Kevin L. Kraemer

HIV Infection and the Risk of Acute Myocardial Infarction

IMPORTANCE Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded. OBJECTIVE To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care. DESIGN AND SETTING Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009. PARTICIPANTS After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI. MAIN OUTCOME MEASURE Acute myocardial infarction. RESULTS We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66). CONCLUSIONS AND RELEVANCE Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.

HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation

BACKGROUND Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)-infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS). METHODS Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities. RESULTS HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14-2.09; OR, 2.25; 95% CI, 1.60-3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44-2.71, OR, 1.68; 95% CI, 1.22-2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64-4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions. CONCLUSIONS These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.

Text‐Message‐Based Drinking Assessments and Brief Interventions for Young Adults Discharged from the Emergency Department

BACKGROUND Brief interventions have the potential to reduce heavy drinking in young adults who present to the emergency department (ED), but require time and resources rarely available. Text-messaging (TM) may provide an effective way to collect drinking data from young adults after ED discharge as well as to provide immediate feedback and ongoing support for behavior change. The feasibility of screening young adults in the ED, recruiting them for a TM-based interventional trial, collecting weekly drinking data through TM, and the variance in drinking outcomes remains unknown. METHODS Young adults in 3 urban EDs (n = 45; aged 18 to 24 years, 54% women) identified as hazardous drinkers by the Alcohol Use Disorders Identification Test-Consumption score were randomly assigned to weekly TM-based feedback with goal setting (Intervention), weekly TM-based drinking assessments without feedback (Assessment), or control. Participants in the Intervention group who reported ≥5 (for men) and ≥4 (for women) maximum drinks during any one 24-hour period were asked whether they would set a goal to reduce their drinking the following week. We describe the interaction with TM and goal setting. We also describe the heavy drinking days (HDDs), drinks per drinking day (DPDD) using timeline follow-back procedure at baseline and 3 months. RESULTS We screened 109 young adults over 157 hours across 24 unique days and 52 (48%; 95% CI 38 to 50) screened positive for hazardous drinking. Of these, 45 (87%; 95% CI 74 to 94) met inclusion criteria, were enrolled and randomized, and 6 (13%; 95% CI 5 to 27) did not complete 3-month web-based follow-up; 88% (95% CI 84 to 91) of weekly TM-based drinking assessments were answered, with 77% (95% CI 58 to 90) of participants responding to all 12 weeks. Agreeing to set a goal was associated with a repeat HDD 36% (95% CI 17 to 55) of the time compared with 63% (95% CI 44 to 81) when not willing to set a goal. At 3 months, participants that were exposed to the TM-based intervention had 3.4 (SD 5.4) fewer HDDs in the last month and 2.1 (SD 1.5) fewer DPDD when compared to baseline. CONCLUSIONS TM can be used to assess drinking in young adults and can deliver brief interventions to young adults discharged from the ED. TM-based interventions have the potential to reduce heavy drinking among young adults but larger studies are needed to establish efficacy.

An empirical investigation of the factor structure of the AUDIT

This study investigated the Alcohol Use Disorders Identification Tests (AUDIT) factor structure and psychometric properties. The factor structure was derived from a sample of 7,035 men and women primary care patients. A principal components analysis identified 2 factors in the AUDIT data and was supported in a confirmatory factor analysis (CFA). The 2 factors were Dependence/Consequences and Alcohol Consumption. The CFA also provided support for a 3-factor model whose factors (Alcohol Consumption, Alcohol Dependence, and Related Consequences) matched those proposed by the AUDITs developers. Psychometric indexes were determined by use of the baseline and 12-month follow-up data of 301 men and women who entered a clinical trial. The results showed that the 2 factors had good reliability. Validity tests supported the interpretation of what the 2 factors measure, its implications for relationships to other variables, and the comparability of the 2- and 3-factor models.

