Jacobsen, Steven J.

0024 Background: There is evidence for the role of inflammation in the pathogenesis of coronary disease. Relative lymphocytopenia was reported for the diagnosis of myocardial infarction (MI), but little is known about its prognostic value. This study was undertaken to test the hypothesis that relative lymphocytopenia was associated with cardiac events (defined as recurrent MI, congestive heart failure or cardiac death) after MI among Olmsted County residents. Methods: MIs were validated using standard epidemiological criteria using enzymes, chest pain and Minnesota coding of the ECG. The entire community medical record, available via the Rochester Epidemiology Project, was reviewed to determine incident status and ascertain outcomes. Relative lymphocytopenia was defined as percent lymphocytes<20, 3%. Results: Between 1979 and 1994, an incidence cohort of 1653 validated MIs (mean age 67 ± 14, 43% women) was assembled. At the time of index MI, relative lymphocytopenia was present in 51% of the cases. After a mean follow-up of 6.9 ± 5.4 years, 471 pts had experienced recurrent MIs, 849 pts CHF and 602 cardiac deaths occurred. The 5-year event-free survival was 35% for cases with relative lymphocytopenia vs 52% for those without(p<0.001). After adjustment for age and current smoking, relative lymphocytopenia was associated with a 21% increase in the risk of cardiac event (RR 1.21, 95% CI 1.1-1.4; p=0.003). Conclusion: Relative lymphocytopenia is associated with cardiac events after incident MI. These data support the role of inflammation in the outcome of coronary disease.

P46 While heart failure (HF), an emerging epidemic, complicates myocardial infarction (MI), little is known on the predictors of HF post-MI, in particular the impact of reperfusion therapy. This population-based study was undertaken to examine the association between clinical characteristics and post-MI HF between 1979 and 1994. Hospitalized incident MIs were validated using enzymes, chest pain, and Minnesota coding of the ECG. Framingham criteria were used to ascertain both in- and outpatient HF. Proportional hazard regression was used to identify predictors of CHF. In the study period, 1657 patients (pts.) (mean age 67.2 ± 13.9 years, 43% women) had an incident MI. History of diabetes, hypertension and prior HF was found in 19%, 54% and 11% of pts respectively. After 5 years, 43% of pts had experienced HF. Factors independently associated with HF were (see table). There was a 2% decline per year in occurrence of HF. Adding reperfusion therapy in the model attenuated the association between year and HF (adjusted RR for reperfusion 0.67, 95% CI 0.53, 0.84, p=0.006; adjusted for year 0.99; 95% CI 0.97, 1.01, p=0.37). Thus, while remaining frequent post-MI CHF has declined over time. Reperfusion therapy accounted for most of the effect of year. Table 1.

AbstractBackground: Human glandular kallikrein (hK2) is a serine protease that has 79% amino acid identity with prostate-specific antigen (PSA). Both free hK2 and hK2 complexed to α1-antichymotrypsin (ACT) are present in the blood in low concentrations. We wished to measure hK2 in serum with limited contribution from hK2-ACT for the results.Methods: We developed an automated assay for hK2 with use of a select pair of monoclonal antibodies. The prototype assay was implemented on a Beckman Coulter ACCESS® analyzer.Results: The detection limit of the assay was 1.5 ng/L, the “functional sensitivity” (day-to-day CV &lt;15%) was &lt;4 ng/L, cross-reactivity with PSA and PSA-ACT was negligible, and cross-reactivity with hK2-ACT was 2%. After surgical removal of prostate glands, serum hK2 was &lt;7 ng/L and was &lt;15 ng/L in most healthy women. The median serum concentration of hK2 in healthy men without prostate cancer was 26 ng/L. The median concentration of hK2 was 72 ng/L for men having prostate cancer with lower Gleason scores compared with 116 ng/L for men with more advanced cancer. The concentration of hK2 correlated weakly with PSA, with the mean hK2 concentrations generally 30- to 80-fold lower than PSA concentrations.Conclusion: The availability of a robust, high sensitivity automated assay for hK2 should facilitate further investigations of the role of hK2 measurements in the management of patients with prostate disease.

