Lanfang Xu

PURPOSE: Cardiovascular diseases (CVDs), including ischemic heart disease, stroke, and heart failure, are well-established late effects of therapy in survivors of childhood and young adult (< 40 years at diagnosis) cancers; less is known regarding CVD in long-term survivors of adult-onset (≥ 40 years) cancer. METHODS: A retrospective cohort study design was used to describe the magnitude of CVD risk in 36,232 ≥ 2-year survivors of adult-onset cancer compared with matched (age, sex, and residential ZIP code) noncancer controls (n = 73,545) within a large integrated managed care organization. Multivariable regression was used to examine the impact of cardiovascular risk factors (CVRFs; hypertension, diabetes, dyslipidemia) on long-term CVD risk in cancer survivors. RESULTS: Survivors of multiple myeloma (incidence rate ratio [IRR], 1.70; P < .01), carcinoma of the lung/bronchus (IRR, 1.58; P < .01), non-Hodgkin lymphoma (IRR, 1.41; P < .01), and breast cancer (IRR, 1.13; P < .01) had significantly higher CVD risk when compared with noncancer controls. Conversely, prostate cancer survivors had a lower CVD risk (IRR, 0.89; P < .01) compared with controls. Cancer survivors with two or more CVRFs had the highest risk of CVD when compared with noncancer controls with less than two CVRFs (IRR, 1.83 to 2.59; P < .01). Eight-year overall survival was significantly worse among cancer survivors who developed CVD (60%) when compared with cancer survivors without CVD (81%; P < .01). CONCLUSION: The magnitude of subsequent CVD risk varies according to cancer subtype and by the presence of CVRFs. Overall survival in survivors who develop CVD is poor, emphasizing the need for targeted prevention strategies for individuals at highest risk of developing CVD.

BACKGROUND: It is unknown if a survival gap remains between HIV-infected and HIV-uninfected individuals with access to care. METHODS: We conducted a cohort study within Kaiser Permanente California during 1996-2011, using abridged life tables to estimate the expected years of life remaining ("life expectancy") at age 20. RESULTS: Among 24,768 HIV-infected and 257,600 HIV-uninfected individuals, there were 2229 and 4970 deaths, with mortality rates of 1827 and 326 per 100,000 person-years, respectively. In 1996-1997, life expectancies at age 20 for HIV-infected and HIV-uninfected individuals were 19.1 and 63.4 years, respectively, corresponding with a gap of 44.3 years (95% confidence interval: 38.4 to 50.2). Life expectancy at age 20 for HIV-infected individuals increased to 47.1 years in 2008 and 53.1 years by 2011, narrowing the gap to 11.8 years (8.9-14.8 years) in 2011. In 2008-2011, life expectancies at age 20 for HIV-infected individuals ranged from a low of 45.8 years for blacks and 46.0 years for those with a history of injection drug use to a high of 52.2 years for Hispanics. HIV-infected individuals who initiated antiretroviral therapy with CD4 ≥500 cells per microliter had a life expectancy at age 20 of 54.5 years in 2008-2011, narrowing the gap relative to HIV-uninfected individuals to 7.9 years (5.1-10.6 years). For these HIV-infected individuals, the gap narrowed further in subgroups with no history of hepatitis B or C infection, smoking, drug/alcohol abuse, or any of these risk factors. CONCLUSIONS: Even with early treatment and access to care, an 8-year gap in life expectancy remains for HIV-infected compared with HIV-uninfected individuals.

OBJECTIVE: To evaluate the risk of cancers with and without a known infectious cause in HIV-infected persons. DESIGN: Retrospective cohort study. METHODS: Adult HIV-infected and matched HIV-uninfected members of Kaiser Permanente followed between 1996 and 2007 for incident AIDS-defining cancers (ADCs), infection-related non-AIDS-defining cancers (NADCs; anal squamous cell, vagina/vulva, Hodgkin's lymphoma, penis, liver, human papillomavirus-related oral cavity/pharynx, stomach) and infection-unrelated NADC (all other NADCs). RESULTS: We identified 20 277 HIV-infected and 202 313 HIV-uninfected persons. HIV-infected persons experienced 552 ADC, 221 infection-related NADC, and 388 infection-unrelated NADC. HIV-uninfected persons experienced 179 ADC, 284 infection-related NADC, and 3418 infection-unrelated NADC. The rate ratio comparing HIV-infected and HIV-uninfected persons for ADC was 37.7 [95% confidence interval (CI): 31.7-44.8], with decreases in the rate ratio over time (P < 0.001). The rate ratio for infection-related NADC was 9.2 (95% CI: 7.7-11.1), also with decreases in the rate ratio over time (P < 0.001). These results were largely influenced by anal squamous cell cancer and Hodgkin's lymphoma. The rate ratio for infection-unrelated NADC was 1.3 (95% CI: 1.2-1.4), with no change in the rate ratio over time (P = 0.44). Among infection-unrelated NADCs, other anal, skin, other head and neck, and lung cancer rates were higher and prostate cancer rates lower in HIV-infected persons. Among all infection-unrelated NADCs, the rate ratio decreased over time only for lung cancer (P = 0.007). CONCLUSION: In comparison with those without HIV infection, HIV-infected persons are at particular risk for cancers with a known infectious cause, although the higher risk has decreased in the antiretroviral therapy era. Cancers without a known infectious cause are modestly increased in HIV-infected persons compared with HIV-uninfected persons.