Brief intervention for medical inpatients with unhealthy alcohol use: a randomized, controlled trial

Context Brief interventions reduce alcohol use in outpatients who drink unhealthy amounts but are not alcohol-dependent. Their effect in medical inpatients is unknown. Contribution The authors screened all adult medical inpatients at an urban teaching hospital and randomly assigned 341 risky drinkers to a 30-minute motivational counseling intervention followed gy treatment planning or to usual care. By 3 months, the same proportion of patients from both groups had received alcohol assistance, and both groups had reduced their drinking to the same degree. Cautions Three quarters of the participants met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence. Implications In this well-done study, brief intervention did not affect alcohol-related outcomes in persons who drank unhealthy amounts. The Editors Professional organizations recommend that clinicians screen their patients for unhealthy alcohol use (that is, the spectrum from drinking risky amounts to dependence) and conduct a brief intervention when indicated (1, 2). Despite this recommendation and the existence of brief, valid screening tools (35), patients with unhealthy alcohol use often are not identified and do not receive timely care. Although widely recommended, brief intervention has proven efficacy in decreasing alcohol consumption and related consequences only in unhealthy drinkers without alcohol dependence and in outpatient settings (6). Its efficacy among other populations (for example, persons with alcohol dependence) and in inpatient settings remains unclear (7). Evidence suggests, however, that medical inpatientsa group with a high prevalence of alcohol-related problemsmay benefit from brief intervention. Some studies have demonstrated the efficacy of brief intervention in settings similar to medical services in which alcohol-related problems are common and their related consequences are severe (8, 9). Further, brief interventions are well suited to medical services. Patients who otherwise might not seek care are accessible and have time for an intervention. Persons admitted because of an alcohol-related problem may recognize the link between drinking and hospitalization, thus providing a teachable moment (10). Also, busy staff might implement a brief intervention because of its brevity and flexibility. The unmet need for alcohol screening and intervention and opportunities for implementation underscore the importance of determining the efficacy of brief intervention in medical inpatients with unhealthy alcohol use. In addition, evaluating its effectiveness and practicality in real-world settings is critical to help clinicians make informed decisions when treating their patients (11). Therefore, we conducted a randomized, controlled trial to examine whether screening followed by brief intervention would improve alcohol-related outcomes in typical medical inpatients (that is, a racially diverse group with a range of unhealthy alcohol use, comorbid conditions, and readiness to change). We hypothesized that screening and brief intervention would lead to the following: receipt of alcohol assistance (for example, specialty treatment) among persons with alcohol dependence and, among all persons decreased alcohol consumption, alcohol-related problems, and health care utilization and improved readiness to change and health-related quality of life. Methods Patients As previously described, we recruited patients from the inpatient medical service of a large, urban teaching hospital (12). Trained research associates approached all patients who were age 18 years or older and whose physicians did not decline patient contact. Patients fluent in English or Spanish who gave verbal consent were asked to complete a screening interview to determine eligibility: currently (past month) drinking risky amounts (defined for eligibility as >14 standard drinks/wk or 5 drinks/occasion for men and >11 drinks/wk or 4 drinks/occasion for women and persons 66 years); 2 contacts to assist with follow-up; no plans to move from the area in the next year; and a Mini-Mental State Examination score of 21 or greater (13, 14). Research associates assessed demographic characteristics and administered the Alcohol Use Disorders Identification Test (AUDIT) (15) by interview. To better characterize current alcohol use, they assessed the average numbers of drinking-days per week and drinks consumed on a typical day, and the maximum number of drinks consumed per occasion (16, 17). For the first 7 months of the study, research associates asked these additional questions only to patients with an AUDIT score of 8 or greater (a recommended cutoff for screening) (18). For the remaining 22 months, research associates asked the additional questions to anyone who drank in the past 12 months to maximize identification of drinkers of risky amounts. Lastly, the research associates asked all patients who