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1. Cardiovascular pharmacogenomics: current status, future prospects

Author

Anderson, Jeffrey L., Carlquist, John F., Home, Benjamin D., and Muhlestein, Joseph B.

Subjects
Pharmacogenetics -- Research, Cardiovascular agents -- Physiological aspects, Pharmaceutical research -- Methods, Cardiovascular diseases -- Drug therapy, Health
Published
2003

2. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies

Author

Thompson, Alexander, Gao, Pei, Orfei, Lia, Watson, Sarah, Di Angelantonio, Emanuele, Kaptoge, Stephen, Ballantyne, Christie, Cannon, Christopher P., Criqui, Michael, Cushman, Mary, Hofman, Albert, Packard, Chris, Thompson, Simon G., Collins, Rory, Danesh, John, Willeit, Johann, Kiechl, Stefan, Wiedemann, Christian, Psaty, Bruce, Furberg, Curt, Khaw, Kay-Tee, Sandhu, Manjinder, Benjamin, Emelia J., Vasan, Ramachandran S., Schnabel, Renate B., Oldgren, Jonas, Rossi, Gian Paolo, Cesari, Maurizio, Lenzini, Livia, Zanchetta, Mario, James, Stefan K., Rimm, Eric, Hatoum, Ida, Anderson, Jeffrey L., May, Heidi T., Home, Benjamin D., Carlquist, John F., Muhlestein, Joseph B., Koenig, Wolfgang, Hermann Brenner, Rothenbacher, Dietrich, Maerz, Winfried, Boehm, Bernhard, Winkelmann, Bernhard R., Winkler, Karl, Berglund, Goran, Persson, Margaretha, Roger, Veronique, Gerber, Yariv, Berger, Peter B., Brilakis, Emmanouil S., Mcconnell, Joseph P., Meisinger, Christa, Sacco, Ralph, Elkind, Mitchell, Talmud, Philippa J., O Donoghue, Michelle, Sabatine, Marc S., Morrow, David A., Caslake, Muriel, Braunwald, Eugene, Barrett-Connor, Elizabeth, Daniels, Lori B., Laughlin, Gail A., Kardys, Isabella, Witteman, Jacqueline C. M., Corsetti, James P., Rainwater, David L., Moss, Arthur J., Wassertheil-Smoller, Sylvia, Ridker, Paul, Nelson, Jeanenne J., Zariffa, Nevine, Zalewski, Andrew, and Walker, Mat

Subjects
Male, medicine.medical_specialty, Heart disease, Systole, Blood Pressure, Coronary Disease, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Darapladib, Internal medicine, medicine, Fast track — Articles, Humans, Myocardial infarction, Prospective Studies, Risk factor, Particle Size, 030304 developmental biology, Apolipoproteins B, 0303 health sciences, Framingham Risk Score, business.industry, Vascular disease, Lipoprotein-associated phospholipase A2, General Medicine, Middle Aged, medicine.disease, Lipids, 3. Good health, Lipoproteins, LDL, Stroke, Blood pressure, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Cardiology, Linear Models, lipids (amino acids, peptides, and proteins), Female, business, Biomarkers
Abstract

Background Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an inflammatory enzyme expressed in atherosclerotic plaques, is a therapeutic target being assessed in trials of vascular disease prevention. We investigated associations of circulating Lp-PLA(2) mass and activity with risk of coronary heart disease, stroke, and mortality under different circumstances. Methods With use of individual records from 79 036 participants in 32 prospective studies (yielding 17 722 incident fatal or non-fatal outcomes during 474 976 person-years at risk), we did a meta-analysis of within-study regressions to calculate risk ratios (RRs) per 1 SD higher value of Lp-PLA(2) or other risk factor. The primary outcome was coronary heart disease. Findings Lp-PLA(2) activity and mass were associated with each other (r=0.51, 95% CI 0.47-0.56) and proatherogenic lipids. We noted roughly log-linear associations of Lp-PLA(2) activity and mass with risk of coronary heart disease and vascular death. RRs, adjusted for conventional risk factors, were: 1.10 (95% CI 1.05-1.16) with Lp-PLA(2) activity and 1.11 (1.07-1.16) with Lp-PLA(2) mass for coronary heart disease; 1.08 (0.97-1.20) and 1.14 (1.02-1.27) for ischaemic stroke; 1.16 (1.09-1.24) and 1.13 (1.05-1.22) for vascular mortality; and 1.10 (1.04-1.17) and 1.10 (1.03-1.18) for non-vascular mortality, respectively. RRs with Lp-PLA(2) did not differ significantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA(2) mass. Adjusted RRs for coronary heart disease were 1.10 (1.02-1.18) with non-HDL cholesterol and 1.10 (1.00-1.21) with systolic blood pressure. Interpretation Lp-PLA(2) activity and mass each show continuous associations with risk of coronary heart disease, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population. Associations of Lp-PLA(2) mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids. Funding UK Medical Research Council, GlaxoSmithKline, and British Heart Foundation.

