Outcomes of percutaneous coronary intervention of chronic total saphenous vein graft occlusions in the contemporary era.

BACKGROUND: Percutaneous coronary intervention of a chronic total occlusion to a saphenous vein graft is currently not recommended because the benefit/risk ratio is considered unfavorable. However, there is a patient subset with clinical ischemia, and PCI of the native chronic total occlusion (CTO) is unfavorable. In this setting, PCI to the saphenous vein graft (SVG) may have utility. We reviewed our experience to determine its value in the modern era. METHODS AND RESULTS: This was a single-center retrospective study of all patients undergoing PCI to SVG CTO. Of 161 patients undergoing SVG PCI during the study period, 27 patients underwent 28 SVG CTO PCI, which was technically successful in 79% (22/28). There were 2 intra-procedural Q wave myocardial infarctions. At 30 days there were no adverse events after hospital discharge. Angina relief was significantly better at 30 days in successful (n = 21) vs. unsuccessful (n = 6) PCI(90% vs. 33% P < 0.01). At the last available follow-up (591 ± 407 days), angina improvement persisted (80.1% vs. 33%, P < 0.01). Long-term adverse events were not significantly different between the two groups. CONCLUSION: PCI to SVG CTO is feasible with a reasonable success rate, safety profile, and improvement in angina in contemporary practice. This approach may be considered in highly selected patients where revascularization to the ischemic territory is appropriate and the native CTO is technically difficult to recanalize.

Effect of Joint National Committee VII report on hospitalizations for hypertensive emergencies in the United States.

Approximately 1% to 2% of patients with hypertension will have a hypertensive emergency at some time in their life. However, no data are available on the frequency of hospitalizations for a hypertensive emergency after the publication of the Seventh Joint National Committee (JNC7) on the prevention, detection, evaluation, and treatment of high blood pressure. We sought to explore the changes in the frequency of hospitalizations and in-hospital mortality for hypertensive emergencies before and after the JNC7 report. Using the Nationwide Inpatient Sample from 2000 to 2007, adult patients (aged ≥18 years) who were hospitalized with a diagnosis of a hypertensive emergency were identified through appropriate "International Classification of Diseases, 9th revision, Clinical Modification" codes. A total of 456,259 hospitalizations with the diagnosis of hypertensive emergency occurred from the start of calendar year 2000 to the end of calendar year 2007. After adjusting for the United States census for 2000 and American Community Survey estimates for 2007 for adults, the frequency of hospitalizations with a hypertensive emergency increased in United States adults from 101/100,000 in 2000 to 111/100,000 in 2007, an average increase of about 1.11%. Despite the increase in hospitalizations, the all-cause in-hospital mortality rate decreased from 2.8% in the pre-JNC7 era to 2.6% in the post-JNC7 era (odds ratio 0.91, 95% confidence interval 0.86 to 0.96). In conclusion, the results of the present study have shown that although the number of patients with hypertensive emergency increased from 2000 to 2007, the mortality rates decreased significantly after the JNC7 guidelines.

Triad of metabolic syndrome, chronic kidney disease, and coronary heart disease with a focus on microalbuminuria death by overeating.

Coronary heart disease remains a major cause of morbidity and mortality in the United States, and its incidence is rising worldwide. Because atherosclerosis is a chronic process, and it is often associated with certain lifestyle and risk factors such as hypertension, dyslipidemia, and insulin resistance, much emphasis is being placed on lifestyle modification and control of risk factors. It is being recognized that some lifestyle patterns such as overeating result in metabolic syndrome, which may play a role in the development of chronic kidney disease and coronary heart disease. Here, we focus on an important relationship between these 3 conditions, and we provide evidence that microalbuminuria develops in many patients with metabolic syndrome, may be an important correlate of chronic kidney disease and coronary heart disease, and may represent an important prognostic marker. Although the pathogenesis of microalbuminuria in metabolic syndrome is not clear, we suggest that microalbuminuria, chronic kidney disease, and coronary heart disease share common pathways involving inflammation and oxidative stress. We also discuss that a healthy lifestyle is essential for preventing and treating chronic kidney disease and coronary heart disease seen in patients with metabolic syndrome.

Management of dyslipidemia in the elderly population.

The elderly population is increasing worldwide. Despite a major decrease in deaths from coronary heart disease (CHD), this malady remains the major cause of death in elderly men and women. In this paper, we review the role of dyslipidemia as a major known risk factor in the pathogenesis of CHD, age-related changes in lipoprotein metabolism, and differences in changes in lipids that occur in men and women during aging. Next we provide an overview of the available studies and recommendations from ATP III. Finally, we comment on the screening and management, cost and side effects of therapy as it applies to an aging population.

Cyclooxygenase inhibition is associated with downregulation of apolipoprotein AI promoter activity in cultured hepatoma cell line HepG2.

