Trends and outcomes of opioid-related cardiac arrest in a contemporary US population

Background: Opioid abuse is a worldwide public health issue, and deaths related to opioid abuse are increasing. We aimed to investigate trends, predictors, and outcomes of cardiac arrest in patients with opioid abuse. Methods: All hospitalizations for primary diagnosis of cardiac arrest between 2012 and 2018 identified in the Nationwide Inpatient Sample were categorized into those with or without a secondary diagnosis of opioid overdose. Multivariable logistic regression was used to analyze in-hospital outcomes of opioid-associated cardiac arrest after adjusting for patient and hospital characteristics. Results: Among 1,410,475 hospitalizations with cardiac arrest, opiate abuse as a secondary diagnosis was found in 3.1% (n=43,090) of hospitalizations, with an increasing trend during the study period. Hospitalizations for cardiac arrest with opioid abuse were seen less likely in patients with heart failure (21.2% vs. 40.6%; p<0.05), diabetes mellitus (19.5% vs. 35.4%; p<0.05), hypertension (43.4% vs. 64.9%; p<0.05) and renal failure (14.3% vs. 30.2%; p<0.05) and more frequently in those with history of alcohol abuse (16.9% vs. 7.1%; p<0.05), depression (18.8% vs. 9%; p<0.05), and smoking (37.0% vs. 21.8%; p<0.05) as compared with cardiac arrest without opioid use. In-hospital mortality in cardiac arrest patients with and without opioids was not different after multivariable adjustment (odds ratio OR 0.96, 0.91-1.00; p=0.07). OA-OHCA was associated with significantly higher risks of acute kidney injury, acute respiratory failure, and mechanical ventilation, p<0.05 for all. Conclusion: Opioid abuse remains a significant cause of cardiac arrest. Despite similar in-hospital mortality and lower resource utilization, severe complications are more frequent in opioid abuse related cardiac arrests compared to those without opioid abuse. © 2021 European Federation of Internal Medicin

Increased Vascular α1-adrenergic Sensitivity In Patients With Renal Failure: Receiving Recombinant Erythropoeitin