BACKGROUND: Few studies have compared cancer risk between HIV-infected individuals and a demographically similar HIV-uninfected internal comparison group, adjusting for cancer risk factors. METHODS: We followed 20,775 HIV-infected and 215,158 HIV-uninfected individuals enrolled in Kaiser Permanente (KP) California for incident cancer from 1996 to 2008. Rate ratios (RR) were obtained from Poisson models comparing HIV-infected (overall and stratified by recent CD4 count and HIV RNA) with HIV-uninfected individuals, adjusted for age, sex, race/ethnicity, calendar period, KP region, smoking, alcohol/drug abuse, and overweight/obesity. RESULTS: We observed elevated RRs for Kaposi sarcoma (KS; RR = 199; P < 0.001), non-Hodgkin lymphoma (NHL; RR = 15; P < 0.001), anal cancer (RR = 55; P < 0.001), Hodgkin lymphoma (HL; RR = 19; P < 0.001), melanoma (RR = 1.8; P = 0.001), and liver cancer (RR = 1.8; P = 0.013), a reduced RR for prostate cancer (RR = 0.8; P = 0.012), and no increased risk for oral cavity/pharynx (RR = 1.4; P = 0.14), lung (RR = 1.2; P = 0.15), or colorectal (RR = 0.9; P = 0.34) cancers. Lung and oral cavity/pharynx cancers were elevated for HIV-infected subjects in models adjusted only for demographics. KS, NHL, anal cancer, HL, and colorectal cancer had significant (P < 0.05) trends for increasing RRs with decreasing recent CD4. The RRs for lung and oral cavity/pharynx cancer were significantly elevated with CD4 < 200 cells/μL and for melanoma and liver cancer with CD4 < 500 cells/μL. Only KS and NHL were associated with HIV RNA. CONCLUSION: Immunodeficiency was positively associated with all cancers examined except prostate cancer among HIV-infected compared with HIV-uninfected individuals, after adjustment for several cancer risk factors. IMPACT: Earlier antiretroviral therapy initiation to maintain high CD4 levels might reduce the burden of cancer in this population.

PURPOSE: To describe the epidemiology and risk factors for cardiovascular disease (CVD) in survivors of adolescent and young adult (AYA) cancer. METHODS: We identified a retrospective cohort of 2-year survivors of AYA cancer who were diagnosed between the ages of 15 to 39 years (1998 to 2009) at Kaiser Permanente Southern California. A comparison group without cancer was selected and matched 10:1 to cancer survivors on the basis of age, sex, Kaiser Permanente Southern California membership, and calendar year. Patients were followed through December 31, 2012, for coronary artery disease, heart failure, and stroke. Time-dependent Poisson regression was used to evaluate the effect that cancer survivorship had on the risk of developing CVD, adjusted for cardiovascular risk factors (CVRFs; ie, diabetes, hypertension, and dyslipidemia), ethnicity, smoking, and overweight/obesity. Among cancer survivors, mortality risk by CVD status was examined using Cox regression. RESULTS: A total of 5,673 2-year survivors of AYA cancer and 57,617 comparison patients were included, representing 24,839 and 239,073 person-years of follow-up, respectively. Overall, cancer survivors had more than two-fold risk of developing CVD (adjusted incidence rate ratio, 2.37; 95% CI, 1.93 to 2.93) when compared with patients without cancer; survivors of leukemia and breast cancer were at the highest risk (adjusted incidence rate ratio, 4.23; 95% CI, 1.73 to 10.31; and 3.63; 95% CI, 2.41 to 5.47, respectively) of developing CVD. Having any of the CVRFs increased the risk of CVD in cancer survivors. Cancer survivors who developed CVD had an 11-fold increased overall mortality risk (hazard ratio, 10.9; 95% CI, 8.1 to 14.8) when compared with survivors without CVD. CONCLUSION: Survivors of AYA cancer are at increased risk for developing CVD. Survival after CVD onset is compromised, and CVRFs are independent modifiers of CVD risk. These data form the basis for identifying high-risk individuals and proactive management of CVRFs.