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Objectives: Predictors of chronic kidney disease (CKD) amongst HIV-positive persons are well established, but insights into the prognosis after CKD including the role of modifiable risk factors are limited., Design: Prospective cohort study., Methods: D:A:D participants developing CKD (confirmed, >3 months apart, eGFR ≤ 60 ml/min per 1.73 m or 25% eGFR decrease when eGFR ≤ 60 ml/min per 1.73 m) were followed to incident serious clinical events (SCE); end stage renal and liver disease (ESRL and ESLD), cardiovascular disease (CVD), AIDS-defining and non-AIDS-defining malignancies (NADM), other AIDS or death, 6 months after last visit or 1 February 2016. Poisson regression models considered associations between SCE and modifiable risk factors., Results: During 2.7 (IQR 1.1-5.1) years median follow-up 595 persons with CKD (24.1%) developed a SCE [incidence rate 68.9/1000 PYFU (95% confidence interval 63.4-74.4)] with 8.3% (6.9-9.0) estimated to experience any SCE at 1 year. The most common SCE was death (12.7%), followed by NADM (5.8%), CVD (5.6%), other AIDS (5.0%) and ESRD (2.9%). Crude SCE ratios were significantly higher in those with vs. without CKD, strongest for ESRD [65.9 (43.8-100.9)] and death [4.8 (4.3-5.3)]. Smoking was consistently associated with all CKD-related SCE. Diabetes predicted CVD, NADM and death, whereas dyslipidaemia was only significantly associated with CVD. Poor HIV-status predicted other AIDS and death, eGFR less than 30 ml/min per 1.73 m predicted CVD and death and low BMI predicted other AIDS and death., Conclusion: In an era where many HIV-positive persons require less monitoring because of efficient antiretroviral treatment, persons with CKD carry a high burden of SCE. Several potentially modifiable risk factors play a central role for CKD-related morbidity and mortality.

Background: People living with HIV (PLWH) experience a higher cardiovascular disease (CVD) risk. Yet, traditional algorithms are often used to estimate CVD risk. We evaluated the performance of 4 commonly used algorithms., Setting: The Netherlands., Methods: We used data from 16,070 PLWH aged ≥18 years, who were in care between 2000 and 2016, had no pre-existing CVD, had initiated first combination antiretroviral therapy >1 year ago, and had available data on CD4 count, smoking status, cholesterol, and blood pressure. Predictive performance of 4 algorithms [Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D); Systematic COronary Risk Evaluation adjusted for national data (SCORE-NL); Framingham CVD Risk Score (FRS); and American College of Cardiology and American Heart Association Pooled Cohort Equations (PCE)] was evaluated using a Kaplan-Meier approach. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed using observed-versus-expected ratios, calibration plots, and Greenwood-Nam-D'Agostino goodness-of-fit tests., Results: All algorithms showed acceptable discrimination (Harrell's C-statistic 0.73-0.79). On a population level, D:A:D, SCORE-NL, and PCE slightly underestimated, whereas FRS slightly overestimated CVD risk (observed-versus-expected ratios 1.35, 1.38, 1.14, and 0.92, respectively). D:A:D, FRS, and PCE best fitted our data but still yielded a statistically significant lack of fit (Greenwood-Nam-D'Agostino χ ranged from 24.57 to 34.22, P < 0.05). Underestimation of CVD risk was particularly observed in low-predicted CVD risk groups., Conclusions: All algorithms perform reasonably well in PLWH, with SCORE-NL performing poorest. Prediction algorithms are useful for clinical practice, but clinicians should be aware of their limitations (ie, lack of fit and slight underestimation of CVD risk in low-risk groups).

Objectives: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM)., Methods: We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional sample of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged ≥ 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities., Results: Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2%; stroke, 7.5 versus 4.2%; thrombosis, 10.5 versus 4.2%; and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99; P = 0.03] and thrombosis (aOR 2.87; P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM; P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score., Conclusions: HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population., (© 2018 British HIV Association.)