were drinking risky amounts to describe their readiness to change by using a visual analog scale ranging from 0 to 10 (19). Enrolled patients provided written informed consent and were compensated for each completed interview. The institutional review board at Boston University Medical Center approved this study. We secured additional privacy protection with a certificate of confidentiality from the National Institute on Alcohol Abuse and Alcoholism. Assessment at Enrollment Research associates interviewed patients before randomization to assess the characteristics shown in Table 1. One author reviewed the medical records to determine medical diagnoses (29). Diagnoses of alcohol use disorders were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (30), and were determined with the Composite International Diagnostic Interview (CIDI) Alcohol Module (31, 32). Table 1. Characteristics at Enrollment of All Study Patients and of the Subgroup with Alcohol Dependence* Randomization and Intervention An off-site data management group generated assignments to control and intervention groups by using a permuted block (size 8) randomization procedure stratified by AUDIT score (<12 vs. 12) and provided us the assignments in sealed opaque envelopes. We used the AUDIT score to stratify because we could not score the CIDI before randomization. After each baseline assessment, research associates opened an envelope and informed the patient of his or her assignment. Patients in the control group received usual care (that is, they were told the screening results and that they could discuss their drinking with their physicians). Specialists were available by referral. Systematic alcohol screening and brief intervention were not routine at this hospital. We assigned patients in the intervention group to a 30-minute session of brief motivational counseling (19, 33) conducted by counseling and clinical psychology doctoral students whom we trained and supervised. Sessions were audiotaped and included feedback, an open discussion, and construction of a change plan (Appendix). Outcomes and Measurements The first primary outcome was self-reported receipt of alcohol assistance in the past 3 months by patients with CIDI-determined alcohol dependence. This outcome was measured at the 3-month follow-up visit with a standardized interview based on the Treatment Services Review (34) and Form 90 (35). Assistance included residential treatment, outpatient treatment (for example, specialty counseling or therapy), medications, employee assistance programs, or mutual-help groups (for example, Alcoholics Anonymous). The other primary outcome was the change in the number of mean drinks per day in the past 30 days from enrollment to 12 months among all patients. We determined consumption with the Timeline Follow-back method (36). Five secondary consumption outcomes (past 30 days) included changes from enrollment to 12 months in the numbers of heavy drinking episodes (5 drinks/occasion for men and 4 drinks/occasion for women and for persons 66 y) and days abstinent; and the proportions of patients drinking risky amounts (>14 drinks/wk or 5 drinks/occasion for men and >7 drinks/wk or 4 drinks/occasion for women and persons 66 y) (37), having 1 or more heavy drinking episodes, and abstaining for all 30 days. Other secondary outcomes included the changes at 12 months in readiness to change (Taking Steps scale on the Stages of Change Readiness and Treatment Eagerness Scale) (38), alcohol problems (total score on the Short Inventory of Problems) (39), physical and mental health-related quality of life (Physical and Mental Component Summary scale scores on the Short-Form Health Survey) (40), and emergency department visits and days of medical hospitalization (both determined by a standardized interview based on the Treatment Services Review and Form 90) (34, 35). Follow-up Procedures Research associates conducted follow-up visits, which included reassessment of most domains covered at enrollment, usually in person and at 3 and 12 months (10% and 13%, respectively, by telephone; similar by randomized group). They performed alcohol breath tests at in-person follow-up visits (41). Although they were involved in the randomization assignment, research associates were not involved in the intervention. Further, 64% of patients at 3-month follow-up and 85% of patients at 12-month follow-up were interviewed by a different research associate than at baseline. Statistical Analysis We analyzed all patients in the groups to which they were randomly assigned. Reported P values are 2-tailed and are considered statistically significant if they were less than 0.05. We analyzed data with SAS/STAT software, versions 8.2 and 9.1.3 (SAS Institute, Inc., Cary, North Carolina). To describe the study sample and to compare groups, we used the chi-square test, Fisher exact test, 2-sample t test, and Wilcoxon rank-sum test, as appropriate. For the primary analyses, we used logistic and linear

