Changes in Glomerular Filtration Rate After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Fumarate for Human Immunodeficiency Virus Preexposure Prophylaxis.

Background: Tenofovir alafenamide fumarate (TAF) was promoted as a safer alternative to tenofovir disoproxil fumarate (TDF) for human immunodeficiency virus oral preexposure prophylaxis (PrEP). It is unknown if switching from TDF to TAF translates to improved renal function. We used electronic health record (EHR) data to assess changes in creatinine-estimated glomerular filtration rate (eGFR) after switching from TDF to TAF. Methods: We conducted a retrospective cohort study using EHR data from Kaiser Permanente Southern California. We identified individuals who switched from TDF to TAF between October 2019 and May 2022 and used time-varying propensity score matching to identify controls who were on TDF ("nonswitchers"). We then used Bayesian longitudinal modeling to compare differences in eGFR between switching and nonswitching scenarios. Results: Among 5246 eligible individuals, we included 118 TDF to TAF switchers and 114 nonswitchers. Compared to nonswitchers, switchers had older age of starting TDF but similar body weights at index date. A higher proportion of switchers were White, on Medicare or Medicaid, and had dyslipidemia at index date. Switching to TAF was associated with a higher eGFR compared to staying on TDF in 3-15 months post-switch, but the differences were not statistically significant (eg, month 9 difference: 1.27 [95% credible interval, -1.35 to 3.89]). While most of the estimated changes showed eGFR increase associated with switching, most were <2 eGFR units. Sensitivity analyses to address missingness or nonadherence showed similar results. Conclusions: Switching from TDF to TAF for PrEP was associated with a nonsignificant increase in eGFR. Findings need to be confirmed using larger cohorts.

Renal outcomes in adults with HBV, HIV and HBV/HIV coinfection after 3 years of antiviral therapy in urban Tanzania.

BACKGROUND: An enhanced understanding of renal outcomes in persons with chronic HBV, HIV, and HBV/HIV coinfection is needed to mitigate chronic kidney disease in regions where HBV and HIV are endemic. OBJECTIVES: To investigate changes in estimated glomerular filtration rate (eGFR) in adults with HBV, HIV or HBV/HIV enrolled in a 3 year prospective cohort study of liver outcomes in Dar es Salaam, Tanzania and initiated on antiviral therapy. METHODS: We compared eGFR between and within groups over time using mixed-effects models. RESULTS: Four hundred and ninety-nine participants were included in the analysis (HBV: 164; HIV: 271; HBV/HIV: 64). Mean baseline eGFRs were 106.88, 106.03 and 107.18 mL/min/1.73 m2, respectively. From baseline to Year 3, mean eGFR declined by 4.3 mL/min/1.73 m2 (95% CI -9.3 to 0.7) and 3.7 (-7.8 to 0.5) in participants with HBV and HIV, respectively, and increased by 5.1 (-4.7 to 14.9) in those with HBV/HIV. In multivariable models, participants with HBV had lower eGFRs compared with those with HIV or HBV/HIV and, after adjusting for HBV DNA level and hepatitis B e antigen (HBeAg) status, significantly lower eGFRs than those with HBV/HIV at all follow-up visits. CONCLUSIONS: In this Tanzanian cohort, coinfection with HBV/HIV did not appear to exacerbate renal dysfunction compared with those with either infection alone. Although overall changes in eGFR were small, persons with HBV experienced lower eGFRs throughout follow-up despite their younger age and similar baseline values. Longer-term studies are needed to evaluate continuing changes in eGFR and contributions from infection duration and other comorbidities.

Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems.

BACKGROUND: Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. SETTING: Retrospective analyses of electronic health record data from 3 US integrated health care systems. METHODS: Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. RESULTS: Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). CONCLUSIONS: Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.

Incident Kaposi sarcoma during the expansion of antiretroviral therapy eligibility in Nigeria: a retrospective cohort study.