Published
2010

4. Specific polymorphism groups within a PPARg-ABCA1 pathway are associated with future death or myocardial infarction in patients with angiographically documented coronary artery disease

Author

King, Cory A., primary, Muhlestein, Joseph B., additional, Hart, Noal I., additional, Faatz, Jill B., additional, Mulhuizen, Henri O.F., additional, Anderson, Jeffrey L., additional, Whiting, Bryant M., additional, Home, Benjamin D., additional, and Carquist, John F., additional

Published
2002
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10. Improvements in 1-Year Cardiovascular Clinical Outcomes Associated with a Hospital-Based Discharge Medication Program.

Author

Lapp&eacute, Jason M., Muhlestein, Joseph B., Lappé, Donald L., Badger, Rodney S., Bair, Tami L., Brockman, Ruth, French, Thomas K., Hofmann, Linda C., Home, Benjamin D., Kralick-goldberg, Susan, Nicponski, Nan, Orton, Janette A., Pearson, Robert R., Renlund, Dale G., Rimmasch, Holly, Roberts, Colleen, and Anderson, Jeffrey L.

Subjects
CARDIOVASCULAR diseases, DRUG utilization, PREVENTIVE medicine, HOSPITAL admission & discharge, HOSPITAL care, MULTIHOSPITAL systems
Abstract

Background: Despite recent advances in the treatment and prevention of cardiovascular disease, a treatment gap for secondary prevention medications still exists. Objective: To develop and implement a program ensuring appropriate prescription of aspirin, statins, β-blockers, angiotensin-converting enzyme inhibitors, and warlarin at hospital discharge. Design: A nonrandomized before-after study comparing patients hospitalized before (1996-1998) and after (1999-2002) implementation of a discharge medication program (DMP). Patients were followed for up to 1 year. Setting: The 10 largest hospitals in the Utah-based Intermountam Health Care system. Patients: In the pre-DMP and DMP time periods, 26 000 and 31 465 patients, respectively, were admitted to cardiovascular services (n = 57465). Measurements: Prescription of indicated medications at hospital discharge; post discharge death or readmission. Results: By 1 year, the rate of prescription of each medication increased significantly to more than 90% (P< 0.001); this rate was sustained. At 1 year, unadjusted absolute event rates for readmission and death, respectively, were 210 per 1000 person-years and 96 per 1000 person-years before OMP implementation and 191 per 1000 person-years and 70 per 1000 person-years afterward. Relative risk for death and readmission at 30 days decreased after OMP implementation; hazard ratios (HRs) for death and readmission were 0.81 (95% CI, 0.73 to 0.89) and 0.92 (CI, 0.87 to 0.99) (P < 0.001 and P = 0.017, respectively). At I year, risk for death continued to decrease (hazard ratio, 0.79 [CI, 0.75 to 0.84]; P < 0.001) while risk for readmission stabilized (hazard ratio, 0.94 [CI, 0.90 to 0.98]; P= 0.002), probably because survivors had more opportunities to be readmitted. Limitations: The study design was observational and nonrandomized, and the authors could not control for potential confounders or determine the extent to which secular trends accounted for the observed improvements. Conclusions: A relatively simple quality improvement program aimed at enhancing the prescription of appropriate discharge medications among cardiovascular patients is feasible and can be sustained within an integrated multihospital system. Such a program may be associated with improvements in cardiovascular readmission rates and mortality. [ABSTRACT FROM AUTHOR]

Published
2004
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11. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies

Author

Thompson, Alexander, Pei Gao, Orfei, Lia, Watson, Sarah, Di Angelantonio, Emanuele, Kaptoge, Stephen, Ballantyne, Christie, Cannon, Christopher P., Criqui, Michael, Cushman, Mary, Hofman, Albert, Packard, Chris, Thompson, Simon G., Collins, Rory, Danesh, John, Willeit, Johann, Kiechl, Stefan, Wiedemann, Christian, Psaty, Bruce, Furberg, Curt, Khaw, Kay-Tee, Sandhu, Manjinder, Benjamin, Emelia J., Vasan, Ramachandran S., Schnabel, Renate B., Oldgren, Jonas, Rossi, Gian Paolo, Cesari, Maurizio, Lenzini, Livia, Zanchetta, Mario, James, Stefan K., Rimm, Eric, Hatoum, Ida, Anderson, Jeffrey L., May, Heidi T., Home, Benjamin D., Carlquist, John F., Muhlestein, Joseph B., Koenig, Wolfgang, Brenner, Herrnann, Rothenbacher, Dietrich, Maerz, Winfried, Boehm, Bernhard, Winkelmann, Bernhard R., Winkler, Karl, Berglund, Goran, Persson, Margaretha, Roger, Veronique, Gerber, Yariv, Berger, Peter B., Brilakis, Emmanouil S., Mcconnell, Joseph P., Meisinger, Christa, Sacco, Ralph, Elkind, Mitchell, Talmud, Philippa J., O Donoghue, Michelle, Sabatine, Marc S., Morrow, David A., Caslake, Muriel, Braunwald, Eugene, Barrett-Connor, Elizabeth, Daniels, Lori B., Laughlin, Gail A., Kardys, Isabella, Witteman, Jacqueline C. M., Corsetti, James P., Rainwater, David L., Moss, Arthur J., Wassertheil-Smoller, Sylvia, Ridker, Paul, Nelson, Jeanenne J., Zariffa, Nevine, Zalewski, Andrew, Walker, Mat, and Lp-PLA2 Studies Collaboration

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