Total-, LDL-, and HDL-cholesterol, apolipoproteins, and triglycerides with risk of total and fatal prostate cancer in Black and White men in the ARIC study.

BACKGROUND: Cholesterol reduction is considered a mechanism through which cholesterol-lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations between total cholesterol and more advanced stage and grade in White men, whether associations for total cholesterol, low (LDL)- and high (HDL)-density lipoprotein cholesterol, apolipoprotein B (LDL particle) and A1 (HDL particle), and triglycerides are similar for fatal prostate cancer and in Black men, who experience a disproportionate burden of total and fatal prostate cancer, is unknown. METHODS: We conducted a prospective study of 1553 Black and 5071 White cancer-free men attending visit 1 (1987-1989) of the Atherosclerosis Risk in Communities Study. A total of 885 incident prostate cancer cases were ascertained through 2015, and 128 prostate cancer deaths through 2018. We estimated multivariable-adjusted hazard ratios (HRs) of total and fatal prostate cancer per 1-standard deviation increments and for tertiles (T1-T3) of time-updated lipid biomarkers overall and in Black and White men. RESULTS: Greater total cholesterol concentration (HR per-1 SD = 1.25; 95% CI = 1.00-1.58) and LDL cholesterol (HR per-1 SD = 1.26; 95% CI = 0.99-1.60) were associated with higher fatal prostate cancer risk in White men only. Apolipoprotein B was nonlinearly associated with fatal prostate cancer overall (T2 vs. T1: HR = 1.66; 95% CI = 1.05-2.64) and in Black men (HR = 3.59; 95% CI = 1.53-8.40) but not White men (HR = 1.13; 95% CI = 0.65-1.97). Tests for interaction by race were not statistically significant. CONCLUSIONS: These findings may improve the understanding of lipid metabolism in prostate carcinogenesis by disease aggressiveness, and by race while emphasizing the importance of cholesterol control.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study.

BACKGROUND: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. OBJECTIVE: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. DESIGN: Cross-sectional study. SETTING: Four U.S. community-based epidemiologic cohort studies with mGFR. PATIENTS: 3223 participants in 4 studies. MEASUREMENTS: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. RESULTS: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR - eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. LIMITATION: Single measurement of mGFR and serum markers without short-term replicates. CONCLUSION: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. PRIMARY FUNDING SOURCE: National Institutes of Health.

Effect of antiretroviral therapy on allele-associated Lp(a) level in women with HIV in the Women's Interagency HIV Study.

We previously demonstrated an association between lipoprotein (a) [Lp(a)] levels and atherosclerosis in human immunodeficiency virus (HIV)-seropositive women. The effects of antiretroviral therapy (ART) on Lp(a) levels in relation to apo(a) size polymorphism remain unclear. ART effects on allele-specific apo(a) level (ASL), an Lp(a) level associated with individual apo(a) alleles within each allele-pair, were determined in 126 HIV-seropositive women. ART effects were tested by a mixed-effects model across pre-ART and post-ART first and third visits. Data from 120 HIV-seronegative women were used. The mean age was 38 years; most were African-American (∼70%). Pre-ART ASLs associated with the larger (4.6 mg/dl vs. 8.0 mg/dl, P = 0.024) or smaller (13 mg/dl vs. 19 mg/dl, P = 0.041) apo(a) sizes were lower in the HIV-seropositive versus HIV-seronegative group, as was the prevalence of a high Lp(a) level (P = 0.013). Post-ART ASL and prevalence of high Lp(a) or apo(a) sizes and frequency of small size apo(a) (22 kringles) did not differ between the two groups. ART increased Lp(a) level (from 18 to 24 mg/dl, P < 0.0001) and both ASLs (P < 0.001). In conclusion, regardless of genetic control, Lp(a) can be modulated by HIV and its treatment. ART initiation abrogates HIV-induced suppression of Lp(a) levels and ASLs, contributing to promote CVD risk in HIV-seropositive individuals.