INTRODUCTION: The expansion of antiretroviral therapy (ART) eligibility could lead to earlier initiation of Human Immunodeficiency Virus (HIV) treatment and consequently reduce the risk of HIV-associated Kaposi Sarcoma (KS). We investigated the impact of changes in the Nigerian HIV treatment guidelines on KS incidence among adults enrolled in HIV care in Nigeria. METHODS: We analyzed data of adults who enrolled for HIV care from January 2006 to December 2016 at one of Nigeria's largest HIV treatment centers. Based on changes in HIV treatment guidelines, we classified 2006-2009 as the pre-expansion period and 2010-2016 as the post-expansion period. We used Kaplan Meier curves to compare the incidence of KS in the pre-expansion to the post-expansion period. We used Cox regression models to assess the hazard for incident KS between the two periods after adjusting for potential confounders. RESULTS: Among 14,479 patients with HIV, the overall KS incidence was 2.35; 95% CI 2.01-2.74/1,000 person-years. The incidence of KS decreased from 2.53 to 1.58 per 1,000 person-years from 2006 to 2009 to 2010-2016. In models adjusting for age, sex, CD4-T cell count, and ART use, the risk for KS remained lower in 2010-2016 compared to 2006-2009. In analyses restricted to time on ART, there was no significant difference in KS incidence between HIV patients who enrolled in 2006-2009 and 2010-2016 after adjusting for age, sex, and CD4 T-cell count. CONCLUSION: The expansion of ART eligibility was associated with a reduced incidence of HIV-associated KS among adults initiating HIV care in Jos, Nigeria. The reduction was likely driven by earlier enrollment for HIV care and ART initiation.

Use of Tenofovir Alafenamide Fumarate for HIV Pre-Exposure Prophylaxis and Incidence of Hypertension and Initiation of Statins.

Importance: Pre-exposure prophylaxis (PrEP) is an important tool for preventing HIV infection. However, PrEP's impact on cardiometabolic health is understudied. Objective: To examine the risk of incident hypertension and statin initiation among adult (age ≥18 years) health plan members starting PrEP with tenofovir alafenamide fumarate (TAF) compared with propensity score-matched adults taking tenofovir disoproxil fumarate (TDF). Design, Setting, and Participants: This retrospective cohort study used electronic health records (EHRs) from Kaiser Permanente Southern California. Adult members starting PrEP in Kaiser Permanente Southern California between October 2019 and May 2022 were included. Propensity score matching with multiple imputation (50 matched data sets) was conducted to generate 1 TAF:4 TDF matched data sets with balanced baseline covariates. Exposures: PrEP initiation with either TAF or TDF during the study period. Main Outcomes and Measures: Incident hypertension and statin initiation within 2 years of PrEP initiation were ascertained through blood pressure and outpatient pharmacy records, respectively. Risk differences and odds ratios (ORs) were estimated using logistic regression and g-computation. Results: A total of 6824 eligible individuals were identified (mean [SD] age, 33.9 [10.3] years; 6618 [97%] male). This pool was used to generate 2 cohorts without baseline hypertension or statin use for matching (hypertension: n = 5523; statin: n = 6149) In both cohorts, those starting PrEP with TAF were older and were more likely to be non-Hispanic White compared with those starting with TDF. In matched analysis adjusting for baseline covariates, TAF use was associated with elevated risk of incident hypertension (TAF: n = 371; risk difference, 0.81 [95% CI, 0.12-1.50]; OR, 1.64 [95% CI, 1.05-2.56]). TAF use was also associated with elevated risk of statin initiation (TAF: n = 382; risk difference, 0.85 [95% CI, 0.37-1.33]; OR, 2.33 [95% CI, 1.41-3.85]). Subgroup analyses restricted to individuals 40 years and older at PrEP initiation showed similar results with larger risk difference in statin initiation (risk difference, 4.24 [95% CI, 1.82-6.26]; OR, 3.05 [95% CI, 1.64-5.67]). Conclusions and Relevance: In this study of people taking PrEP, TAF use was found to be associated with higher incident hypertension and statin initiation compared with TDF use, especially in those 40 years or older. Continued monitoring of blood pressure and lipids for TAF users is warranted.

Intersectionality-informed analysis of durable viral suppression disparities in people with HIV.