End stage renal disease (ESRD) is associated with altered hemodynamic regulation as a result of the pathophysiology or treatment of renal failure. Hypertension, common among dialysis patients, is a recognized complication of recombinant human erythropoietin (rHuEPO) therapy. We determined vascular adrenergic and nitric-oxide-mediated responsiveness in 7 patients with established ESRD on rHuEPO treatment and in 13 healthy volunteers using the dorsal hand vein technique. Sensitivity to the α1-adrenergic selective agonist phenylephrine was significantly increased in patients with ESRD on rHuEPO. The mean dose of phenylephrine producing 50% venoconstriction (ED50) was 38 ± 1.6 ng/min in patients with ESRD and 135 ± 1.3 ng/min in healthy volunteers-almost a 4-fold increase in dose, P = 0.01. In contrast, maximal venodilation mediated by bradykinin, an endothelium-dependent vasodilator, was not different in the 2 groups. To determine whether rHuEPO has a direct vasoconstrictor effect, we studied venous responsiveness to local infusions of rHuEPO in healthy volunteers. Increasing concentrations of rHuEPO produced no vasoconstriction in hand veins of healthy volunteers. These results suggest that vascular responsiveness to α-adrenergic stimulation in patients with ESRD on rHuEPO is increased whereas bradykinin-mediated venodilation remains intact. This increase in vascular α-adrenergic responsiveness may contribute to the increased peripheral vascular resistance and hypertension seen in patients with ESRD on rHuEPO. © 2007 Lippincott Williams & Wilkins, Inc.145427434Eschbach, J., Egrie, J., Downing, M., Correction of the anemia of ESRD with recombinant human erythropoietin. 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genetically hypertensive rats (1993) Life Sci, 52, pp. 1425-1434Neusser, M., Tepel, M., Zidek, W., Erythropoietin increases cytosolic free calcium concentration in vascular smooth muscle cells (1993) Cardiovasc Res, 27, pp. 1233-1236Bund, S., Heagerty, A., Edmunds, M., Erythropoietin does not induce vasoconstriction directly in human subcutaneous resistance arterioles (1989) Nephron, 53, p. 173Pagel, H., Jelkmann, W., Weiss, C., Erythropoietin and blood pressure (1989) Horm Metab Res, 21, p. 224Lai, K.N., Lui, S.F., Leung, J.C., Effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin on blood pressure and vasoactive hormones in patients on continuous ambulatory peritoneal dialysis (1991) Nephron, 57, pp. 394-400Yaqoob, M., Morris, K., Bell, G., Suppression of the renin-angiotensin-aldosterone axis with erythropoietin therapy by a negative feedback loop (1992) Nephrol Dial Transplant, 7, pp. 125-128Lebel, M., Kingma, I., Grose, J.H., Hemodynamic and hormonal changes during erythropoietin treatment in hemodialysis patients (1998) J Am Soc Nephrol, 9, pp. 97-104Hand, M., Haynes, W., Johnstone, H., Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure (1995) Kidney Int, 48, pp. 806-813Bode-Boger, S., Boger, R., Kuhn, M., Recombinant human erythropoietin enhance vasoconstriction tone via endothelin-1 and constrictor prostanoids (1996) Kidney Int, 50, pp. 1255-1261Zhou, X.J., Pandian, D., Wang, X.Q., Erythropoietin-induced hypertension in rats is not mediated by alterations of plasma endothelin, vasopressin, or atrial natriuretic peptide levels (1997) J Am Soc Nephrol, 8, pp. 901-905Vallance, P., Leone, A., Calver, A., Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure (1992) Lancet, 339, pp. 572-575Dachman, W., Ford, G., Blaschke, T., Mechanism of bradykinin-induced venodilation in humans (1993) J Cardiovasc Pharmacol, 21, pp. 241-248Calver, A., Collier, J., Leone, A., Effect of local intraarterial asymmetric dimethylarginine (ADMA) on the forearm arteriolar bed of healthy volunteers (1993) J Hum Hypertens, 7, pp. 193-194Pan, H., Hoffman, B., Pershe, R., Decline in beta adrenergic receptor-mediated relaxation with aging in man (1986) J Pharmacol Exp Ther, 239, pp. 802-807Fleming, W., Westfall, D., De La Lande, I., Log-normal distribution of effective doses of norepinephrine and acetylcholine in several tissues (1972) J Pharmacol Exp Ther, 181, pp. 339-345Warren, D., Mathias, C., Naik, R., Hemodynamic effects of noradrenaline and isoprenaline in chronic renal failure (1984) Contr Nephrol, 41, pp. 420-424Pan, H., Hoffman, B., Persche, R., Differences in recovery from vasoconstriction due to alpha agonists studiedwith the dorsal hand vein technique (1985) Clin Pharmacol Ther, 37, p. 219Alradi, A., Carruthers, S., Evaluation and application of the linear variable differential transformer technique for the assessment of human dorsal vein alpha receptor activity (1985) Clin Pharmacol Ther, 38, pp. 495-502Bauersachs, J., Popp, R., Hecker, M., Nitric oxide attenuates the release of endothelium-derived hyperpolarizing factor (1996) Circulation, 94, pp. 3341-3347McCulloch, A.I., Bottrill, F.E., Randall, M.D., Characterization and modulation of EDHF-mediated relaxations in the rat isolated superior mesenteric arterial bed (1997) Br J Pharmacol, 120, pp. 1431-1438Taddei, S., Ghiadoni, L., Virdis, A., Vasodilation to Bradykinin is mediated by an Oubain-sensitive pathway as a compensatory mechanism for impaired Nitric oxide availability in essential hypertensive patients (1999) Circulation, 100, pp. 1400-1405Quilley, J., Fulton, D., McGiff, J.C., Hyperpolarizing factors (1997) Biochem Pharmacol, 54, pp. 1059-1070Ford, G., Katzir, D., Blaschke, T., Responsiveness of peripheral veins to vasodilators and the effect of nifedipine on alpha adrenergic responsiveness in hypertension (1991) Clin Pharmacol Ther, 50, p. 198Eichler, H., Ford, G., Blaschke, T., Responsiveness of superficial hand veins to phenylephrine in essential hypertension (1989) J Clin Invest, 83, pp. 108-112Feldman, R., Freedman, D., Bierbrier, G., Beta adrenergic responsiveness is regulated selectively in hypertension (1993) Clin Pharmacol Ther, 54, pp. 654-66

Effect of serum Insulin on the association between hyperuricemia and incident heart failure