The amyloidogenic V122I transthyretin variant in elderly black Americans.

BACKGROUND: Approximately 4% of black Americans carry a valine-to-isoleucine substitution (V122I) in the transthyretin protein, which has been associated with late-onset restrictive amyloid cardiomyopathy and increased risks of death and heart failure. METHODS: We determined genotype status for the transthyretin gene (TTR) in 3856 black participants in the Atherosclerosis Risk in Communities study and assessed clinical profiles, mortality, and the risk of incident heart failure in V122I TTR variant carriers (124 participants [3%]) versus noncarriers (3732 participants). Cardiac structure and function and features suggestive of cardiac amyloidosis were assessed in participants who underwent echocardiography during visit 5 (2011 to 2013), when they were older than 65 years of age. RESULTS: After 21.5 years of follow-up, we did not detect a significant difference in mortality between carriers (41 deaths, 33%) and noncarriers (1382 deaths, 37%; age- and sex-stratified hazard ratio among carriers, 0.99; 95% confidence interval [CI], 0.73 to 1.36; P=0.97). The TTR variant was associated with an increased risk of incident heart failure (age- and sex-stratified hazard ratio, 1.47; 95% CI, 1.03 to 2.10; P=0.04). On echocardiography at visit 5, carriers (46 participants) had worse systolic and diastolic function, as well as a higher level of N-terminal pro-brain natriuretic peptide, than noncarriers (1194 participants), although carriers had a low prevalence (7%) of overt manifestations of amyloid cardiomyopathy. CONCLUSIONS: We did not detect a significant difference in mortality between V122I TTR allele carriers and noncarriers, a finding that contrasts with prior observations; however, the risk of heart failure was increased among carriers. The prevalence of overt cardiac abnormalities among V122I TTR carriers was low. (Funded by the National Heart, Lung, and Blood Institute and others.).

Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

OBJECTIVE: In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. APPROACH AND RESULTS: The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level (P=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4+ T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) (P=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. CONCLUSIONS: Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection.

Not Just Another "Found Down": Concomitant Upper Arm and Gluteal Compartment Syndrome.

BACKGROUND: Compartment syndrome is often considered in patients with long-bone fractures and soft-tissue injuries, but is not as commonly associated with a period of unconsciousness. CASE REPORT: A 65-year-old man was brought to our emergency department (ED) because he had lost consciousness for an unknown amount of time after snorting heroin. He had severe pain in his upper right arm. Physical examination revealed right arm edema, paresthesia, tenderness, and firmness to palpation. During the ED assessment, the patient began to experience pain in his right hip to a degree exceeding examination findings. We considered compartment syndrome affecting his upper arm as well as his gluteal muscles. The patient was taken to the operating room for fasciotomy. The triceps muscle was found to be bulging out of the compartment, demonstrating advanced compartment syndrome. A posterior approach to the hip allowed the gluteal sling and the fascia to be released, eliminating tension on the gluteus medius/minimus and gluteus maximus compartments. With physical therapy, the patient regained full flexion and extension in his arm at the elbow, partial extension of his wrist, and range of motion and strength in his hip. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: If not recognized, compartment syndrome can jeopardize limb and life. It should be considered in patients experiencing inordinate pain, especially if they were found unconscious at the incident scene. Pressure-induced ischemia can impair muscle function within hours. If it is not relieved with fasciotomy, the patient can sustain irreversible functional loss.

Last but not least: PA practice in Mississippi.

This article describes the history of physician assistants (PAs) in Mississippi, the last state to pass legislation allowing for PA practice. A small group of PAs in the state began pursuing a PA practice act in the early 1990s with little political advocacy experience, and in 1994, the American Academy of PAs actively joined "The Battle for Mississippi." In April 2000, after years of PA advocacy, Mississippi passed the bill that would authorize PA practice in the state.