OBJECTIVE: The aim of this study was to examine drivers of durable viral suppression (DVS) disparities among people with HIV (PWH) using quantitative intersectional approaches. DESIGN: A retrospective cohort analysis from electronic health records informed by intersectionality to better capture the concept of interlocking and interacting systems of oppression. METHODS: We analyzed data of PWH seen at a LGBTQ federally qualified health center in Chicago (2012-2019) with at least three viral loads. We identified PWH who achieved DVS using latent trajectory analysis and examined disparities using three intersectional approaches: Adding interactions, latent class analysis (LCA), and qualitative comparative analysis (QCA). Findings were compared with main effects only regression. RESULTS: Among 5967 PWH, 90% showed viral trajectories consistent with DVS. Main effects regression showed that substance use [odds ratio (OR) 0.56, 0.46-0.68] and socioeconomic status like being unhoused (OR: 0.39, 0.29-0.53), but not sexual orientation or gender identity (SOGI) were associated with DVS. Adding interactions, we found that race and ethnicity modified the association between insurance and DVS ( P for interaction <0.05). With LCA, we uncovered four social position categories influenced by SOGI with varying rates of DVS. For example, the transgender women-majority class had worse DVS rates versus the class of mostly nonpoor white cisgender gay men (82 vs. 95%). QCA showed that combinations, rather than single factors alone, were important for achieving DVS. Combinations vary with marginalized populations (e.g. black gay/lesbian transgender women) having distinct sufficient combinations compared with historically privileged groups (e.g. white cisgender gay men). CONCLUSION: Social factors likely interact to produce DVS disparities. Intersectionality-informed analysis uncover nuance that can inform solutions.

Association of statin use with outcomes of patients admitted with COVID-19: an analysis of electronic health records using superlearner.

IMPORTANCE: Statin use prior to hospitalization for Coronavirus Disease 2019 (COVID-19) is hypothesized to improve inpatient outcomes including mortality, but prior findings from large observational studies have been inconsistent, due in part to confounding. Recent advances in statistics, including incorporation of machine learning techniques into augmented inverse probability weighting with targeted maximum likelihood estimation, address baseline covariate imbalance while maximizing statistical efficiency. OBJECTIVE: To estimate the association of antecedent statin use with progression to severe inpatient outcomes among patients admitted for COVD-19. DESIGN, SETTING AND PARTICIPANTS: We retrospectively analyzed electronic health records (EHR) from individuals ≥ 40-years-old who were admitted between March 2020 and September 2022 for ≥ 24 h and tested positive for SARS-CoV-2 infection in the 30 days before to 7 days after admission. EXPOSURE: Antecedent statin use-statin prescription ≥ 30 days prior to COVID-19 admission. MAIN OUTCOME: Composite end point of in-hospital death, intubation, and intensive care unit (ICU) admission. RESULTS: Of 15,524 eligible COVID-19 patients, 4412 (20%) were antecedent statin users. Compared with non-users, statin users were older (72.9 (SD: 12.6) versus 65.6 (SD: 14.5) years) and more likely to be male (54% vs. 51%), White (76% vs. 71%), and have ≥ 1 medical comorbidity (99% vs. 86%). Unadjusted analysis demonstrated that a lower proportion of antecedent users experienced the composite outcome (14.8% vs 19.3%), ICU admission (13.9% vs 18.3%), intubation (5.1% vs 8.3%) and inpatient deaths (4.4% vs 5.2%) compared with non-users. Risk differences adjusted for labs and demographics were estimated using augmented inverse probability weighting with targeted maximum likelihood estimation using Super Learner. Statin users still had lower rates of the composite outcome (adjusted risk difference: - 3.4%; 95% CI: - 4.6% to - 2.1%), ICU admissions (- 3.3%; - 4.5% to - 2.1%), and intubation (- 1.9%; - 2.8% to - 1.0%) but comparable inpatient deaths (0.6%; - 1.3% to 0.1%). CONCLUSIONS AND RELEVANCE: After controlling for confounding using doubly robust methods, antecedent statin use was associated with minimally lower risk of severe COVID-19-related outcomes, ICU admission and intubation, however, we were not able to corroborate a statin-associated mortality benefit.

Association of Cumulative Viral Load With the Incidence of Hypertension and Diabetes in People With HIV.