Background: We aimed to project the 10-year future incidence of cardiovascular disease (CVD) and model several intervention scenarios based on a multi-site Asian HIV-positive cohort., Methods: Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019-2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation., Results: Of 3,703 included patients, 69% were male, median age was 46 (IQR 40-53) years and median time since ART initiation was 9.8 years (IQR 7.5-14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL., Conclusions: Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.

Objective: Lower serum albumin (sAlb) has been associated with an increased risk of mortality and AIDS among people living with HIV and may be associated with the development of serious non-AIDS events (SNAEs). We evaluated the long-term association between sAlb and the risk of SNAEs., Design: Prospective multinational cohort study., Methods: D:A:D participants without SNAEs were followed from first routine sAlb value to the first of a new SNAE [cardiovascular disease (CVD), end-stage liver disease (ESLD), end-stage renal disease (ESRD), non-AIDS malignancy (NADM), death from non-AIDS cause], AIDS-death, 6 months after last visit or 1 February 2016. Poisson regression was used to determine associations between sAlb and a new SNAE, CVD, or NADM event, with adjustment for potential confounders. Models additionally tested whether the associations were modified by age, follow-up time, smoking status, CD4 and viral load., Results: Of 16 350 participants (71.8% male, median age 44 years), 1463 developed an SNAE (371 CVD, 200 ESLD, 40 ESRD, 553 NADM, 299 deaths from other non-AIDS causes) over 80 264 person-years. Increased sAlb was associated with a decreased risk of an SNAE [adjusted rate ratio per 5 g/l: SNAE 0.79 (95% confidence interval: 0.76, 0.83); CVD 0.87 (0.80, 0.94); NADM 0.88 (0.82, 0.95)]. The association did not appear to wane with additional years of follow-up (P-interaction = 0.79) but was stronger for current smokers than for never smokers (P-interaction <0.01)., Conclusion: sAlb is a durable risk factor for SNAE. Future studies are needed to determine the mechanism underlying this association and to evaluate the value of sAlb in predictive tools.