Three PAs talk about success in Mississippi.

This article gives the first-hand perspectives of three physician assistants (PAs) involved in the profession's years of struggle to gain practice authority in Mississippi. Through a series of questions and answers, each PA describes his or her part in the historical events that made Mississippi the final US state to regulate PAs.

Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study.

BACKGROUND: Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored. OBJECTIVE: To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs). DESIGN: Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study. SETTING: Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995. PARTICIPANTS: 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years. MEASUREMENTS: Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models. RESULTS: Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]). LIMITATION: Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes. CONCLUSION: Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Ankle-Brachial Index and Risk of Sudden Cardiac Death in the Community: The ARIC Study.

BACKGROUND: Sudden cardiac death (SCD) is a significant global public health problem accounting for 15% to 20% of all deaths. A great majority of SCD is associated with coronary heart disease, which may first be detected at autopsy. The ankle-brachial index (ABI) is a simple, noninvasive measure of subclinical atherosclerosis. The purpose of this study was to examine the relationship between ABI and SCD in a middle-aged biracial general population. METHODS AND RESULTS: Participants of the ARIC (Atherosclerosis Risk in Communities) study with an ABI measurement between 1987 and 1989 were included. ABI was categorized as low (≤0.90), borderline (0.90-1.00), normal (1.00-1.40), and noncompressible (>1.40). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual and was adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Cox proportional hazards models were used to evaluate the associations between baseline ABI and incident SCD. Of the 15 081 participants followed for a median of 23.5 years, 556 (3.7%) developed SCD (1.96 cases per 1000 person-years). Low and borderline ABIs were associated with an increased risk of SCD (demographically adjusted hazard ratios [HRs], 2.27 [95% CI, 1.64-3.14] and 1.52 [95% CI, 1.17-1.96], respectively) compared with normal ABI. The association between low ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors (HR, 1.63 [95% CI, 1.15-2.32]). CONCLUSIONS: Low ABI is independently associated with an increased risk of SCD in a middle-aged biracial general population. ABI could be incorporated into future SCD risk prediction models.

Association of Segment-Specific Pulse Wave Velocity With Vascular Calcification: The ARIC (Atherosclerosis Risk in Communities) Study.

BACKGROUND: Pulse wave velocity (PWV) is a noninvasive measure of arterial stiffness and predictor of cardiovascular disease. However, the association between PWV and vascular calcification across different vascular beds has not been fully investigated. This study aimed to quantify the association between PWV and multiterritory calcification and to explore whether PWV can identify individuals with vascular calcification beyond traditional risk factors. METHODS AND RESULTS: Among 1351 older adults (mean age, 79.2 years [SD, 4.1]) from the ARIC (Atherosclerosis Risk in Communities) study, we measured segment-specific PWVs: heart-carotid, heart-femoral, carotid-femoral, heart-ankle, brachial-ankle, and femoral-ankle. Dependent variables were high calcium score (≥75th percentile of Agatston score) across different vascular beds: coronary arteries, aortic valve ring, aortic valve, mitral valve, ascending aorta, and descending aorta. Quartiles of carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV were significantly associated with coronary artery calcium (eg, adjusted odds ratio [OR] for the highest versus lowest quartile of carotid-femoral PWV, 1.84 [95% CI, 1.24-2.74]). Overall, PWVs were most strongly associated with descending aorta calcification, with significant results for carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV (eg, adjusted OR for the highest versus lowest quartile of carotid-femoral PWV, 3.99 [95% CI, 2.61-6.17]). In contrast, femoral-ankle PWV was inversely associated with descending aorta calcification. Some PWVs improved the discrimination of coronary artery calcium and descending aorta calcification beyond traditional risk factors. CONCLUSIONS: The associations of PWV with vascular calcification varied substantially across segments, with descending aorta calcification most closely linked to PWVs. Our study suggests that some PWVs, especially carotid-femoral PWV, are helpful to identify individuals with coronary artery calcium and descending aorta calcification.