Significance Statement Kidney stone recurrence can manifest with symptoms from stone passage or with asymptomatic changes in kidney stone burden revealed by radiography. In a multicenter, prospective cohort study, the authors demonstrate that substantially more asymptomatic and self-managed symptomatic kidney stone recurrence occur in stone formers than has been appreciated, as many studies consider only symptomatic recurrence that results in clinical care. Among first-time symptomatic stone formers, 54% had an asymptomatic kidney stone; half of those with such a stone passed it within 5 years (but only half who did so experienced symptoms). The findings also show that when a more comprehensive definition of recurrence that includes all symptomatic and radiological manifestations is used, risk factors better predict kidney stone recurrence, thus supporting a comprehensive assessment of recurrence in clinical trials. Background Meaningful interpretation of changes in radiographic kidney stone burden requires understanding how radiographic recurrence relates to symptomatic recurrence and how established risk factors predict these different manifestations of recurrence. Methods We recruited first-time symptomatic stone formers from the general community in Minnesota and Florida. Baseline and 5-year follow-up study visits included computed tomography scans, surveys, and medical record review. We noted symptomatic recurrence detected by clinical care (through chart review) or self-report, and radiographic recurrence of any new stone, stone growth, or stone passage (comparing baseline and follow-up scans). To assess the prediction of different manifestations of recurrence, we used the Recurrence of Kidney Stone (ROKS) score, which sums multiple baseline risk factors. Results Among 175 stone formers, 19% had symptomatic recurrence detected by clinical care and 25% detected by self-report; radiographic recurrence manifested as a new stone in 35%, stone growth in 24%, and stone passage in 27%. Among those with a baseline asymptomatic stone (54%), at 5 years, 51% had radiographic evidence of stone passage (accompanied by symptoms in only 52%). Imaging evidence of a new stone or stone passage more strongly associated with symptomatic recurrence detected by clinical care than by self-report. The ROKS score weakly predicted one manifestation—symptomatic recurrence resulting in clinical care ( c -statistic, 0.63; 95% confidence interval, 0.52 to 0.73)—but strongly predicted any manifestation of symptomatic or radiographic recurrence (5-year rate, 67%; c -statistic, 0.79; 95% confidence interval, 0.72 to 0.86). Conclusions Recurrence after the first stone episode is both more common and more predictable when all manifestations of recurrence (symptomatic and radiographic) are considered.

Background— Cross-sectional studies suggest that left ventricular (LV) and arterial elastance (stiffness) increase with age, but data examining longitudinal changes within human subjects are lacking. In addition, it remains unknown whether age-related LV stiffening is merely a reaction to arterial stiffening or caused by other processes. Methods and Results— Comprehensive echo-Doppler cardiography was performed in 1402 subjects participating in a randomly selected community-based study at 2 examinations separated by 4 years. From this population, 788 subjects had adequate paired data to determine LV end-systolic elastance (Ees), end-diastolic elastance (Eed), and effective arterial elastance. Throughout 4 years, blood pressure, arterial elastance, and LV mass decreased, coupled with significantly greater use of antihypertensive medications. However, despite reductions in arterial load, Ees increased by 14% (2.10±0.67–2.26±0.70 mm Hg/mL; P <0.0001) and Eed increased by 8% (0.13±0.03–0.14±0.04 mm Hg/mL; P <0.0001). Increases in Eed were greater in women than men, whereas Ees changes were similar. Age-related increases in Ees and Eed were correlated with changes in body weight, but were similar in subjects with or without cardiovascular disease. Changes in Ees were correlated with Eed ( r =0.5; P <0.0001), but not with other measures of contractility, indicating that the increase in Ees was reflective of passive stiffening rather than enhanced systolic function. Conclusions— Despite reductions in arterial load with medical therapy, LV systolic and diastolic stiffness increase over time in humans, particularly in women. In addition to blood pressure control, therapies targeting load-independent ventricular stiffening may be effective to treat and prevent age-associated cardiovascular diseases, such as heart failure.