BACKGROUND: HIV induces several metabolic derangements that contribute to cardiovascular disease, but it is unclear if HIV increases diabetes or hypertension risk. Refining longitudinal relationships between HIV-specific factors and cardiovascular disease risk factors across different care settings may help inform cardiovascular disease prevention among people with HIV (PWH). METHODS: We tested the hypothesis that long-term higher cumulative viral load (viremia-copy-year) is associated with higher risk of diabetes and hypertension by analyzing electronic records of PWH from 2 distinct health systems in Chicago (Northwestern Medicine and Howard Brown Health Care) receiving care in 2004 to 2019. We used joint longitudinal-survival models to assess multivariable-adjusted associations. Subgroup analyses per site were also conducted. RESULTS: We observed 230 (3.0%) incident diabetes cases in 7628 PWH without baseline diabetes and 496 (6.7%) hypertension cases in 7450 PWH without baseline hypertension. Pooled analysis showed a direct association of viremia-copy-year with incident hypertension (hazards ratio, 1.20 [95% CI, 1.14-1.26]) but not with diabetes (hazards ratio, 1.03 [95% CI, 0.96-1.10]). However, site-specific differences existed whereby the Northwestern-only analysis demonstrated a significant association of viremia-copy-year with hypertension (hazards ratio, 1.29 [95% CI, 1.08-1.32]). Additionally, higher social deprivation index (both sites) and diagnosis of mental health disorder (Howard Brown Health only) was associated with higher diabetes and hypertension risk. CONCLUSIONS: Cumulative viral load may be associated with incident hypertension among PWH. Associations of HIV control with cardiovascular disease risk factors among PWH may differ by health care system context.

Ideal Cardiovascular Health: Distribution, Determinants and Relationship with Health Status among People Living with HIV in Urban Tanzania.

Background: Ageing adults living with HIV (ALHIV) have increased risk of cardiovascular diseases as a result of HIV-infection-related chronic immune activation and inflammatory responses. Cardiovascular health index (CVHI) is a valid and relatively simple index for assessing the cardiovascular health (CVH) of the general population. Use of this index among ALHIV in Sub Saharan Africa, a resource-restricted setting where it could be mostly beneficial, remains limited. Understanding of the distribution and associated factors may inform the design of optimal interventions to improve CVH of ALHIV. Objective: We aimed to assess the distribution and factors associated with CVHI scores among ALHIV in an urban setting in Tanzania. Methods: A cross-sectional study was conducted among ALHIV on antiretroviral therapy at six HIV clinics in Dar-es-Salaam, Tanzania. We summed the score of each of the seven CVHI metric to obtain the overall CVHI score and assessed the distribution of the score by sex. We then categorized the overall score into ideal (5-7), intermediate (3-4) and poor (<3) CVH categories and performed ordinal regression to identify CVHI score associated factors. Results: In all, 629 ALHIV [mean age of 43.5(SD ± 11.2) years] were enrolled. Most had ideal levels of blood glucose (96.2%) and smoking status (83.4%) while less than half had ideal BMI (48.1%), blood pressure (BP) (43.9%) and dietary intake (7.8%). Less than half (47.6%) showed ideal CVH, while less than 1% had all seven metrics at ideal level. Older age (0.96(95%CI:0.95-0.97), p-value < 0.001), being retired/unemployed (0.59(95%CI:0.43-0.81), p-value < 0.01), being employed (0.76(95%CI:0.62-0.94), p-value = 0.01) alcohol use (0.41(95%CI:0.21-0.80), p-value = 0.01) and presence of non-communicable disease comorbidities (0.68(95%CI:0.48-0.97), p-value = 0.04) had significant lower odds of ideal CVH. Conclusion: Based on our findings, interventions to improve CVH of ALHIV should target BP management, health education on diet for BMI control and reduction in alcohol consumption, particularly among ageing ALHIV with comorbidities.

Estimating the EQ-5D-5L value set for the Philippines.

BACKGROUND: The Philippines has recommended the use of Quality-Adjusted Life Years (QALYs) in government health technology assessments (HTA). We aimed to develop a value set for the EQ-5D-5L based on health preferences of the healthy general adult population in the Philippines. METHODS: Healthy, literate adults were recruited from the Philippine general population with quota targets based on age, sex, administrative region, type of residence, education, income, and ethnolinguistic groups. Each participant's preference was elicited by completing Composite Time Trade-Off (C-TTO) and Discrete Choice Experiment (DCE) tasks. Tasks were computer-assisted using the EuroQol Valuation Technology 2.0. To estimate the value set, we explored 20- and 8-parameter models that either use c-TTO-only data or both c-TTO and DCE (also called hybrid models). Final model choice was guided by principles of monotonicity, out-of-sample likelihood, model fit, and parsimony. RESULTS: We recruited 1000 respondents with demographic characteristics that approximate the general population such as 49.6% Female, 82% Roman Catholic, 40% in urban areas, and 55% finished high school. None of the 20-parameter models demonstrated monotonicity (logical worsening of coefficients with increasing severity). From the 8-parameter models, the homoscedastic TTO-only model exhibited the best fit. From this model, mobility and pain/ discomfort had the highest effect on utilities. CONCLUSION: The selected model for representing the Philippine general population preferences for EQ-5D-5L health states was an 8-parameter homoscedastic TTO-only model. This value set is recommended for use in QALY calculations in support of HTA-informed coverage decisions in the Philippines.

