Crusan, Daniel J.

Abstract Background: Active cancer without or with chemotherapy is associated with a 4- to 6.5-fold increased risk for VTE 1. However, cancer-associated VTE incidence may be under- or overestimated by reports that linked cancer registry data to an anticoagulation clinic database or to hospital discharge diagnosis codes 2–5. Objective: To estimate the incidence of VTE in active cancer in a well-defined geographic population that includes the full spectrum of VTE events (including rapidly fatal events) occurring in the community. Methods: Using the longitudinal resources of the Rochester Epidemiology Project and Mayo Clinic Tumor Registry, we identified all Olmsted County, MN residents with incident VTE by review of their complete medical records in the community 6, and all residents with active cancer (by cancer site), over the 28-year period, 1973–2000. Using residents with active cancer within the three months prior or subsequent to incident VTE as the numerator, and all residents with active cancer as the denominator, we estimated the incidence of VTE in active cancer, both overall and for the subsets of pancreatic cancer, brain cancer and lymphoma. Results: Over 78,236 active-cancer person-years, 595 Olmsted County residents developed incident VTE. The overall active cancer-associated VTE incidence was 760 per 100,000 person-years (95% CI: 701, 824), about 6.5-fold higher than the general population 7. Over 473, 983 and 4,258 pancreatic cancer, brain cancer and lymphoma person-years, respectively, 51, 18 and 46 residents developed incident VTE. The pancreatic cancer-, brain cancer- and lymphoma-associated VTE incidence rates were 10,784 (95% CI: 8029, 14,179), 1,831 (95% CI: 1085, 2,893) and 1,080 (95% CI: 791, 1,441) per 100,000, respectively. Overall, cancer-associated VTE incidence increased with age, and for all ages, men had a higher VTE rate than women. We observed a much higher pancreatic cancer-associated VTE incidence than previously reported. Conclusions: The incidence of VTE in individuals with active cancer (especially pancreatic cancer) is higher than the general population. The incidence of VTE in patients with pancreatic cancer is higher than previously estimated.

Abstract Abstract 5118 Background: Increased factor VIII:C (FVIII:C) and hypofibrinolysis are VTE risk factors, and beta-blockers and angiotensin converting enzyme (ACE) inhibitors reduce FVIII:C and enhance fibrinolysis, respectively. Objective: To test the hypotheses that beta-blockers and ACE inhibitors reduce VTE risk. Methods: Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988–2000 (n=1306), and one to two Olmsted County residents per case matched on age, event year and duration of prior medical history (n=1500). For cases and controls, we reviewed their complete medical history in the community for previously-identified VTE risk factors (e.g., hospitalization with or without surgery, nursing home confinement, trauma/fracture, leg paresis, active cancer, superficial vein thrombosis and varicose veins), as well as body mass index (BMI), coronary artery disease (CAD), congestive heart failure (CHF), and the use of statins, beta-blockers, ACE inhibitors and angiotensin II receptor antagonist drugs. Using conditional logistic regression, we tested beta-blockers and ACE inhibitors/angiotensin II receptor antagonists for an association with VTE, both individually and after adjusting for age, BMI, previously-identified VTE risk factors, CAD, CHF and the use of statins. Results: Among cases and controls respectively, 191 and 173 received beta-blockers, and 171 and 154 received ACE inhibitors/angiotensin II receptor antagonists. Univariately, both beta-blockers (unadjusted OR=1.31; p=0.02) and ACE inhibitors/angiotensin II receptor antagonists (unadjusted OR=1.32; p=0.02) were modestly associated with increased VTE risk. However, after controlling for age, BMI, previously-identified VTE risk factors, CAD, CHF and the use of statins, beta-blockers (OR=1.06; 95% CI: 0.74, 1.51; p=0.75) and ACE inhibitors/angiotensin II receptor antagonists (OR=0.94; 95% CI: 0.65, 1.37; p=0.75) were no longer associated with VTE. Conclusions: Beta-blockers and ACE inhibitors/angiotensin II receptor antagonists do not appear to be protective against VTE. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2256 Background: The incidence of venous thromboembolism (VTE) may be increasing due to the obesity epidemic. Objective: To estimate the incidence of VTE and describe trends in incidence adjusted for the population's increase in BMI. Methods: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with an incident deep vein thrombosis (DVT) or pulmonary embolism (PE) over the 13-year period, 1988–2000 (n=1,400). Age and BMI at VTE diagnosis and gender were collected for all cases. Age was categorized into 10 year intervals. Using a model for the population distribution of BMI derived from several (n=6) non-VTE Olmsted County cohorts (n=8,011 individuals), we calculated the probability of falling into each of five BMI categories (<18.5, 18.5–24, 25–29, 30–34, 35+) for each age, gender and calendar year. In Olmsted County in the median age group, the prevalence of BMI >30 kg/m2increased from approximately 15% in 1980 to 36% in 2000. We applied these probabilities to the decennial census data for 1980, 1990, 2000 using linearly interpolated census values for intra-census years to obtain Olmsted County age/sex/calendar year/BMI category denominators. Generalized linear modeling assuming a Poisson error structure, and using a log link function, and a log (population) offset was used to assess the relationship of crude incidence rates to gender, year of diagnosis, age and BMI. Results: The overall average age- and sex-adjusted annual VTE incidence was 120 per 100,000 person-years (DVT: 66 per 100,000; PE: 54 per 100,000), with higher age-adjusted rates among men than women (129 versus 113 per 100,000, respectively). VTE incidence rates increased exponentially with age for both genders, ranging from 3 to 1,079 per 100,000 for age groups 0–19 to 90–110 years. Age and sex-adjusted VTE incidence increased by increasing BMI category (88, 112, 106, 150, and 195 per 100,000 person-years, respectively, by increasing BMI category). Unadjusted for BMI, VTE incidence was unchanged from 1988 through 2000 (p=0.70). After adjusting for age, gender and calendar year, VTE incidence increased with increasing BMI (p<0.0001). The calendar year incidence slope estimate decreased numerically from 3% per decade to minus 4% per decade after adjusting for increasing BMI, remaining nonsignificant (p=0.57). Conclusions: VTE remains a major national health problem, especially among the obese. Despite the dramatically increasing population BMI, and the significant association of BMI category with VTE incidence, the overall incidence of VTE remained unchanged over the timeframe, 1988–2000. Disclosures: No relevant conflicts of interest to declare.