Background: Although earlier protease inhibitors have been associated with increased risk of cardiovascular disease, whether this increased risk also applies to more contemporary protease inhibitors is unknown. We aimed to assess whether cumulative use of ritonavir-boosted atazanavir and ritonavir-boosted darunavir were associated with increased incidence of cardiovascular disease in people living with HIV., Methods: The prospective Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study consists of people living with HIV-1 from 11 cohorts in Australia, Europe, and the USA. Participants were monitored from Jan 1, 2009, until the earliest of a cardiovascular event, 6 months after the last visit, or until Feb 1, 2016. The outcome of interest was the incidence of cardiovascular disease in adults (aged ≥16 years) living with HIV who were being treated with contemporary treatments. We defined cardiovascular disease as centrally validated myocardial infarction, stroke, sudden cardiac death, or use of invasive cardiovascular procedures, including coronary bypass, coronary angioplasty, and carotid endarterectomy. We used Poisson regression models to assess the associations between cardiovascular disease and the contempoary protease inhibitors atazanavir and darunavir (both boosted with ritonavir)., Findings: 49 709 participants were enrolled in the original cohort from 1999 onwards; 35 711 (71·8%) participants with available data on CD4 cell count and viral load at the 2009 baseline were included in the current analysis, and 13 998 (28·2%) participants had insufficent follow-up data after 2009. During a median 6·96 years of follow-up (IQR 6·28-7·08), 1157 people developed cardiovascular disease (incidence rate 5·34 events per 1000 person-years; 95% CI 5·03-5·65). The incidence rate of cardiovascular disease progressively increased from 4·91 events per 1000 person-years (4·59-5·23) in individuals unexposed to ritonavir-boosted darunavir to 13·67 events per 1000 person-years (8·51-18·82) in those exposed to the drug for more than 6 years. The changes associated with ritonavir-boosted atazanavir were less pronounced, showing an incidence rate of 5·03 cardiovascular events per 1000 person-years (4·69-5·37) in unexposed individuals to 6·68 events per 1000 person-years (5·02-8·35) in participants exposed for more than 6 years. After adjustment, keeping factors on the potential causal pathway from boosted protease inhibitor use to cardiovascular disease fixed at baseline, ritonavir-boosted darunavir use was associated with increased risk of cardiovascular disease (incidence rate ratio 1·59; 95% CI 1·33-1·91 per 5 years additional use), but use of ritonavir-boosted atazanavir was not (1·03; 0·90-1·18). This association remained after adjustment for time-updated factors on the potential causal pathway; myocardial infarction and stroke separately; plasma bilirubin concentration; and after stratification by use of ritonavir-boosted darunavir as the first ever protease inhibitor, used in combination with a non-nucleoside reverse transcriptase inhibitor, by previous virological failure, and by those at high risk of cardiovascular disease., Interpretation: Cumulative use of ritonavir-boosted darunavir, but not of ritonavir-boosted atazanavir, is associated with progressively increasing risk of cardiovascular disease. Causal inference is limited by the observational nature of the D:A:D study. Our findings should prompt investigation into the possible underlying mechanisms of this finding., Funding: The Highly Active Antiretroviral Therapy Oversight Committee., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study., Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders., Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25])., Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Cardiovascular disease (CVD) has a higher incidence in patients with HIV infection. This study sought to determine whether HIV-infected patients with established CVD were being managed according to national guidelines. Data were collected from Australian general practitioners for 77 HIV-infected patients with a median age of 59 (range 54-64). There was good adherence to guidelines with regards to anti-platelet (84%; n=65; 95% confidence interval (CI) 74-92%) and statin therapy (97%; n=75; 95% CI 91-100%), despite a failure to meet cholesterol targets, with only 31% (n=24; 95% CI 21-42%) of the cohort meeting low-density lipoprotein target values. Similarly, there was limited adherence to guidelines regarding the prescriptions of medications for those with established hypertension (66%; n=51; 95% CI 55-77%), body mass index targets met (40%; n=31; 95% CI 29-52%), and depression screening (32%; n=25; 95% CI 22-44%). This Australian audit provides insight into adherence to guidelines for individuals with CVD and HIV, suggesting that current screening and management practices for these patients falls short of guidelines, particularly in relation to cholesterol management.

Background: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has developed predictive risk scores for cardiovascular disease (CVD) and chronic kidney disease (CKD, defined as confirmed estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) events in HIV-positive people. We hypothesized that participants in D:A:D at high (>5%) predicted risk for both CVD and CKD would be at even greater risk for CVD and CKD events., Methods and Findings: We included all participants with complete risk factor (covariate) data, baseline eGFR > 60 ml/min/1.73 m2, and a confirmed (>3 months apart) eGFR < 60 ml/min/1.73 m2 thereafter to calculate CVD and CKD risk scores. We calculated CVD and CKD event rates by predicted 5-year CVD and CKD risk groups (≤1%, >1%-5%, >5%) and fitted Poisson models to assess whether CVD and CKD risk group effects were multiplicative. A total of 27,215 participants contributed 202,034 person-years of follow-up: 74% male, median (IQR) age 42 (36, 49) years, median (IQR) baseline year of follow-up 2005 (2004, 2008). D:A:D risk equations predicted 3,560 (13.1%) participants at high CVD risk, 4,996 (18.4%) participants at high CKD risk, and 1,585 (5.8%) participants at both high CKD and high CVD risk. CVD and CKD event rates by predicted risk group were multiplicative. Participants at high CVD risk had a 5.63-fold (95% CI 4.47, 7.09, p < 0.001) increase in CKD events compared to those at low risk; participants at high CKD risk had a 1.31-fold (95% CI 1.09, 1.56, p = 0.005) increase in CVD events compared to those at low risk. Participants' CVD and CKD risk groups had multiplicative predictive effects, with no evidence of an interaction (p = 0.329 and p = 0.291 for CKD and CVD, respectively). The main study limitation is the difference in the ascertainment of the clinically defined CVD endpoints and the laboratory-defined CKD endpoints., Conclusions: We found that people at high predicted risk for both CVD and CKD have substantially greater risks for both CVD and CKD events compared with those at low predicted risk for both outcomes, and compared to those at high predicted risk for only CVD or CKD events. This suggests that CVD and CKD risk in HIV-positive persons should be assessed together. The results further encourage clinicians to prioritise addressing modifiable risks for CVD and CKD in HIV-positive people.