Associations between factors affecting access to care and health-related quality of life: results of a statewide HIV/AIDS cross-sectional study.

The objective of this cross-sectional study was to describe the relationship between access to care and health-related quality of life (HRQOL) for persons living with HIV/AIDS (PLWHA) in Mississippi by administering a statewide survey. A random probability sample of PLWHA was derived from the Mississippi State Department of Health's communicable disease tracking system. Interviews were conducted with 220 PLWHA to collect data on access to care, demographic and social characteristics, and HRQOL. Overall, most participants had access to care and reasonable HRQOL. Multivariate and univariate analyses were performed to measure associations between access to care and HRQOL. Univariate analyses showed that age, income, social networks, severity of disease, having been prescribed medications, and having experienced problems accessing care to be significantly associated with HRQOL scales. Multivariate analysis of variance models further demonstrated low-income level, having experienced problems accessing care, and having been prescribed antiretroviral medications to be significantly associated with HRQOL. Reducing barriers is a major factor in improving quality of life. This study provides needed insight into the relationship between access to care and HRQOL among PLWHA in Mississippi, which could be valuable to public health planners to help them better understand how to make the greatest impact on HRQOL.

Determining unmet, adequately met, and overly met needs for health care and services for persons living with HIV/AIDS in Mississippi.

A statewide needs assessment of persons living with HIV/AIDS (PLWHA) was conducted to determine what is known about access to care, utilization of services, and perceived barriers to receiving care and services. Our objective was to determine which needs were being met or unmet among PLWHA in Mississippi to provide a better understanding of how effectively to allocate funding to provide for the needs of that group. In this cross-sectional study, a true random sample of PLWHA in Mississippi was interviewed in 2005-2006. Questions were asked to identify opinions about respondents' experiences with 23 health care services and 30 public or private assistance services. The kappa statistic was used to measure agreement between level of services needed and level of services provided. Services with the lowest kappa scores revealed which services were being either mostly unmet, or even overly met. Greatest service needs were HIV viral load test, Pap smear, CD4/T-cell count test, and medication for HIV/AIDS, which were reasonably well met. The most significantly unmet needs were dental care and dental exams, eye care and eye exams, help paying for housing, subsidized housing assistance, mental health therapy or counseling, access to emotional support groups, and job placement or employment. Overly met services included medical care at a physician's office or clinic and free condoms. This study identified needs perceived to be significantly unmet by PLWHA, as well as areas that were perceived to be adequately or overly met. This information may be used to target areas with the greatest impact for improvement and provide insight into how to effectively allocate health care resources and public/private assistance.

Severe cardiotoxicity associated with ixabepilone use in metastatic breast cancer.

OBJECTIVE: To report a case of cardiogenic shock and fulminant heart failure associated with a single dose of ixabepilone. CASE SUMMARY: A 32-year-old woman presented to the emergency department (ED) with abdominal pain and difficulty breathing within 1 hour after receiving a partial dose of ixabepilone (26 mg/m(2)) at an oncologist's office. She had breast cancer, with metastases to the bone and liver and evidence of early liver failure. While in the ED, she developed acute respiratory failure requiring intubation. Bedside ultrasound imaging showed free abdominal fluid. Computed tomography (CT) scans showed evidence of right-sided heart failure and abdominal fluid consistent with ascites but no evidence of pulmonary embolism. After the CT scan, the patient experienced pulseless electrical activity cardiac arrest. All attempts at resuscitation were unsuccessful. DISCUSSION: Ixabepilone is a novel drug for treatment of advanced breast cancer. The most commonly reported adverse effects are peripheral neuropathies and hematologic issues such as neutropenia. To our knowledge, this is the first detailed report of a severe adverse cardiac event associated with ixabepilone use. Many other chemotherapeutic agents have cardiotoxic effects. An objective causality assessment, using the Naranjo probability scale, revealed that an adverse drug event was probable. CONCLUSIONS: Clinicians should maintain broad differential diagnoses that include adverse reactions to drugs relatively new to the market. Ixabepilone may have cardiotoxic effects that necessitate further study, particularly when the drug is administered after cardiotoxic chemotherapy.