Background: We aim to study the incidence of major complications related to procedure defined as in-hospital death, myocardial infarction, stroke, pericardial effusion or tamponade, percutaneous coronary intervention due to iatrogenic coronary dissection, or unplanned bypass surgery within 72 hours after diagnostic left heart catheterization (LHC; primary end point). Furthermore, all causes of in-hospital death after LHC were adjudicated and reported (secondary end point). Methods and Results: Diagnostic LHC procedures (aortic angiography; coronary, including graft, angiography; and left ventricular angiography) from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system at Mayo Clinic, Rochester, and complications were identified through electronic records. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All events were reviewed and adjudicated. There were 43 786 diagnostic LHC procedures; 97.3% were coronary angiograms. The mean age of patients was 64.5 years (13.6), and the majority were male (61.5%). Primary end point was seen in 36 (0.082%) procedures or 8.2 of 10 000 LHCs. Combined right sided procedures with LHC did not increase the risk of major complications. Cardiogenic and septic shock, cardiac arrhythmia, and postsurgical complication were the most common causes of in-hospital death after LHC. Conclusions: The overall rates of major complications related to diagnostic cardiac catheterization procedures are extremely rare. The majority of the deaths occurring post-diagnostic LHC procedures were secondary to acute illness rather than directly related to diagnostic procedure.

Background— Women have higher rates of all-cause mortality after percutaneous coronary intervention. Whether this is because of greater age and comorbidity burden or a sex-specific factor remains unclear. Methods and Results— We retrospectively assessed cause-specific long-term mortality after index percutaneous coronary intervention over 3 time periods (1991–1997, 1998–2005, and 2006–2012). Cause of death was determined using telephone interviews, medical records, and death certificates. We performed competing risks analyses of cause-specific mortality. A total of 6847 women and 16 280 men survived index percutaneous coronary intervention hospitalization 1991 to 2012. Women were older (mean±SD: 69.4±12 versus 64.8±11.7 years; P <0.001) with more comorbidities (mean±SD: Charlson index 2.1±2.1 versus 1.9±2.1; P <0.001). Across the 3 time periods, both sexes exhibited a decline in cardiac deaths at 5 years (26% relative decrease in women, 17% in men, trend P <0.001 for each). Although women had higher all-cause mortality compared with men in all eras, the excess mortality was because of noncardiac deaths. In the contemporary era, only a minority of deaths were cardiac (33.8% in women, 38.0% in men). After adjustment, there was no evidence for a sex-specific excess of risk for cardiac or noncardiac mortality. The commonest causes of death were chronic diseases and heart failure in women (5-year cumulative mortality, 5.4% and 3.9%) but cancer and myocardial infarction/sudden death in men (5.4% and 4.3%). Conclusions— The higher mortality after percutaneous coronary intervention in women is because of death from noncardiac causes. This is accounted for by baseline age and comorbidities rather than an additional sex-specific factor. These findings have implications for sex-specific clinical care and trial design.

