18 to 236 +/- 29 mumol/min, p < 0.005 vs 113 +/- 17 to 213 +/- 18 mumol/min, p < 0.005, respectively). Kidney transplant patients were also characterized by a preserved suppression of renin-aldosterone system (from 1.2 +/- 0.2 to 0.5 +/- 0.1 ng/ml/h, p < 0.03 and 12 +/- 1.0 to 7.0 +/- 1.0 ng/dl, p < 0.005, respectively) and stimulation of atrial natriuretic peptide (from 84 +/- 15 to 153 +/- 25 pg/ml, p < 0.05) to central hypervolemia by water immersion. The present study, while confirming the ability of the denervated kidney to handle sodium normally, also suggests that atrial natriuretic peptide could assume a crucial role in regulating renin secretion.

[Paraneoplastic polymyalgia rheumatica. Case contribution]. / La polimialgia reumatica paraneoplastica. Contributo casistico.

Polymyalgia rheumatica (PMR) is an inflammatory disease which mainly affects the elderly and is highly responsive to steroid therapy. PMR can be associated with giant cell arteritis as well as with malignancy. Three cases of malignant neoplasms of the digestive apparatus beginning with a clinical picture similar to that of the "idiopathic" PMR, but with poor response to steroid therapy are presented. In one case the primary neoplasm was found only at the autopsy. These observations suggest that a careful clinical evaluation and a long follow-up are necessary for a correct diagnosis of "idiopathic" PMR.

[Notes on a case of clinostatic chyluria]. / Note su un caso di chiluria clinostatica

A clinical case of clinostatic chyluria of unknown non-parasitic aetiology, is reported. Ascending pyelography showed the presence of lymphatic communications between right renal pelvis and homolateral lumbo-aortic lymph nodes. Aetiology, pathogenesis, prognosis and diagnostic tools of use in the syndrome are discussed. The problem of the possible lymphatic origin of benign proteinuria, in relation to anatomic considerations and to quality and quantity resemblances between individual protein fractions in chyluria and benign proteinuria encountered in the present case, is also discussed. In order to clarify the problem, emphasis is laid on the advisability of simultaneously studying urinary protein composition in postural chyluria and lipid composition in benign proteinuria.

[Drug therapy of pheochromocytoma]. / Terapia medica del feocromocitoma.

The Authors briefly review the clinical findings, the diagnostic biochemical procedures and the management of pheochromocytoma. The most recent pharmacological approaches with calcium-channel blockers or angiotensin-converting enzyme inhibitors are particularly discussed.

[Antihypertensive treatment: a combination of delapril, a new ACE-inhibitor, and indapamide]. / Terapia antipertensiva: associazione tra delapril, nuovo ACE-inibitore, ed indapamide.

The controlled study was carried out on 15 patients with essential hypertension not sufficiently controlled after one month of monotherapy with an ACE-inhibitor. To the above therapy was therefore associated a low dosage diuretic (indapamide 2.5 mg/day). The observation period was of 12 weeks. The delapril-indapamide combination was found to be very effective in reducing blood pressure values; no significant metabolic adverse effects were observed.