Racial Differences in Fatal Out-of-Hospital Coronary Heart Disease and the Role of Income in the Atherosclerosis Risk in Communities Cohort Study (1987 to 2017).

Black patients have higher incident fatal coronary heart disease (CHD) rates than do their White counterparts. Racial differences in out-of-hospital fatal CHD could explain the excess risk in fatal CHD among Black patients. We examined racial disparities in in- and out-of-hospital fatal CHD among participants with no history of CHD, and whether socioeconomic status might play a role in this association. We used data from the ARIC (Atherosclerosis Risk in Communities) study, including 4,095 Black and 10,884 White participants, followed between 1987 and 1989 until 2017. Race was self-reported. We examined racial differences in in- and out-of-hospital fatal CHD with hierarchical proportional hazard models. We then examined the role of income in these associations, using Cox marginal structural models for a mediation analysis. The incidence of out-of-hospital and in-hospital fatal CHD was 1.3 and 2.2 in Black participants, and 1.0 and 1.1 in White participants, respectively, per 1,000 person-years. The gender- and age-adjusted hazard ratios comparing out-of-hospital and in-hospital incident fatal CHD in Black with that in White participants were 1.65 (1.32 to 2.07) and 2.37 (1.96 to 2.86), respectively. The income-controlled direct effects of race in Black versus White participants decreased to 1.33 (1.01 to 1.74) for fatal out-of-hospital and to 2.03 (1.61 to 2.55) for fatal in-hospital CHD in Cox marginal structural models. In conclusion, higher rates of fatal in-hospital CHD in Black participants than in their White counterparts likely drive the overall racial differences in fatal CHD. Income largely explained racial differences in both fatal out-of-hospital CHD and fatal in-hospital CHD.

Kidney function, bone-mineral metabolism markers, and calcification of coronary arteries, aorta, and cardiac valves in older adults.

BACKGROUND AND AIMS: The contribution of kidney dysfunction, especially at mild-to-moderate stages, and bone-mineral metabolism (BMM) markers to vascular calcification remains controversial or unclear. We comprehensively evaluated the association of kidney and BMM markers with coronary artery calcification (CAC) and extra-coronary calcification (ECC). METHODS: In 1931 ARIC participants (age 73-95 years) without coronary heart disease at visit 7 (2018-19), we investigated the associations of estimated glomerular filtration rate (eGFR) (with creatinine, cystatin C, and both) and five serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) with high CAC and ECC (sex-race specific ≥75th vs. <75th percentile Agatston score) or any vs. zero CAC and ECC using multivariable logistic regression. For eGFR and BMM markers, we took their weighted cumulative averages from visit 1 (1987-89) to visit 5 (2011-13). RESULTS: Lower eGFR, regardless of equations used, was not robustly associated with high CAC or ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed robust associations with high CAC (only when modeled continuously) and ECC, independently of kidney function (e.g., odds ratio 1.94 [95%CI 1.38-2.73] for high aortic valve calcification, in the highest vs. lowest quartile). Results were generally consistent when analyzing any CAC or ECC, although cystatin C-based eGFR <60 mL/min/1.73 m2 became significantly associated with mitral valve calcification (odds ratio 1.69 [1.10-2.60]). CONCLUSIONS: Among kidney and BMM measures tested, only serum phosphorus demonstrated robust associations with both CAC and ECC, supporting a key role of phosphorus in the pathophysiology of vascular calcification.

Blood Pressure, Hypertension, and Antihypertensive Medication Use and Risk of Total and Fatal Prostate Cancer in Black and White Men in the Atherosclerosis Risk in Communities (ARIC) Study.