Phenotypic Presentations of Heart Failure Among Patients With Chronic Inflammatory Diseases.

Objective: Characterize incident heart failure (HF) phenotypes among patients with various chronic inflammatory diseases (CIDs). Background: Several CIDs are associated with increased HF risk, but differences in HF phenotypes across CIDs are incompletely understood. No prior studies to our knowledge have manually adjudicated HF phenotypes across a CID spectrum. Methods: We screened for patients with-and controls without-CIDs who had possible HF, then hand-adjudicated HF endpoints. Possible HF resulted from a single HF administrative code; HF was deemed definite/probable vs. absent using standardized, validated criteria. We queried adjudicated HF patients' charts to define specific HF phenotypes, then compared clinical, demographic, and HF phenotypic characteristics for HF patients with specific CIDs vs. non-CID controls using Fisher's exact test. Results: Out of 415 possible HF patients, 192 had definite/probable HF. Significant differences in HF phenotypes existed across CIDs. Isolated right-sided HF was present in 27.8% of patients with SSc and adjudicated HF, which is more than twice as common as it was in any other CID. Left ventricular systolic dysfunction was most common in patients with HIV and lupus (SLE); mean LVEF was 45.0% ± 18.6% for HIV and 41.3% ± 17.1% for SLE, but was 57.7% ± 10.7% for SSc. Those with HIV and multiple CIDs were most likely to have coronary artery disease. Conclusions: Different CIDs present with different phenotypes of physician-adjudicated HF, potentially reflecting different underlying inflammatory pathophysiologies. Larger studies are needed to confirm these findings, as are mechanistic studies focused on understanding specific immunoregulatory contributors to HF.

Analyses of Kaposi Sarcoma trends among adults establishing initial outpatient HIV care in Nigeria: 2006-2017.

BACKGROUND: The incidence of Human Immunodeficiency Virus (HIV)-associated Kaposi Sarcoma (KS) in the pre-antiretroviral therapy (ART) population remains high in several countries in sub-Saharan Africa. We examined trends of KS prevalence in adults, establishing initial outpatient HIV care from 2006 to 2017 in Nigeria. METHODS: We analyzed data of 16,431 adults (age ≥ 18 years) enrolled for HIV care from January 1, 2006, to December 31, 2017, in a large clinic in Jos, Nigeria. KS at enrollment was defined as KS recorded in the electronic health record within 30 days of clinic enrollment. Time trends were compared among four periods: 2006-2008, 2009-2011, 2012-2014, and 2015-2017 using logistic regression models. Annual trends were analyzed using join point regression and restricted splines. RESULTS: The study population had a mean age 35.1 (standard deviation, SD 9.5) years, and were 65.7% female (n = 10,788). The mean CD4 cell count was 220 (95% CI 117-223). The overall KS prevalence at entry was 0.59% (95% CI 0.48-0.72). Compared to 2006-2008, KS prevalence was significantly higher in 2009-2011 (adjusted odds ratio 5.07 (95% CI 3.12-8.24), p < 0.001), but remained unchanged in subsequent periods. Male sex and low CD4 T-cell count independently increased odds for KS. CONCLUSIONS: Despite ART expansion, KS at enrollment showed no significant decline. The low CD4 cell count, across all periods, indicates delay in enrollment for HIV care, which increases KS risk. Interventions aimed at early HIV diagnosis and linkage to ART is critical to KS risk reduction in this population.

Assessing widening disparities in HbA1c and systolic blood pressure retesting during the COVID-19 pandemic in an LGBTQ+-focused federally qualified health center in Chicago: a retrospective cohort study using electronic health records.