Increased serum uric acid (UA) is associated with incident heart failure (HF). However, whether it is a direct effect of UA or an effect of increased xanthine oxidase (XO) is unknown. Because hyperuricemia in hyperinsulinemia is primarily due to impaired renal UA excretion, its association with incident HF would suggest a direct UA effect. In contrast, hyperuricemia in normoinsulinemia is likely due to increased UA production and thus its association with incident HF would suggest an XO effect. To clarify this, we examined the association of hyperuricemia with centrally adjudicated incident HF in Cardiovascular Health Study participants with and without hyperinsulinemia. Of the 5,411 participants <65 years of age without baseline HF, 1,491 (28%) had hyperuricemia (serum UA <6 mg/dl for women and <7 mg/dl for men). Propensity scores for hyperuricemia were estimated using 63 baseline characteristics. Mean serum UA levels were 6.0 and 5.3 mg/dl in those with (n = 2,731) and those without (n = 2,680) hyperinsulinemia (median serum insulin <13 mU/L), respectively (p <0.001). Propensity-adjusted hazard ratios (95% confidence intervals) for hyperuricemia-associated incident HF during 8 years of median follow-up were 0.99 (0.83 to 1.18, p = 0.886) and 1.32 (1.04 to 1.67, p = 0.021) for those with and without hyperinsulinemia respectively (p for interaction = 0.014). In conclusion, the absence of an association of hyperuricemia with incident HF in those with hyperinsulinemia (despite a significantly higher mean serum UA) and a significant association in normoinsulinemia suggest that UA has no intrinsic association with incident HF and that it may predict incident HF when it is a marker of increased of XO activity. © 2010 Elsevier Inc. All rights reserved

Uncontrolled hypertension and increased risk for incident heart failure in older adults with hypertension: findings from a propensity-matched prospective population study

Hypertension is a risk factor for incident heart failure (HF). However, the effect of uncontrolled blood pressure (BP) on incident HF in older adults with hypertension has not been prospectively examined in propensity-matched studies. Of the 5795 Cardiovascular Health Study participants, ≥65 years, 2562 with self-reported physician-diagnosed hypertension had no baseline HF. Of these, 1391 had uncontrolled hypertension, defined as systolic BP (SBP) ≥140 (n = 1373) or diastolic BP ≥90 mm Hg (n = 18). Propensity scores for uncontrolled hypertension, calculated for each participant, were used to assemble a cohort of 1021 pairs of participants with controlled and uncontrolled hypertension who were balanced on 31 baseline characteristics. Centrally adjudicated incident HF developed in 23% and 26% of participants with controlled and uncontrolled hypertension respectively during 13 years of follow-up (matched hazard ratio [HR] when uncontrolled hypertension was compared with controlled hypertension, 1.39; 95% confidence interval [CI], 1.12 to 1.73; P = .003). HRs (95% CI) for incident HF for those with (n = 503) and without (n = 1539) chronic kidney disease (CKD) were 1.73 (95% CI, 1.26 to 2.38; P = .001) and 1.08 (95% CI, 0.87 to 1.34; P = .486) respectively (P for interaction, .012). Compared with participants with controlled hypertension, HRs for incident HF associated with SBP 140 to 159 and ≥160 mm Hg were 1.06 (95% CI, 0.86 to 1.31; P = .572) and 1.58 (95% CI, 1.27 to 1.96; P < .0001), respectively. In community-dwelling older adults with hypertension, those with uncontrolled (versus controlled) BP have increased risk of new-onset HF, which is more pronounced in those with SBP ≥160 mm Hg and with CKD

Long-term treatment with the apolipoprotein A1 mimetic peptide increases antioxidants and vascular repair in type I diabetic rats

Apolipoprotein A1 mimetic peptide (D-4F), synthesized from D-amino acid, enhances the ability of high-density lipoprotein to protect low-density lipoprotein (LDL) against oxidation in atherosclerotic disease. Using a rat model of type I diabetes, we investigated whether chronic use of D-4F would lead to up-regulation of heme oxygenase (HO)-1, endothelial cell marker (CD31(+)), and thrombomodulin (TM) expression and increase the number of endothelial progenitor cells (EPCs). Sprague-Dawley rats were rendered diabetic with streptozotocin (STZ) and either D-4F or vehicle was administered, by i.p. injection, daily for 6 weeks (100 microg/100 g b.wt.). HO activity was measured in liver, kidney, heart, and aorta. After 6 weeks of D-4F treatment, HO activity significantly increased in the heart and aorta by 29 and 31% (p < 0.05 and p < 0.49), respectively. Long-term D-4F treatment also caused a significant increase in TM and CD31(+) expression. D-4F administration increased antioxidant capacity, as reflected by the decrease in oxidized protein and oxidized LDL, and enhanced EPC function and/or repair, as evidenced by the increase in EPC endothelial nitric-oxide synthase (eNOS) and prevention of vascular TM and CD31(+) loss. In conclusion, HO-1 and eNOS are relevant targets for D-4F and may contribute to the D-4F-mediated increase in TM and CD31(+), the antioxidant and anti-inflammatory properties, and confers robust vascular protection in this animal model of type 1 diabetes