Black men are disproportionately burdened by hypertension and prostate cancer (PCa), and some cohorts suggest hypertension is associated with increased PCa risk. We investigated the association of hypertension and antihypertensive use with total (N = 889; 290 Black, 599 White) and fatal (N = 127; 42 Black, 85 White) PCa risk in 6658 (1578 Black, 5080 White) men in the Atherosclerosis Risk in Communities study. In adjusted Cox models, time-updated untreated stage 1 hypertension (systolic/diastolic blood pressure 130-139/80-89 mmHg) was associated with a higher risk of fatal PCa compared to untreated normal blood pressure (hazard ratio (HR) = 1.95; 95% confidence interval (CI) = 1.03-3.70). Compared to untreated normal/elevated blood pressure (combined given few events in those with untreated normal blood pressure), the association was significant in Black (HR = 3.35; 95% CI = 1.27-8.83), but not White (HR = 1.21; 95% CI = 0.58-2.55) men. Ever antihypertensive use was associated with a lower risk of fatal PCa compared to never use (HR = 0.52; 95% CI = 0.31-0.87), including short-term (< 10 years) and long-term (310 years) use (p-trend = 0.02) with similar inverse associations in Black and White men. Hypertension and antihypertensive use were not significantly associated with total PCa. The positive association of untreated stage 1 hypertension and fatal PCa warrants additional confirmation, especially in Black men, and characterization of the underlying mechanism.

Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer.

BACKGROUND: Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer. METHODS: African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histology-based precancer (CIN3+) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry. RESULTS: Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes. CONCLUSIONS: Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression. IMPACT: Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.

Pulmonary function and left ventricular mass in African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

PURPOSE: Impaired pulmonary function has been associated with increased cardiovascular disease incidence and mortality. The objective of this study was to investigate associations between pulmonary function and left ventricular (LV) mass. METHODS: Participants were African American women (n = 1,069) and men (n = 555) aged 49-73 years, from the Atherosclerosis Risk in Communities study. Mean pulmonary function values at the first (1987-1989) and second (1990-1992) examinations were used. Echocardiograms were performed at the third and early in the fourth examinations (1993-1996). Analysis of covariance and linear regression were used to assess associations. RESULTS: Mean levels of LV mass decreased with increasing quintiles of forced expiratory volume in one second (FEV(1) ) among female never smokers (P = 0.039). Forced vital capacity (FVC) showed stronger associations than FEV(1) with LV mass. Among men, LV mass was positively associated with FEV(1) among current and never smokers, and with FVC among never smokers. Additional analyses among never smokers revealed significant inverse associations between LV mass and FVC among women with waist-to-hip ratios of >0.85 and those with no history of diabetes. In contrast, significant positive associations between LV mass and FVC were seen among male never smokers with body mass index (BMI) of ≤24.9 kg/m(2) , waist-to-hip ratios of ≤0.95, no history of hypertension or diabetes, and ≤60 years old. BMI and waist-to-hip ratio significantly modified associations among men. CONCLUSIONS: Among never smokers, LV mass and pulmonary function were inversely associated among women and positively associated among men. Further studies are warranted.

The Physiologically Difficult Intubation.

Emergency physicians intubate critically ill patients almost daily. Intubation of the critically ill emergency department (ED) patient is a high-risk, high-stress situation, as many have physiologic derangements such as hypotension, hypoxemia, acidosis, and right ventricular dysfunction that markedly increase the risk of peri-intubation cardiovascular collapse and cardiac arrest. This chapter discusses critical pearls and pitfalls to intubate the critically ill ED patient with physiologic derangements. These pearls and pitfalls include appropriate preoxygenation; circulatory resuscitation; proper patient position and room setup; selection of medications for rapid sequence intubation; and intubation of patients with severe acidosis, traumatic brain injury, and pulmonary hypertension.