Prostanoids have been implicated in the transcriptional control of several genes. Since prostanoid synthesis inhibitors are commonly used in subjects with coronary heart disease we studied the effect of cyclooxygenase (COX) inhibition on apolipoprotein AI (apoAI) expression in a human hepatoma cell line (HepG2) transfected with full-length apoAI promoter attached to the chloramphenicol acetyl transferase (CAT) reporter gene. To control for transfection efficiency, the cells were cotransfected with the plasmid pCMV.SPORT-beta-gal containing the beta-galactosidase gene driven by the cytomegalovirus promoter. Treatment of these cells with varying concentrations of indomethacin (INDO, 0, 50, 100, and 300 micromol/L) resulted in a dose-dependent decrease in apoAI promoter activity (% acetylation corrected for beta-galactosidase activity: were 46.1 +/- 2.6, 29.9 +/- 1.2, 25.2 +/- 2.9, and 17.2 +/- 2.8, respectively, P <.001). INDO treatment did not cause significant changes in beta-galactosidase activity. A similar reduction in apoAI promoter activity was found after treating the cells with 50 micromol/L acetylsalicylic acid (ASA) (31.8 +/- 1.8%, P <.001), suggesting that the effect of INDO is related to COX inhibition rather than a peculiar effect of INDO. Nuclear run-off assays indicated that treatment of cells with 50 micromol/L INDO resulted in 31.4% reduction in apo A1 transcription rate (P <.0002). Northern blot analysis of RNA from HepG2 cells treated with 50 micromol/L of INDO for 72 hours showed that the apoAI mRNA concentration relative to G3PDH mRNA was 4,043.0 +/- 84.6 and 3,064.0 +/- 49.8 in control and INDO-treated cells, respectively (P <.0006). Kinetic studies of apoAI mRNA in HepG2 cells indicated that the half-life of apoAI mRNA was not significantly altered with 50 micromol/L INDO treatment. Apo AI mRNA half-life was 25.3 hours in control cells and 26.9 hours in INDO-treated cells. Western blot analysis of culture media of HepG2 cells treated with 50 micromol/L of INDO for 72 hours showed a significant reduction in apoAI protein (6,760.0 +/- 318.1 v 4,773.0 +/- 112.0 arbitrary units, P <.004). Treatment of cells with either arachidonic acid (COX substrate) or various prostanoids including prostaglandin I(2), thromboxane B(2), (+/-)5-HETE, or (+/-)12-HETE did not significantly alter apoAI promoter activity. However, prostaglandin E(1) and E(2) at the highest concentration tested (50 nmol/L) significantly repressed apoAI promoter activity. COX activity measurements in HepG2 cells verified the efficacy of COX inhibition by INDO. It is concluded that COX inhibition with INDO or ASA downregulates apoAI expression at the transcriptional level. This effect could not be attributed to either arachidonic acid excess or to a deficiency in various prostanoids tested.

Effect of chromium on apolipoprotein A-I expression in HepG2 cells.

OBJECTIVE: Chromium is a key micronutrient required for lipid and carbohydrate metabolism. Some but not all clinical trials have associated use of chromium supplements with improved insulin sensitivity and lipid profile including increased high-density lipoprotein cholesterol levels. METHODS: Because apolipoprotein A-I (apoA-I) is the principal protein of high-density lipoprotein, the molecular pathways underlying chromium-related changes in apoA-I expression were studied in a human hepatoma cell line (HepG2) transfected with full-length apoA-I promoter attached to the reporter chloramphenicol acetyl transferase gene. RESULTS: Exposure of these cells to different concentrations of chromium chloride (0, 0.5, 1.0, and 3.0 mM) resulted in a dose-dependent decrease in apoA-I promoter activity (chloramphenicol acetyl transferase activity expressed as a percentage of an internal control was 99.4 +/- 7.2% in control cells versus 87.6 +/- 5.0%, 73.4 +/- 2.3%, and 36.6 +/- 3.9%, respectively, P < 0.01). Chromium chloride at 10 mM concentration was toxic and caused death in a large number of cells. Treating HepG2 cells with other minerals known to have insulin-sensitizing effects such as magnesium (1 mM), zinc (0.2 mM), and vanadyl sulfate (0.1 mM) significantly reduced apoA-I promoter activity in the presence and absence of 100 microU/mL of insulin. Northern blot analyses showed that the apoA-I mRNA content of cells treated with 0.2 mM of chromium chloride relative to G3PDH mRNA was not significantly increased compared with controls (0.652 +/- 0.122 versus 0.745 +/- 0.143, the ratio of apoA-I to glyceraldehyde 3-phosphate dehydrogenase (G3PDH) mRNA in control and chromium-treated cells, respectively). Western blot analyses of proteins secreted in culture media indicated that neither chromium treatment of the HepG2 cells (858.0 +/- 151.4 arbitrary units) nor treatment with magnesium (1323.3 +/- 175.7) or vanadium (1102 +/- 78.7) significantly altered apoA-I concentrations compared with controls (1061.7 +/- 114.7). However treatment of HepG2 cells with 0.2 mM of zinc significantly reduced apoA-I concentrations (291.0 +/- 29.2 versus 1061.7 +/- 114.7; P < 0.001). CONCLUSIONS: Supraphysiologic concentrations of chromium and other minerals with known insulin-sensitizing activity may reduce apoA-I promoter activity in cultured cells. Whether similar changes may occur in vivo remains to be shown. However, these observations do not support the use of pharmacologic amounts of chromium supplementation to enhance the cardioprotective lipid profile.