INTRODUCTION: To assess disparities in retesting for glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) among people with diabetes mellitus (DM) and hypertension (HTN), respectively, we analyzed medical records from a lesbian, gay, bisexual, transgender, queer-specialized federally qualified health center with multiple sites in Chicago. RESEARCH DESIGN AND METHODS: We identified people with DM seen in 2018 and 2019 then assessed if individuals had HbA1c retested the following year (2019 and 2020). We repeated this using SBP for people with HTN. Rates of retesting were compared across gender, sexual orientation, and race and ethnicity and across the 2 years for each categorization with adjustment for socioeconomic indicators. RESULTS: Retesting rates declined from 2019 to 2020 for both HbA1c and SBP overall and across all groups. Cisgender women and transgender men with DM (vs cisgender men) and straight people (vs gay men) had significantly lower odds of HbA1c retesting for both years. There was evidence of widening of HbA1c retesting disparities in 2020 between gay men and other orientations. Cisgender women, straight people, and black people (vs white) with HTN had significantly lower odds of SBP retesting for both years. There was evidence of narrowing in the retesting gap between black and white people with HTN, but this was due to disproportionate increase in no retesting in white people rather than a decline in no retesting among black people with HTN. CONCLUSIONS: Disparities in DM and HTN care according to gender, race, ethnicity, and sexual orientation persisted during the pandemic with significant widening according to sexual orientation.

Changes in proportionate cardiovascular mortality in patients with chronic infectious and inflammatory conditions in the United States, 1999-2018.

Treatment options for several chronic infectious and inflammatory conditions have expanded in recent years. This may have implications for evolving competing risks for chronic inflammation-associated comorbidities, including cardiovascular diseases (CVDs). Yet sparse data exist on patterns over time in cardiovascular mortality for chronic infectious and inflammatory conditions. We used data from the Centers for Disease Control and Prevention 1999-2018 Multiple Causes of Death database to investigate patterns in CVD mortality from January 1, 1999 to December 31, 2018 in several infectious and inflammatory conditions. Specifically, we determined age-adjusted proportionate CVD mortality separately for patients with the following conditions (as well as the general population): hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel diseases (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Proportionate CVD mortality differed significantly in 1999 and 2018 for each condition compared with the general population (p < 0.0001). Proportionate CVD mortality decreased steadily in the general population (40.9 to 30.6%) but increased for patients with HCV (7.0 to 10.2%) and HIV (1.9 to 6.7%). For IBD, PSO, RA, and SLE, proportionate CVD mortality initially decreased followed by plateauing or increasing rates. Underlying disease-specific pathophysiologies, changes in natural history, and competing risks of chronic end-organ diseases contributing to these differences merit further study.

Comparative Risk of Incident Coronary Heart Disease Across Chronic Inflammatory Diseases.

Background: Chronic inflammatory diseases (CIDs) are considered risk enhancing factors for coronary heart disease (CHD). However, sparse data exist regarding relative CHD risks across CIDs. Objective: Determine relative differences in CHD risk across multiple CIDs: psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), systemic sclerosis (SSc), and inflammatory bowel disease (IBD). Methods: The cohort included patients with CIDs and controls without CID in an urban medical system from 2000 to 2019. Patients with CIDs were frequency-matched with non-CID controls on demographics, hypertension, and diabetes. CHD was defined as myocardial infarction (MI), ischemic heart disease, and/or coronary revascularization based on validated administrative codes. Multivariable-adjusted Cox models were used to determine the risk of incident CHD and MI for each CID relative to non-CID controls. In secondary analyses, we compared CHD risk by disease severity within each CID. Results: Of 17,049 patients included for analysis, 619 had incident CHD (202 MI) over an average of 4.4 years of follow-up. The multivariable-adjusted risk of CHD was significantly higher for SLE [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.2, 3.2] and SSc (HR 2.1, 95% CI 1.2, 3.9). Patients with SLE also had a significantly higher risk of MI (HR 3.6, 95% CI 1.9, 6.8). When CIDs were categorized by markers of disease severity (C-reactive protein for all CIDs except HIV, for which CD4 T cell count was used), greater disease severity was associated with higher CHD risk across CIDs. Conclusions: Patients with SLE and SSc have a higher risk of CHD. CHD risk with HIV, RA, psoriasis, and IBD may only be elevated in those with greater disease severity. Clinicians should personalize CHD risk and treatment based on type and severity of CID.

Long-Term Trajectories of Left Ventricular Ejection Fraction in Patients With Chronic Inflammatory Diseases and Heart Failure: An Analysis of Electronic Health Records.