Understanding the extent to which vascular disease and its risk factors are associated with prodromal dementia, notably Alzheimer's disease (AD), may enhance predictive accuracy as well as guide early interventions. One promising avenue to determine this relationship consists of looking for reliable and sensitive in-vivo imaging methods capable of characterizing the subtle brain alterations before the clinical manifestations. However, little is known from the imaging perspective about how risk factors such as vascular disease influence AD progression. Here, for the first time, we apply an innovative T1 and DTI fusion analysis of 3D corpus callosum (CC) on mild cognitive impairment (MCI) populations with different levels of vascular profile, aiming to de-couple the vascular factor in the prodromal AD stage. Our new fusion method successfully increases the detection power for differentiating MCI subjects with high from low vascular risk profiles, as well as from healthy controls. MCI subjects with high and low vascular risk profiles showed differed alteration patterns in the anterior CC, which may help to elucidate the inter-wired relationship between MCI and vascular risk factors.

Background: While the association between renal impairment and cardiovascular disease (CVD) is well established in the general population, the association remains poorly understood in human immunodeficiency virus (HIV)-positive individuals., Methods: Individuals with ≥2 estimated glomerular filtration rate (eGFR) measurements after 1 February 2004 were followed until CVD, death, last visit plus 6 months, or 1 February 2015. CVD was defined as the occurrence of centrally validated myocardial infarction, stroke, invasive cardiovascular procedures, or sudden cardiac death., Results: During a median follow-up duration of 8.0 years (interquartile range, 5.4-8.9 years) 1357 of 35 357 individuals developed CVD (incidence rate, 5.2 cases/1000 person-years [95% confidence interval {CI}, 5.0-5.5]). Confirmed baseline eGFR and CVD were closely related with 1.8% of individuals (95% CI, 1.6%-2.0%) with an eGFR > 90 mL/minute/1.73 m(2) estimated to develop CVD at 5 years, increasing to 21.1% (95% CI, 6.6%-35.6%) among those with an eGFR ≤ 30 mL/minute/1.73 m(2) The strong univariate relationship between low current eGFR and CVD was primarily explained by increasing age in adjusted analyses, although all eGFRs ≤ 80 mL/minute/1.73 m(2) remained associated with 30%-40% increased CVD rates, and particularly high CVD rates among individuals with an eGFR ≤ 30 mL/minute/1.73 m(2) (incidence rate ratio, 3.08 [95% CI, 2.04-4.65])., Conclusions: Among HIV-positive individuals in a large contemporary cohort, a strong relation between confirmed impaired eGFR and CVD was observed. This finding highlights the need for renal preventive measures and intensified monitoring for emerging CVD, particularly in older individuals with continuously low eGFRs., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objectives: The aim of the study was to assess the prevalence and characteristics associated with current smoking in an Asian HIV-positive cohort, to calculate the predictive risks of cardiovascular disease (CVD), coronary heart disease (CHD) and myocardial infarction (MI), and to identify the impact that simulated interventions may have., Methods: Logistic regression analysis was used to distinguish associated current smoking characteristics. Five-year predictive risks of CVD, CHD and MI and the impact of simulated interventions were calculated utilizing the Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) algorithm., Results: Smoking status data were collected from 4274 participants and 1496 of these had sufficient data for simulated intervention calculations. Current smoking prevalence in these two groups was similar (23.2% vs. 19.9%, respectively). Characteristics associated with current smoking included age > 50 years compared with 30-39 years [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.51-0.83], HIV exposure through injecting drug use compared with heterosexual exposure (OR 3.03; 95% CI 2.25-4.07), and receiving antiretroviral therapy (ART) at study sites in Singapore, South Korea, Malaysia, Japan and Vietnam in comparison to Thailand (all OR > 2). Women were less likely to smoke than men (OR 0.11; 95% CI 0.08-0.14). In simulated interventions, smoking cessation demonstrated the greatest impact in reducing CVD and CHD risk and closely approximated the impact of switching from abacavir to an alternate antiretroviral in the reduction of 5-year MI risk., Conclusions: Multiple interventions could reduce CVD, CHD and MI risk in Asian HIV-positive patients, with smoking cessation potentially being the most influential., (© 2016 British HIV Association.)

