Comorbidities and Concomitant Medication Use in Men with Prostate Cancer or High Levels of PSA Compared to Matched Controls: A GPRD Analysis

Comorbidity influences screening practice, treatment choice, quality of life, and survival. The presence of comorbidities and medication use could place patients at greater risks of adverse effects from certain interventions. We conducted a longitudinal cohort study in the General Practice Research Database to better understand comorbidities and medication use in men with or at risk of prostate cancer (CaP). Compared with men with similar age but no CaP, CaP patients had higher incidence of urinary tract infection, impotence and breast disorder, and 2.6-fold higher all-cause mortality. Among men with elevated prostate-specific antigen (PSA) but no CaP, the mortality rates were slightly lower, and fewer differences in comorbidities and medication use were noted compared to men without elevated PSA. Many prevalent comorbidities and medications were consistent across groups and are typical of an older male population. These real-world data are broadly applicable throughout the drug development cycle and subsequent patient management

The association between lipoprotein-associated phospholipase A2 and cardiovascular disease and total mortality in vascular medicine patients

IntroductionIn some community-based studies, lipoprotein-associated phospholipase A2 (Lp-PLA2) has been shown to be independently predictive of future fatal and nonfatal cardiovascular disease (CVD) events. We tested the hypothesis that Lp-PLA2 is independently predictive of mortality in high-risk patients from a vascular laboratory.MethodsBetween 1990 and 1994, patients seen in the previous 10 years for noninvasive lower extremity arterial testing were invited to return for a vascular examination of the lower extremities. By medical record review, we identified 2265 eligible patients; of these, 508 returned for interviews, blood collection, and arterial examination and represent those who had survived, could be located, and were willing to participate. The 508 subjects were followed up for an average of 6.7 years until the end of the study period on December 31, 2001. Vital status was ascertained by multiple searches of the Social Security Death Index. The primary outcomes for this study were time to any, CVD, and coronary heart disease (CHD) mortality.ResultsThe mean age was 68.2 years, 88% were men, 87% were non-Hispanic white, 39.1% were diagnosed with peripheral arterial disease only, 9.2% with other CVD only, and 28.5% with both peripheral arterial disease and other CVD. During the entire follow-up period, 299 (59.7%) patients died, 167 from CVD, of which 88 deaths were due to coronary heart disease. With adjustment for CVD risk factors and baseline peripheral arterial disease and other CVD, an increment of one standard deviation in Lp-PLA2 activity was associated with a 40% higher risk for CHD mortality at 5 years of follow-up (P = .04). Additional adjustment for triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol reduced this association to nonsignificance (hazard risk, 1.12).ConclusionIn a vascular laboratory patient population, higher levels of LpPLA2 mass and activity were not significantly associated with total, CVD, or CHD mortality at 5 years of follow-up and after adjustment for traditional CVD risk factors and the presence of PAD and other CVD at baseline. An apparent elevated risk of CHD death associated with elevated Lp-PLA2 was largely explained by associated elevations in lipids and lipoproteins

Disruptions in Liver Function among Cancer Patients and Patients Treated with Tyrosine Kinase Inhibiting Drugs: Comparisons of Two Population-Based Databases

Liver toxicity is a recognized adverse event associated with small molecule tyrosine kinase inhibitors (TKIs). Electronic Medical Record (EMR) databases offer the most precise data to investigate the rate of liver function test (LFT) elevations; however, they can be limited in sample size and costly to access and analyze. Health insurance claims databases often contain larger samples sizes but may lack key health information. We evaluated the feasibility of utilizing a large claims database to calculate incidence rates (IRs) of LFT elevations among a general cohort of cancer patients and a cohort of patients treated with TKIs by comparing the results to a “gold standard” oncology-specific EMR database. IRs for the TKI cohorts were very similar between the two databases; however, IRs were higher in the EMR database for the cancer cohorts. Possible explanations for these differences include lack of specificity when defining a cancer case, poor capture of laboratory data, or inaccurate assessment of person-time in the insurance claims database. This study suggests that insurance claims data may provide reliable results when investigating liver toxicities associated with oncology drug exposure; however, there are limitations when assessing laboratory outcomes for cohorts defined solely by disease status

The association of the ankle-brachial index with incident coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study, 1987-2001

Abstract Background Peripheral arterial disease (PAD), defined by a low ankle-brachial index (ABI), is associated with an increased risk of cardiovascular events, but the risk of coronary heart disease (CHD) over the range of the ABI is not well characterized, nor described for African Americans. Methods The ABI was measured in 12186 white and African American men and women in the Atherosclerosis Risk in Communities Study in 1987–89. Fatal and non-fatal CHD events were ascertained through annual telephone contacts, surveys of hospital discharge lists and death certificate data, and clinical examinations, including electrocardiograms, every 3 years. Participants were followed for a median of 13.1 years. Age- and field-center-adjusted hazard ratios (HRs) were estimated using Cox regression models. Results Over a median 13.1 years follow-up, 964 fatal or non-fatal CHD events accrued. In whites, the age- and field-center-adjusted CHD hazard ratio (HR, 95% CI) for PAD (ABI 1.0, in all race-gender subgroups. The association between the ABI and CHD relative risk was similar for men and women in both race groups. A 0.10 lower ABI increased the CHD hazard by 25% (95% CI 17–34%) in white men, by 20% (8–33%) in white women, by 34% (19–50%) in African American men, and by 32% (17–50%) in African American women. Conclusion African American members of the ARIC cohort had higher prevalences of PAD and greater risk of CHD associated with ABI-defined PAD than did white participants. Unlike in other cohorts, in ARIC the CHD risk failed to increase at high (>1.3) ABI values. We conclude that at this time high ABI values should not be routinely considered a marker for increased CVD risk in the general population. Further research is needed on the value of the ABI at specific cutpoints for risk stratification in the context of traditional risk factors

The epidemiology of Lp-PLA(2): Distribution and correlation with cardiovascular risk factors in a population-based cohort.

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an enzyme that is produced by inflammatory cells (macrophages, T-lymphocytes and mast cells) and hydrolyzes oxidized phospholipids in LDL. Several epidemiology studies indicate that Lp-PLA(2) appears to be an independent marker of cardiovascular risk. This study was conducted to define the distribution of Lp-PLA(2) in a large population-based cohort and to determine associations between Lp-PLA(2) and other risk factors for CVD. The study group consisted of participants from the Malmo Diet and Cancer study (1992-1994). Lp-PLA(2) (activity and mass) was measured from samples obtained at baseline for 5402 participants (3167 women). A strong correlation was observed between Lp-PLA(2) activity and mass in this study (r = 0.57). Highest correlations were observed between Lp-PLA(2) activity and LDL (r=0.45) and LDL/HDL ratio (r=0.54) and a strong inverse correlation to HDL (r=-0.31). The correlations between Lp-PLA(2) mass and lipids were not as strong as the correlation between activity and lipids. Lp-PLA(2) activity and mass were correlated with increased ultrasound determined carotid intima-media thickness. We conclude that Lp-PLA(2) is strongly correlated with several cardiovascular risk factors, especially lipid fractions, and with the degree of carotid artery atherosclerosis. However, the measured variables accounted for only 19% and 35% of the variation in Lp-PLA(2) mass and activity respectively. (c) 2006 Elsevier Ireland Ltd. All rights reserved