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Background— Temporal trends and contemporary data characterizing the impact of patient age on in-hospital outcomes of percutaneous coronary interventions are lacking. We sought to determine the importance of age by assessing the in-hospital mortality of stratified age groups in the National Cardiovascular Data Registry. Methods and Results— In-hospital mortality after percutaneous coronary intervention on 1 410 069 patients was age stratified into 4 groups—group 1 (age <40, n=25 679), group 2 (40 to 59, n=496 204), group 3 (60 to 79, n=732 574), and group 4 (≥80, n=155 612)—admitted from January 1, 2001, to December 31, 2006. Overall in-hospital mortality was 1.22%; in-hospital mortality was 0.60%, 0.59%, 1.26%, and 3.16% in groups 1 to 4, respectively, P <0.0001. Overall temporal improvement per calendar year in the adjusted in-hospital mortality after percutaneous coronary intervention was noted in most groups; however, this finding was significant only in the 2 older age groups, group 3 (odds ratio, 0.94; 95% CI, 0.92 to 0.96) and group 4 (odds ratio, 0.95; 95% CI, 0.92 to 0.97). The absolute mortality reduction was greatest in the most elderly group, those over the age of 80 years. Conclusions— In-hospital mortality after percutaneous coronary intervention has fallen for all age groups over the past 6 years. However, the largest absolute reduction was seen among patients 80 years of age or older.

OBJECTIVE—To determine the contribution of liver and viscera to splanchnic cortisol production in humans. RESEARCH DESIGN AND METHODS—D4 cortisol was infused intravenously; arterial, portal venous, and hepatic venous blood was sampled; and liver and visceral fat were biopsied in subjects undergoing bariatric surgery. RESULTS—Ratios of arterial and portal vein D4 cortisol/cortisoltotal (0.06 ± 0.01 vs. 0.06 ± 0.01) and D4 cortisol/D3 cortisol (1.80 ± 0.14 vs. 1.84 ± 0.14) did not differ, indicating that no visceral cortisol production or conversion of D4 cortisol to D3 cortisol via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) occurred. Conversely, ratios of both D4 cortisol to cortisoltotal (0.05 ± 0.01; P &lt; 0.05) and D4 cortisol to D3 cortisol (1.33 ± 0.11; P &lt; 0.001) were lower in the hepatic vein than in the portal vein, indicating production of both cortisol and D3 cortisol by the liver. The viscera did not produce either cortisol (−8.1 ± 2.6 μg/min) or D3 cortisol (−0.2 ± 0.1 μg/min). In contrast, the liver produced both cortisol (22.7 ± 3.90 μg/min) and D3 cortisol (1.9 ± 0.4 μg/min) and accounted for all splanchnic cortisol and D3 cortisol production. Additionally, 11β-HSD-1 mRNA was approximately ninefold higher (P &lt; 0.01) in liver than in visceral fat. Although 11β-HSD-2 gene expression was very low in visceral fat, the viscera released cortisone (P &lt; 0.001) and D3 cortisone (P &lt; 0.01) into the portal vein. CONCLUSIONS—The liver accounts for all splanchnic cortisol production in obese nondiabetic humans. In contrast, the viscera releases cortisone into the portal vein, thereby providing substrate for intrahepatic cortisol production.

The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11β-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11β-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11β-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13BN rats. Knockdown of renal medullary 11β-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11β-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11β-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

Background— We sought to validate the recently developed Mayo Clinic Risk Score model for in-hospital mortality after percutaneous coronary intervention using an independent data set. The Mayo Clinic Risk Score has 7 simple clinical and noninvasive variables, available before coronary angiography, for prediction of in-hospital mortality. External validation using an independent data set would support broader applicability of the model. Methods and Results— In-hospital mortality after percutaneous coronary intervention on 309 351 patients from the National Cardiovascular Data Registry admitted from January 1, 2004, to March, 30, 2006, was studied. Using the Mayo Clinic Risk Score equation, we assigned predicted probabilities of death to each patient. The area under the receiver-operating characteristics curve was 0.884, indicating excellent discrimination overall as well as among subgroups, including gender, diabetes mellitus, renal failure, low ejection fraction, different age groups, and multivessel disease. Ninety-seven percent of patients undergoing percutaneous coronary intervention had a Mayo Clinic Risk Score <10, indicating low to intermediate risk. The Mayo Clinic Risk Score model initially slightly underpredicted event rates when applied in National Cardiovascular Data Registry data (observed 1.23% versus predicted 1.10%), but this underprediction was corrected after recalibration. The recalibrated risk score discriminated (c index=0.885) and calibrated well in an National Cardiovascular Data Registry validation data set consisting of procedures performed between April 1, 2006, and March 30, 2007. Conclusions— Seven variables can be combined into a convenient risk scoring system before coronary angiography is performed to predict in-hospital mortality after percutaneous coronary intervention. This model may be useful for providing patients with individualized, evidence-based estimates of procedural risk as part of the informed consent process before percutaneous coronary intervention.