Objectives: The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes., Methods: We analysed data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after initiation (continuous variable) in treatment-naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI [weight (kg)/(height (m))(2)] was categorized as underweight (< 18.5), normal (18.5-25), overweight (25-30) and obese (> 30). Poisson regression models were fitted stratified for each pre-ART BMI category to allow for category-specific estimates of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4 count, key known risk factors (time-updated where possible) and calendar year., Results: A total of 97 CVD events occurred in 43,982 person-years (n = 9321) and 125 diabetes events in 43,278 person-years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37); normal, 1.18 (1.05-1.33); overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction > 0.05)., Conclusions: Short-term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre-ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre-ART BMI., (© 2015 British HIV Association.)

Background: With the aging of the population living with HIV, the absolute risk of cardiovascular disease (CVD) is increasing. There is a need to further facilitate the identification of persons at elevated risk in routine practice., Methods and Results: Prospective information was collected on 32,663 HIV-positive persons from 20 countries in Europe and Australia, who were free of CVD at entry into the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Cox regression models (full and reduced) were developed that predict the risk of a global CVD endpoint. The predictive performance of the D:A:D models were compared with a recent CVD prediction model from the Framingham study, which was assessed recalibrated to the D:A:D dataset. A total of 1010 CVD events occurred during 186,364.5 person-years. The full D:A:D CVD prediction model included age, gender, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, high-density lipoprotein, CD4 lymphocyte count, cumulative exposure to protease- and nucleoside reverse transcriptase-inhibitors, and current use of abacavir. A reduced model omitted antiretroviral therapies. The D:A:D models statistically significantly predicted risk more accurately than the recalibrated Framingham model (Harrell's c-statistic of 0.791, 0.783 and 0.766 for the D:A:D full, D:A:D reduced, and Framingham models respectively; p < 0.001). The D:A:D models also more accurately predicted five-year CVD-risk for key prognostic subgroups., Conclusions: An updated, easily recalibrated, global CVD-risk equation tailored to HIV-positive persons was developed using routinely collected CVD risk parameters and incorporating markers on immune function (CD4 lymphocyte count), and exposure to antiretroviral therapies. The estimated CVD risk can be used to quantify risk and to guide preventive care., (© The European Society of Cardiology 2015.)

Objective: To consider associations between the latest/nadir CD4 cell count, and time spent with CD4 cell count less than 200 cells/μl (duration of immune depression), and myocardial infarction (MI), coronary heart disease (CHD), stroke, or cardiovascular disease (CVD) (CHD or stroke) in 33 301 HIV-positive individuals., Design: Longitudinal cohort study., Methods: Analyses were undertaken using Poisson regression. To investigate whether analyses of stroke were robust to the type of endpoint, we additionally included stroke-like events and rejected strokes into the stroke endpoint., Results: Participants experienced 716 MI, 1056 CHD, 303 stroke, and 1284 CVD events. Whereas there was no evidence of a higher MI/CHD risk in those with lower latest/nadir CD4 cell counts after adjustment [current CD4 <100 cells/μl: relative rate (95% confidence interval) 0.96 (0.62-1.50) for MI, 0.89 (0.30-2.36) for CHD; nadir CD4 <100 cells/μl: 1.36 (0.57-3.23) for MI, 0.98 (0.45-2.16) for CHD], stroke and CVD rates were higher in those with a latest CD4 cell count less than 100 cells/μl [2.26 (1.29-3.94) and 1.14 (0.84-1.56), respectively]. All events occurred less frequently in those who had not experienced immune depression, although evidence for a linear association with duration of immune depression was weak. The association between stroke risk and the latest CD4 cell count strengthened as stroke-like and rejected strokes were included; conversely, associations with established stroke risk factors weakened., Conclusion: We do not find strong evidence that HIV-positive individuals with a low CD4 cell count are more likely to experience MI/CHD. Although strokes appear to occur more commonly at low CD4 cell counts, this may be partly explained by misclassification or other biases.

