Guido O. Perez

Aortic Pressure Augmentation Predicts Adverse Cardiovascular Events in Patients With Established Coronary Artery Disease

Pulse pressure (PP), a marker of arterial stiffness, predicts cardiovascular risk. We aimed to determine whether augmentation pressure (AP) derived from the aortic pressure waveform predicts major adverse cardiovascular events (MACE) and death independently of PP in patients with established coronary artery disease (CAD). We prospectively followed-up 297 males undergoing coronary angiography for 1186±424 days. Ascending aortic pressure tracings obtained during catheterization were used to calculate AP (difference between the second and the first systolic peak). Augmentation index (AIx) was defined as AP as a percentage of PP. We evaluated whether AP and AIx can predict the risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke, or death) and death using Cox regression. All models evaluating AP included PP to assess whether AP adds to the information already provided by PP. Both AP and AIx significantly predicted MACE. The hazard ratio (HR) per 10 mm Hg increase in AP was 1.20 (95% confidence interval [CI], 1.08 to 1.34; P<0.001); the HR for each 10% increase in AIx was 1.28 (95% CI, 1.11 to 1.48; P=0.004). After adjusting for other univariate predictors of MACE, age, and other potential confounders, AP remained a significant predictor of MACE (HR per 10 mm Hg increase=1.19; 95% CI, 1.06 to 1.34; P=0.002), as did AIx (adjusted HR, 1.28; 95% CI, 1.09 to 1.50; P=0.003). AP was a significant predictor of death (HR per 10 mm Hg increase=1.18; 95% CI, 1.02 to 1.39; P=0.03). Higher AIx was associated with a trend toward increased mortality (HR=1.22; 95% CI, 0.98 to 1.52; P=0.056). Aortic AP predicts adverse outcomes in patients with CAD independently of PP and other risk markers.

Serum Potassium Concentration in Acidemic States

It has been generally accepted that acidosis results in hyperkalemia because of shifts of potassium from the intracellular to the extracellular compartment. There is ample clinical and experimental evidence, however, to support the conclusion that uncomplicated organic acidemias do not produce hyperkalemia. In acidosis associated with mineral acids (respiratory acidosis, end-stage uremic acidosis, NH4Cl-or CaCl2-induced acidosis), acidemia per se, results in predictable increases in serum potassium concentration. In acidosis associated with nonmineral organic acids (diabetic and alcoholic acidosis, lactic acidosis, methanol and the less common forms of organic acidemias secondary to methylmalonic and isovaleric acids, and ethylene glycol, paraldehyde and salicylate intoxications), serum potassium concentration usually remains within the normal range in uncomplicated cases. A number of factors, however, may be responsible for hyperkalemia in some of these patients other than the acidemia per se. These include dehydration and renal hypoperfusion, preexisting renal disease, hypercatabolism, diabetes mellitus, hypoaldosteronism, the status of potassium balance, and therapy. The mechanism(s) of this differing effect of mineral and organic acidemias on transmembrane movement of potassium remains undefined. The prevalent hypothesis, however, favors the free penetrance of the organic anion into cells without creating a gradient for the hydrogen ions and, thus, obviating the efflux of intracellular potassium. The importance of the presence of hyperkalemia in clinical states of organic acidemias is obvious. A search for the complicating factors reviewed above should be undertaken since organic acidemias per se, should not be expected to be accompanied by elevations of serum potassium concentration. Moreover, the classical teaching that the absence of hyperkalemia during severe acidosis is indicative of severe potassium deficiency, may not be universally valid in patients with uncomplicated organic acidemias.

Renal acidosis and renal potassium handling in selective hypoaldosteronism

Abstract Selective hypoaldosteronism was demonstrated in a 60 year old black man with moderate renal insufficiency and hyperkalemic, hyperchloremic acidosis. Urine pH was appropriately low during acid loading demonstrating that the hydrogen ion gradient generating capability of the distal-most nephron was intact. In addition to impaired net acid excretion during acidosis, significant bicarbonaturia was present when serum bicarbonate concentration was normal. Desoxycorticosterone acetate (DOCA) administration improved renal potassium handling and corrected the hyperkalemia but not the acidosis or bicarbonaturia. It is concluded that the patient had idiopathic selective hypoaldosteronism and hyporeninemia and that the hyperkalemia was related to hypoaldosteronism. The patients bicarbonaturia, however, did not appear to be related to mineralocorticoid deficiency and therefore should be attributed to other factors.

Interaction of Cyclosporine A and Nonsteroidal Anti-inflammatory Drugs on Renal Function in Patients With Rheumatoid Arthritis

PURPOSE To determine the additive renal effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclosporine A (CYA) in patients with rheumatoid arthritis (RA) and to determine the effects of CYA on active RA. PATIENTS AND METHODS Eleven patients with RA refractory to other agents were treated separately for 2-week periods with an NSAID (sulindac or naproxen), CYA (5 mg/kg/d), and NSAID plus CYA in combination (NSAID/CYA). The NSAID/CYA combination was continued for an additional 20 weeks. Clinical parameters of RA, electrolytes, renal function, and the renin-aldosterone system were evaluated at each interval to determine the potential interaction of these two agents. RESULTS Combined therapy was effective in suppressing many measures of active RA in 9 of the 11 patients. Adverse drug reactions were common, but withdrawals were limited to hirsutism (one) and peripheral neuropathy (one). In about half of the patients, CYA or NSAID resulted in a decrease in the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), with a mild reduction in the filtration fraction. With NSAID or CYA, early morning renin-aldosterone system values were mildly suppressed, and their response to ambulation/intravenous (IV) furosemide was not blunted. When combined, NSAID/CYA caused more marked reductions of GFR and ERPF at 2 weeks, and this persisted at 20 weeks. The morning renin-aldosterone system values during administration of NSAID/CYA were suppressed, with an added blunted response to ambulation/IV furosemide. CONCLUSION As previously suspected, the impairment of renal function when CYA and NSAID are combined is greater than that obtained with either agent alone. This hemodynamic effect was reversible and appeared to be, at least in part, due to renal vasoconstriction.