Background— Myonecrosis after percutaneous coronary intervention (PCI) has been correlated with a worse prognosis, but controversy exists about the clinical significance and potential mechanisms for the association. The aim of this study was to evaluate the relative impact of preprocedural and postprocedural cardiac troponin T (cTnT) levels on survival rate after PCI. Methods and Results— We evaluated 5487 patients from the Mayo Clinic registry who required nonemergency PCI, and we examined the relationship between periprocedural cTnT levels, with the 99th percentile cutoff value used for normal (<0.01 ng/mL), and outcomes. The patients were divided into 3 groups: normal preprocedural and postprocedural cTnT levels (no myonecrosis), normal preprocedural but elevated postprocedural cTnT levels (PCI-related myonecrosis), and abnormal preprocedural cTnT. The 30-day death rates were 0.1%, 0.6%, and 2.3%, respectively, in the 3 groups. In a multivariable model, an abnormal pre-PCI cTnT level (hazard ratio 9.66 [2.30–40.57]; P =0.002), and PCI-related myonecrosis (4.71 [1.02–21.83]; P =0.048) were independent predictors of 30-day mortality. Over a median follow-up of 28 months, an abnormal pre-PCI cTnT level (hazard ratio 1.79 [1.35–2.39]; P <0.001) independently predicted death, but the occurrence of PCI-related myonecrosis did not. A postprocedural elevation in creatine kinase MB fraction was not an independent predictor of long-term risk of death (0.912 [0.70–1.19]; P =0.5). Conclusions— A preprocedural cTnT level >0.01 is a powerful independent predictor of prognosis after PCI and is of greater prognostic significance than the postprocedural biomarker levels. PCI-related myonecrosis occurs frequently and predicts short-term but not long-term risk of death.

The feasibility and clinical utility of early electroencephalogram (within 48 hours) was studied in 127 children (age, 1 month-17 years) referred for a “first seizure.” The electroencephalogram was considered late after 48 hours. Electroencephalogram abnormalities were classified as nonepileptiform or epileptiform. Children were classified as having an “epileptic” or “nonepileptic” event. An early electroencephalogram was obtained in 23 (18%). Late referral (n = 36), weekend event (n = 23), difficulty contacting families (n = 11), parental schedules (n = 9), and laboratory scheduling (n = 11) resulted in late electroencephalograms. All 94 children with an epileptic event had an electroencephalogram, 19 (20%) within 48 hours. Results were abnormal in 9 (47%) early (7 epileptiform, 2 nonepileptiform) and 35 (44%) late (30 epileptiform, 5 nonepileptiform). Increased abnormalities were not seen with early electroencephalography ( P = .50). Early electroencephalograms may not be feasible in the pediatric population and did not show a higher yield of abnormalities.

Abstract Background: The accurate and precise measurement of urinary albumin is critical, since even minor increases are diagnostically sensitive indicators of renal disease, cardiovascular events, and risk for death. To gain insights into potential measurement biases, we systematically compared urine albumin measurements performed by LC-MS, a clinically available immunoturbidimetric assay, and size-exclusion HPLC. Methods: We obtained unused clinical urine samples from 150 patients who were stratified by degrees of albuminuria (&lt;20 mg/L, 20–250 mg/L, &gt;250 mg/L) as determined by the immunoturbidimetric assay used in our clinical laboratory (Roche Hitachi 912). Urine albumin was then remeasured via LC-MS and HPLC (Accumin™) assays. Results: The immunoturbidimetric assay, calibrated using manufacturer-supplied serum-derived calibrators (Diasorin), underestimated albumin compared with LC-MS. After calibration with purified HSA, this immunoturbidimetric assay correlated well with LC-MS. HPLC overestimated albumin compared with both LC-MS and immunoturbidimetry. The current LC-MS and HPLC assays both performed poorly at concentrations &lt;20 mg/L. Conclusions: Efforts are needed to establish gold-standard traceable calibrators for clinical assays. LC-MS is a specific method to quantify albumin in native urine when concentrations exceed 20 mg/L, and therefore could be employed for standardization among assays.