Objective: To estimate the overall and cause specific mortality of Aboriginal offenders in New South Wales (NSW), Australia., Methods: The study cohort consisted of all Aboriginal men and women aged 18 years and older who had experienced full-time imprisonment in NSW between 1 January 1988 and 31 December 2002. Their data were linked probabilistically to the Australian National Death Index to obtain information on death. Standardised mortality ratios were calculated for all causes of death and adjusted for age, sex, and calendar year., Results: The cohort comprised 7,980 men and 1,373 women with 75,801 person years of observation. During a median follow-up period of 8.3 years, 485 men and 73 women died, giving an overall mortality rate of 733 and 755 deaths per 100,000 person-years. The risk of death in men was 4.8 (95% CI: 4.4-5.3) times and among women 12.6 (95% CI: 10.0-15.8) times that of the NSW residents, with a markedly elevated risk for almost all conditions. The leading cause of death was cardiovascular disease in men (112 deaths, 23%) and mental and behavioural disorders (17 deaths, 23%) in women. The risk of death was greatest following release from prison., Conclusions and Implications: High mortality rates for cardiovascular disease, a preventable and treatable condition, were seen among Aboriginal offenders. Prison has an important role to play in screening marginalised populations for a range of health conditions. This is particularly true for Indigenous offenders., (© 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.)

Dividing people into 'hypertensives' and 'normotensives' is commonplace but problematic. The relationship between blood pressure and cardiovascular disease is continuous. The Prospective Studies Collaboration analysis shows a continuous straight line dose-response relationship across the entire population down to blood pressure levels of 115 mmHg systolic and 75 mmHg diastolic, the confidence limits on the individual data points being sufficiently narrow to exclude even a minor deviation from a linear relationship. Meta-analysis of randomized controlled trials shows that blood pressure-lowering drugs produce similar proportional reductions in risk of coronary heart disease (CHD) and stroke irrespective of pre-treatment blood pressure, down to levels of 110 mmHg systolic and 70 mmHg diastolic. There are also now sufficient trial data to show a statistically significant risk reduction in 'normotensive' people without known vascular disease on entry. The straight line (log-linear) relationship means that the benefit derived from lowering blood pressure is proportional to existing risk, so the decision on whom to treat with blood pressure-lowering drugs should depend on a person's overall absolute risk irrespective of blood pressure. In primary prevention, basing treatment on age alone rather than overall absolute risk entails little loss of efficacy and may be preferred on the basis of simplicity and avoidance of anxiety in telling people they are at elevated risk.

Objectives: The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection., Methods: Patients who reported smoking status and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all-cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment., Results: A total of 27 136 patients had smoking status reported, with totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after >3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all-cause mortality., Conclusion: The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV-positive patients., (© 2011 British HIV Association.)

Objective: To investigate any emerging trends in causes of death amongst HIV-positive individuals in the current cART era, and to investigate the factors associated with each specific cause of death., Design: An observational multicentre cohort study., Methods: All HIV-positive individuals included in one of the cohorts in the Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study were included. The association between HIV-specific and non HIV-specific risk factors and death were studied using multivariable Poisson regression., Results: We observed 2482 deaths in 180,176 person-years (PY) on 33,308 individuals [rate/1000 PY = 13.8 (95% CI 13.2-14.3)]. Primary causes of death were: AIDS (n = 743; rate/1000 PY = 4.12), liver-related (341; 1.89), CVD-related (289; 1.60), non-AIDS malignancy (286; 1.59). The overall rate of death fell from 16.9 in 1999/2000 to 9.6/ 1000 PY in 2007/2008. Smoking was associated with CVD and non-AIDS cancers, HBV and HCV co-infection with liver-related deaths, and hypertension with liver-related and CVD deaths. Diabetes was a risk factor for all specific causes of death except non-AIDS cancers, and higher current HIV RNA for AIDS-related deaths. Lower CD4 cell counts were associated with a higher risk of death from all specific causes of death., Conclusion: Multiple potentially modifiable traditional and HIV-specific risk factors for death of HIV-infected persons were identified. The maximum reduction in mortality in HIV-infected populations will require that each of these factors be appropriately addressed. No trends in terms of emerging causes of unexpected deaths were observed, although monitoring will continue.