Human Immunodeficiency Virus and Human T-Cell Leukemia Virus Type I in Patients Undergoing Maintenance Hemodialysis in Miami

The high prevalence of human immunodeficiency virus (HIV-1) infection in populations at risk in Miami prompted a seroepidemiologic study of both HIV-1 and the human T-cell leukemia virus type I (HTLV-I), a closely related virus, in our patients receiving chronic hemodialysis. One hundred twenty-nine patients undergoing hemodialysis in 1986 and 1987 were tested for antibody against both viral antigens by EIA (Abbott Laboratories, Abbott Park, IL). Seroreactive samples for HIV-1 and/or HTLV-I were confirmed by Western blot and, for HTLV-I, by viral cultures. Thirty patients (23.2%) were positive for retroviral infection (22 for HIV-1 alone, four for HTLV-I alone, and four for both HIV-1 and HTLV-I). The most important risk factor was intravenous drug use, followed by blood transfusion. Patients with HIV-1 had lower T4-T8 ratios and higher mortality than those with HTLV-I infection alone. It was concluded that HTLV-I, as well as HIV-1, infection is endemic in chronic dialysis centers in Miami. The clinical consequences of HTLV-I infection in relatively immunocompromised patients with chronic uremia who are undergoing chronic hemodialysis remains to be established.

Effects of hemodialysis on left ventricular diastolic filling.

Diastolic Doppler filling parameters were measured before and after hemodialyses, performed once with and once without fluid removal. Changes occurred only with fluid removal and correlated with weight loss, indicating that they are the result of reduction in preload.

Fatal Destructive Cervical Spondyloarthropathy in Two Patients on Long-Term Dialysis

Two patients with fatal cervical cord compressive myelopathy are described, both of whom had been on dialysis for more than 15 years. Destructive changes were noted in mid and upper cervical regions, with soft tissue mass in the atlanto-occipital region in one patient. Clinical and radiographic findings suggest both amyloid and hyperparathyroidism as possible etiologies for these destructive spinal changes. Clinicians should be aware that the full picture of quadriparesis may be associated with destructive spondyloarthropathy (DSA) in long-term dialysis patients.

The biosynthesis of guanidinosuccinic acid by perfused rat liver.

The metabolic pathway for the synthesis of guanidinosuccinic acid was studied in the rat. Labeled guanidinosuccinic acid was isolated from the urine of animals given L-[guanidino-14C]arginine intraperitoneally but did not appear in the urine after administration of D,L-[guanidino-14C]canavanine. Radioactive arginine and nonradioactive aspartic acid and arginine were infused in the isolated, perfused rat liver. After 20 min, small amounts of both labeled and unlabeled guanidinosuccinic acid and large amounts of urea were detected in radiochromatograms of the perfusate. These results support the theory that guanidinosuccinic acid is formed in the liver from transamidination of arginine to aspartic acid.

Pharmacokinetics of ranitidine in patients with renal failure

The pharmacokinetics of ranitidine were studied in ten patients with renal failure (creatinine clearance, 6–54 mL/min) after intravenous (IV) (50 mg) and oral doses (150 mg). After oral administration, peak plasma concentrations of 378–808 ng/mL were obtained in two to six hours. Plasma concentrations declined very slowly and concentrations greater than 100 ng/mL were obtained for 16 to 20 hours after the dose. The elimination half‐life following oral administration was 8.5 ± 2.8 hours (standard deviation [SD]), and the bioavailability of ranitidine was 43.3% ± 10.5%. After IV administration, the elimination half‐life, plasma clearance, renal clearance, and volume of distribution were 7.0 ± 1.0 hours, 170 ± 38 mL/min, 36.0 ± 25.0 mL/min, and 1.3 ± 0.4 L/kg, respectively. About 20% of the IV dose and 9% of the oral dose were recovered unchanged in urine. There was a significant correlation between the renal clearance of ranitidine and creatinine clearance (r = .74, P < .05) after IV administration. The elimination half‐life in patients with renal insufficiency is about three times greater than that reported in the literature for healthy subjects. Similarly, the plasma clearance in these patients is about 20% of that reported in healthy subjects. The results indicate that ranitidine elimination is appreciably reduced in renal failure and that an adjustment of dose in patients with renal failure is warranted. A dose of 75 mg bid may be adequate in maintaining the therapeutic plasma concentrations that are required for adequate H2‐blocking activity.

Serum levels of high-density lipoprotein phospholipids correlate inversely with severity of angiographically defined coronary artery disease

In an attempt to assess the relationship between lipid abnormalities and severity of coronary artery disease, we measured serum levels of cholesterol (SC), triglycerides (TG), phospholipids (SP), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), and high density lipoprotein phospholipids (HDL-P), in 217 men undergoing diagnostic coronary arteriography. We found significantly higher mean values of HDL-P and HDL-C in men with normal coronaries, but no significant differences in the other measured lipids. While there was no significant difference in HDL-C among patients with one, two or three-vessel disease, there was a negative correlation between HDL-P levels and the severity of the disease. These observations suggest that prospective studies would be of merit to establish the relevance of HDL-P in the development of coronary artery disease.