Abdominal Aortic Aneurysms, Increasing Infrarenal Aortic Diameter, and Risk of Total Mortality and Incident Cardiovascular Disease Events 10-Year Follow-Up Data From the Cardiovascular Health Study

Background— Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse. Methods and Results— In 1992 to 1993, 4734 Cardiovascular Health Study participants ≥65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter ≥3.0 cm or an infrarenal/suprarenal ratio ≥1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation ≥3 cm identified 68% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4% of the total population and that a ≥2.5-cm dilation identified 91% of all AAA repairs and 9 of the 10 deaths in 10% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95% confidence interval 1.25 to 1.85). Compared with diameters <2.0 cm, infrarenal aortic diameters 2.0 to <3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men. Conclusions— This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters >2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.

The Risk of Incident Coronary Heart Disease Among Veterans With and Without HIV and Hepatitis C

Background—Whether hepatitis C virus (HCV) confers additional coronary heart disease (CHD) risk among human immunodeficiency virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured. Methods and Results—We analyzed data on 8579 participants (28% HIV+, 9% HIV+HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from January 2000 to July 2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV−HCV− Veterans, HIV+HCV+ Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio, 2.03; 95% confidence interval, 1.28 to 3.21) or a competing risk (adjusted HR, 2.45; 95% confidence interval, 1.83 to 3.27 respectively). Compared with HIV+HCV− Veterans, HIV+HCV+ Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted hazard ratio, 1.93; 95% confidence interval, 1.02 to 3.62) or a competing risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.03 to 2.07). Conclusions—HIV+HCV+ Veterans have an increased risk of CHD compared with HIV+HCV− and HIV−HCV− Veterans.

Comparison of Consumption Effects of Brief Interventions for Hazardous Drinking Elderly

We sought to determine if Brief Interventions [BIs, Motivational Enhancement (ME), and Brief Advice (BA)] reduced alcohol consumption among hazardous alcohol drinking elderly (65 years or older) and whether the elderly responded similarly to younger populations. In 12 primary care offices from 10 1995 to 12 1997, we screened 13,438 patients of whom 2702 were elderly (180 were hazardous drinkers). Forty-five elderly enrollees were randomized to receive ME (n = 18), BA (n = 12), and Standard Care (SC, n = 12). At baseline, the elderly drank more alcohol and abstained fewer days than the younger cohort (p<0.05). During the year, the elderly in ME, BA, and SC intervention arms increased the number of days abstained, decreased the number of drinks per day, and reduced the number of total days per month drinking. There were trends toward decreases in the alcohol consumption measures in the ME and BA treatment arms compared to SC. The elderlys response to all interventions was similar to that of the younger cohort. This study suggests that hazardous alcohol consumption in the elderly is common and that BIs reduce alcohol consumption in the elderly similar to younger populations.

Screening and Identification of Older Adults with Alcohol Problems in Primary Care

Primary care physicians can anticipate encountering more elderly patients with alcohol problems since this population is increasing and the prevalence of alcohol problems has been stable. Brief screening tools, originally developed and validated among younger adults, may not be appropriate in the elderly. Therefore, specific validation studies and the development of elderly specific instruments have been reported. The specific goals of this report are to (1) review available screening tools for alcohol problems, (2) summarize elderly focused studies, and (3) provide recommendations for use in primary care. Using a variety of standards, the CAGE (Cut down, Annoyed, Guilty, and .Eye opener) is the most consistent brief screen, but its threshold may need to be adjusted in the elderly. The Michigan Alcoholism Screening Test-Geriatric Version includes elderly-specific consequences, but its length may hinder routine use even in shortened form. Finally, the Alcohol Use Disorders Identification Test, although less sensitive than the CAGE, can also capture problem drinkers. Efforts are needed to include elderly-specific consequences and meaningful consumption thresholds in a brief, easily applied screen.

HIV status and the risk of ischemic stroke among men

Objective: Given conflicting data regarding the association of HIV infection and ischemic stroke risk, we sought to determine whether HIV infection conferred an increased ischemic stroke risk among male veterans. Methods: The Veterans Aging Cohort Study–Virtual Cohort consists of HIV-infected and uninfected veterans in care matched (1:2) for age, sex, race/ethnicity, and clinical site. We analyzed data on 76,835 male participants in the Veterans Aging Cohort Study–Virtual Cohort who were free of baseline cardiovascular disease. We assessed demographics, ischemic stroke risk factors, comorbid diseases, substance use, HIV biomarkers, and incidence of ischemic stroke from October 1, 2003, to December 31, 2009. Results: During a median follow-up period of 5.9 (interquartile range 3.5–6.6) years, there were 910 stroke events (37.4% HIV-infected). Ischemic stroke rates per 1,000 person-years were higher for HIV-infected (2.79, 95% confidence interval 2.51–3.10) than for uninfected veterans (2.24 [2.06–2.43]) (incidence rate ratio 1.25 [1.09–1.43]; p < 0.01). After adjusting for demographics, ischemic stroke risk factors, comorbid diseases, and substance use, the risk of ischemic stroke was higher among male veterans with HIV infection compared with uninfected veterans (hazard ratio 1.17 [1.01–1.36]; p = 0.04). Conclusions: HIV infection is associated with an increased ischemic stroke risk among HIV-infected compared with demographically and behaviorally similar uninfected male veterans.