Objective: It is much debated whether the metabolic syndrome contributes additional information over and above that provided by the individual components of the syndrome alone. Among HIV-infected individuals, we investigated whether any particular combinations of the components included in the definition of the metabolic syndrome are associated with a higher risk of cardiovascular disease (CVD)., Research Design and Methods: We followed 33,347 HIV-infected individuals in a prospective observational study. The effect of combinations of components of the metabolic syndrome (low HDL cholesterol, high triglycerides, high BMI, hypertension, and diabetes) on the risk of CVD was assessed by Poisson regression incorporating interactions between each component pair and adjusting for age, sex, family history of CVD, smoking status, calendar year, and exposure to antiretroviral therapy. We reduced the risk of type 1 errors by randomly splitting the data set for training (70% of sample) and validation (remaining 30%)., Results: In the training data set, 671 patients experienced a CVD event over 110,652 person-years. Unadjusted, the presence of metabolic syndrome at study enrollment (>or=3 of the factors) was associated with a 2.89 higher risk of CVD (95% CI 2.34-3.59; P = 0.0001) compared with individuals without the metabolic syndrome. After adjustment for the individual components, the metabolic syndrome as an entity no longer predicted the risk of CVD (adjusted relative risk 0.85; 95% CI 0.61-1.17; P = 0.32). No significant positive interactions were found among the components of the metabolic syndrome., Conclusions: The presence of the metabolic syndrome in HIV-infected individuals did not appear to increase the CVD risk over and above that conferred by the components of the syndrome separately.

Molecular cardiovascular imaging plays an increasingly important role both in basic research and in clinical diagnosis. Scintigraphic methods have long been used to study pathophysiological changes on a cellular and molecular level, and they are likely to remain important molecular imaging modalities in the foreseeable future. This article provides an overview over current developments in cardiovascular molecular imaging using scintigraphic methods. The focus lies on imaging of cardiac innervation, plaque instability, hypoxia and angiogenesis, gene expression and stem and progenitor cell migration and proliferation.

This paper summarises the main evidence and conclusions relating to using blood pressure measurement as a screening test to identify people who will develop ischaemic heart disease (IHD) or stroke, as recently published in a Health Technology Assessment report. While blood pressure is recognised as an important cause of stroke and IHD, and lowering blood pressure can substantially lower the risk of these diseases, the measurement of blood pressure is a poor screening test. It is not good in distinguishing those who will and will not develop these diseases. The poor screening performance is illustrated by the findings that in the largest cohort study, persons in the top 10% of the distribution of systolic blood pressure experienced only 21% of all IHD events and 28% of all strokes at a given age. Using several cardiovascular risk factors in combination does not add materially to the poor screening performance of blood pressure alone. Among persons in a specified age group, the 5% at highest risk experience 17% of all heart disease deaths with risk computation based on blood pressure alone, 22% when based on blood pressure and apolipoprotein B (or LDL cholesterol) in combination, and only 28% using these two, smoking and three other cardiovascular risk factors all in combination. Identifying patients at the time of hospital discharge following myocardial infarction or stroke is the most effective screening test to identify those who will die of cardiovascular disease. In patients with a history of myocardial infarction or stroke the cardiovascular death rate in the absence of treatment is about 5% per year, a risk that persists for at least 15 years. In the absence of treatment, about half of all deaths from heart disease in a population occur after hospital discharge following the first infarct. Among persons with no history of cardiovascular disease, age is a better screening test than the reversible risk factors, and the best policy is to offer treatment to all persons above a specified age such as 55 years.