BACKGROUND: Immune regulation and inflammation play a role in the pathogenesis and progression of acute and chronic heart failure (HF). Although the clinical course of acute, severe inflammatory cardiomyopathy is well described, the effects of chronic systemic inflammation on cardiovascular function over time are less clear. To investigate this question, we compared trajectories over time in left ventricular ejection fraction for patients with HF with different chronic inflammatory diseases (CIDs): HIV, systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, inflammatory bowel disease, and/or psoriasis. METHODS: Using a database of patients receiving care in a large metropolitan health care system since January 1, 2000, we analyzed serial, clinically indicated echocardiograms from patients with HF with CIDs and frequency-matched patients with HF without CIDs. We included patients with ≥3 serial echocardiograms (N=974; median 6.1 years between first and most recent echo). We assessed left ventricular ejection fraction trajectories over time using latent trajectory models, then investigated differences in left ventricular ejection fraction trajectories for specific CID subtypes compared with controls. RESULTS: Overall, the majority of patients studied (N=687; 70.5%) had left ventricular ejection fraction trajectories consistent with HF with preserved or midrange EF, whereas 255 (26.2%) had HF with reduced EF and 32 (3.3%) had HF with recovered EF. Compared with non-CID controls with HF, patients with rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus were significantly more likely than controls to have HF with preserved or midrange EF whereas patients with HIV were significantly more likely to have HF with reduced EF. CONCLUSIONS: Among patients with HF with CIDs, distinct left ventricular ejection fraction trajectory patterns associate with different specific individual CIDs. This highlights the heterogeneity of HF subtypes and changes over time across different CIDs.

Association between Ambient Temperature and Severe Diarrhoea in the National Capital Region, Philippines.

Epidemiological studies have quantified the association between ambient temperature and diarrhoea. However, to our knowledge, no study has quantified the temperature association for severe diarrhoea cases. In this study, we quantified the association between mean temperature and two severe diarrhoea outcomes, which were mortality and hospital admissions accompanied with dehydration and/or co-morbidities. Using a 12-year dataset of three urban districts of the National Capital Region, Philippines, we modelled the non-linear association between weekly temperatures and weekly severe diarrhoea cases using a two-stage time series analysis. We computed the relative risks at the 95th (30.4 °C) and 5th percentiles (25.8 °C) of temperatures using minimum risk temperatures (MRTs) as the reference to quantify the association with high- and low-temperatures, respectively. The shapes of the cumulative associations were generally J-shaped with greater associations towards high temperatures. Mortality risks were found to increase by 53.3% [95% confidence interval (CI): 29.4%; 81.7%)] at 95th percentile of weekly mean temperatures compared with the MRT (28.2 °C). Similarly, the risk of hospitalised severe diarrhoea increased by 27.1% (95% CI: 0.7%; 60.4%) at 95th percentile in mean weekly temperatures compared with the MRT (28.6 °C). With the increased risk of severe diarrhoea cases under high ambient temperature, there may be a need to strengthen primary healthcare services and sustain the improvements made in water, sanitation, and hygiene, particularly in poor communities.

Association of immune cell subsets with cardiac mechanics in the Multi-Ethnic Study of Atherosclerosis.

BackgroundImmunomodulatory therapy may help prevent heart failure (HF). Data on immune cells and myocardial remodeling in older adults with cardiovascular risk factors are limited.MethodsIn the Multi-Ethnic Study of Atherosclerosis cohort, 869 adults had 19 peripheral immune cell subsets measured and underwent cardiac MRI during the baseline exam, of which 321 had assessment of left ventricular global circumferential strain (LV-GCS). We used linear regression with adjustment for demographics, cardiovascular risk factors, and cytomegalovirus serostatus to evaluate the cross-sectional association of immune cell subsets with left ventricular mass index (LVMI) and LV-GCS.ResultsThe average age of the cohort was 61.6 ± 10.0 years and 53% were women. Higher proportions of γ/δ T cells were associated with lower absolute (worse) LV-GCS (-0.105% [95% CI -0.164%, -0.046%] per 1 SD higher proportion of γ/δ T cells, P = 0.0006). This association remained significant after Bonferroni's correction. Higher proportions of classical monocytes were associated with worse absolute LV-GCS (-0.04% [95% CI -0.07%, 0.00%] per 1 SD higher proportion of classical monocytes, P = 0.04). This did not meet significance after Bonferroni's correction. There were no other significant associations with LV-GCS or LVMI.ConclusionPathways associated with γ/δ T cells may be potential targets for immunomodulatory therapy targeted at HF prevention in populations at risk.FundingContracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and grant R01 HL98077 from the National Heart, Lung, and Blood Institute/NIH and grants KL2TR001424, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences/NIH.