Background Participation in cardiac rehabilitation ( CR ) is an essential component of care for patients with coronary artery disease. However, little is known about its benefit on cardiovascular outcomes in patients with diabetes mellitus ( DM ) who have undergone percutaneous coronary intervention. The aim of our study was to evaluate the impact of CR in this high‐risk group of patients. Methods and Results We performed a retrospective analysis of all patients with DM who underwent percutaneous coronary intervention in Olmsted County (Minnesota) between 1994 and 2010, assessing the impact of CR participation on clinical outcomes. CR participation was significantly lower in patients with DM (38%, 263/700) compared with those who did not have DM (45%, 1071/2379; P =0.004). Using propensity score adjustment, we found that in patients with DM , CR participation was associated with significantly reduced all‐cause mortality (hazard ratio, 0.56; 95% confidence interval, 0.39–0.80; P =0.002) and composite end point of mortality, myocardial infarction, or revascularization (hazard ratio, 0.77; 95% confidence interval, 0.60–0.98; P =0.037), during a median follow‐up of 8.1 years. In patients without DM , CR participation was associated with a significant reduction in all‐cause mortality (hazard ratio, 0.67; 95% confidence interval, 0.55–0.82; P <0.001) and cardiac mortality (hazard ratio, 0.67; 95% confidence interval, 0.47–0.95; P =0.024). Conclusions CR participation after percutaneous coronary intervention is associated with lower all‐cause mortality rates in patients with DM , to a similar degree as for those without DM . However, CR participation was lower in patients with DM , suggesting the need to identify and correct the barriers to CR participation for this higher‐risk group of patients.

Background— There has been a gradual decline in the prevalence of abnormal stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging studies among patients without history of coronary artery disease (CAD). The trends of SPECT studies among patients with known CAD have not been evaluated previously. Methods and Results— We assessed the Mayo Clinic nuclear cardiology database for all stress SPECT tests performed between January 1991 and December 2012 in patients with history of CAD defined as having previous myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. The study cohort was divided into 5 time periods: 1991 to 1995, 1996 to 2000, 2001 to 2005, 2006 to 2010, and 2011 to 2012. There were 19 373 patients with a history of CAD who underwent SPECT between 1991 and 2012 (mean age, 66.2±10.9 years; 75.4% men). Annual utilization of SPECT in these patients increased from an average of 495 tests per year in 1991 to 1995 to 1425 in 2003 and then decreased to 552 tests in 2012 without evidence for substitution with other stress modalities. Asymptomatic patients initially increased until 2006 and then decreased. Patients with typical angina decreased, whereas patients with dyspnea and atypical angina increased. High-risk SPECT tests significantly decreased, and the percentage of low-risk SPECT tests increased despite decreased SPECT utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had a low-risk summed stress score compared with 29% in 1991 ( P <0.001). Conclusions— In Mayo Clinic, Rochester, annual SPECT utilization in patients with previous CAD increased between 1992 and 2003, but then decreased after 2003. High-risk SPECT tests declined, whereas low-risk tests increased markedly. Our results suggest that among patients with a history of CAD, SPECT was being increasingly utilized in patients with milder CAD. This trend parallels reduced utilization of other stress modalities, coronary angiography, reduced smoking, and greater utilization of optimal medical therapy for prevention and treatment of CAD.

Key PointsApproximately 500 000 US VTE events occur annually; approximately one-half are related to current or recent hospitalization. VTE attack rates (2005-2010) did not change despite near-universal in-hospital VTE prophylaxis, possibly due to short prophylaxis duration.