Objective: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies., Design: Baseline data from 17,852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999., Methods: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy., Results: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (> or = 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (CI), 1.45-2.22], PI but no NNRTI (OR, 2.35; 95% CI, 1.92-2.87), or NNRTI + PI (OR, 5.48; 95% CI, 4.34-6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level., Conclusion: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.

Reducing dietary saturated fat by 7% of energy, a realistic target, would reduce serum cholesterol by 10% and mortality from ischemic heart disease by 25-30%. Randomized trials show that this mortality reduction is attained rapidly, usually by the third year after initial reduction of dietary saturated fat intake. Dietary change in adulthood may therefore reverse the adverse health effects of a high-fat diet in childhood. In the absence of such change, however, dietary fat in childhood may increase the risk of cardiovascular disease in adult life because of a longer duration of exposure to a high-fat diet. Assessing the effects of diet on cancer risk is more difficult. The intermediary markers of risk that are analogous to serum cholesterol are less satisfactory and there are negligible trial data. Cohort studies of diet and cancer, although subject to bias, do not favor a direct causal relation between dietary fat and cancer. But a reduction in risk is likely when dietary fat is reduced as part of a general change toward a healthier diet. The trend toward increased energy intake and body size in childhood and relatively low dietary fiber contribute to the decreasing age at menarche, which is associated with an increased risk of breast cancer. Low dietary fiber, low fruit and vegetable consumption, and high red meat consumption are associated with colon cancer and other cancers, and important causal effects of diet on cancer are likely. As with cardiovascular disease, this dietary trend that is commenced in childhood is likely to increase age-specific rates of colon cancer in adult life, but the risk may be reversed with later dietary change.

The rise in average blood pressure with age seen in Western populations does not occur in isolated traditional nomadic communities. Several factors contribute to the higher blood pressure in the West. Salt is particularly important, however, because its effect on blood pressure is large, the dietary intake by Western populations is high and a large reduction in its intake is realistic. The size of the relationship between salt and blood pressure depends on age and, in trials, the duration of reduction of intake of salt. Results of many of the randomized trials have suggested that reduction of dietary salt exerts only a small effect on average blood pressure; this is because their subjects have been young (average age 26 years) and trials have been of short duration (average 2 weeks). Analysis of observational data concerning various communities indicated that a reduction in dietary intake of sodium of 100 mmol/24 h (3 g of salt, a realistic reduction) lowers systolic blood pressure in subjects aged 50-65 years by 10 mmHg on average. Much evidence corroborates this estimate, including data from the Intersalt study and a randomized controlled trial of reduction of intake of salt by older persons. This reduction in blood pressure would reduce age-specific stroke mortality by an estimated 22% and mortality from heart disease by 16%. Reducing the amount of salt added to manufactured foods is an important public-health target.

In the British United Provident Association (BUPA) study, a prospective observational study of 21,520 men, the serum albumin of 877 men who died during 10 years of follow-up was compared with that of 877 controls, each matched to a case by age (within 1 year) and date of attendance (within 3 months). There was little overall difference (mean case-control difference = -0.11 milligram, P > 0.2) despite the fact that other studies have reported a long-term association between low serum albumin and increased mortality. Cause-specific mortality data showed no association of low albumin with ischaemic heart disease or other circulatory diseases. An inverse association with cancer was confined to the first few years of follow-up and so attributable to pre-clinical cancer lowering both serum albumin itself and serum cholesterol, with which albumin was associated. There was an association of chronic respiratory, neurological, renal, liver and gut diseases with low serum albumin (case-control difference = -1.19 milligram, P < 0.001) consistent with the effect of pre-clinical disease lowering serum albumin. Other causes of death showed no association with albumin. Our data do not support a cause and effect association of low serum albumin and mortality. [ABSTRACT FROM AUTHOR]

Accumulating evidence supports an effect of aspirin in reducing cancer incidence and mortality. Our analyses show that prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use.Background Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. Methods The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. Results The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. Conclusions Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening–eradication before starting aspirin prophylaxis. [ABSTRACT FROM PUBLISHER]