Multivariable-adjusted Models Research Articles

Apolipoprotein ɛ4 is associated with increased risk of fall- and fracture-related hospitalisation: the Perth Longitudinal Study of Ageing Women.

Apolipoprotein ɛ4 (APOE ɛ4) may be a genetic risk factor for reduced bone mineral density (BMD) and muscle function, which could have implications for fall and fracture risk. We examined the association between APOE ɛ4 status and long-term fall- and fracture-related hospitalisation risk in older women. 1276 community-dwelling women from the Perth Longitudinal Study of Ageing Women (mean age ± SD = 75.2 ± 2.7 years) were included. At baseline, women underwent APOE genotyping and detailed phenotyping for covariates including prevalent falls and fractures, as well as health and lifestyle factors. The association between APOE ɛ4 with fall-, any fracture-, and hip fracture-related hospitalisations, obtained over 14.5 years from linked health records, were examined using multivariable-adjusted Cox-proportional hazard models. Over 14.5 years, 507 (39.7%) women experienced a fall-related hospitalisation, 360 (28.2%) women experienced a fracture-related hospitalisation, including 143 (11.2%) attributed to a hip fracture. In multivariable-adjusted models, compared to non-carriers, APOE ɛ4 carriers (n=297, 23.3%) had greater risk for a fall- (HR 1.48 95%CI 1.22-1.81), fracture- (HR 1.28, 95%CI 1.01-1.63) or hip fracture-related hospitalisation (HR 1.83 95%CI 1.29-2.61). The estimates remained similar when specific fall and fracture risk factors (fear of falling, plasma 25-hydroxyvitamin D, grip strength, timed-up-and-go, hip BMD, vitamin K status, prevalent diabetes, HbA1c, cholesterol, abbreviated mental test score) were added to the multivariable model. In conclusion, APOE ɛ4 is a potential risk factor for fall- and fracture-related hospitalisation in community-dwelling older women. Screening for APOE ɛ4 could provide clinicians an opportunity to direct higher risk individuals to appropriate intervention strategies.

Higher plant-derived nitrate intake is associated with lower odds of frailty in a cross-sectional study of community-dwelling older women.

Dietary nitrate intake is inversely related to numerous contributors towards frailty, including cardiovascular disease and poor physical function. Whether these findings extend to frailty remain unknown. We investigated if habitual nitrate intake, derived from plants or animal-based foods, was cross-sectionally associated with frailty in women. Community-dwelling older Australian women (n = 1390, mean age 75.1 ± 2.7 years) completed a validated semi-quantitative food frequency questionnaire (FFQ). Nitrate concentrations in food were obtained from international nitrate databases. We adopted the Rockwood frailty index (FI) of cumulative deficits comprising 33 variables across multiple health domains (scored 0 to 1), which predicts increased hospitalisation and mortality risk. A FI ≥ 0.25 indicated frailty. Cross-sectional associations between nitrate intake (total plant and animal nitrate, separately) and frailty were analysed using multivariable-adjusted logistic regression models (including lifestyle factors), as part of restricted cubic splines. A non-linear inverse relationship was observed between total plant nitrate intake and frailty. Compared to women with the lowest plant nitrate intake (Quartile [Q]1), women with greater intakes in Q2 (OR 0.69 95%CI 0.56-0.84), Q3 (OR 0.67 95%CI 0.50-0.90) and Q4 (OR 0.66 95%CI 0.45-0.98) had lower odds for frailty. A nadir in the inverse association was observed once intakes reached ~ 64mg/d (median Q2). No relationship was observed between total animal nitrate and frailty. Community-dwelling older women consuming low amounts of plant-derived nitrate were more likely to present with frailty. Consuming at least one daily serving (~ 75g) of nitrate-rich green leafy vegetables may be beneficial in preventing frailty.

Evaluating the Factors Associated With Increased Risk of Self-Reported Ischemic Heart Disease in Patients With Arthritis

Introduction. Arthritis has increased systematic repercussions either by extra-articular manifestations or due to limited activities. Methods. In this study, we used the 2020 and 2021 Behavioral Risk Factor Surveillance System (BRFSS), a large, nationally representative, cross-sectional telephone survey. The data was divided into the participants having arthritis and no arthritis. Results represented as an odds ratio (OR) with a 95% confidence interval (CI). We used a multivariate-adjusted logistic regression model to analyze the results. Fisher’s t-test was used to compare between 2 groups. P-value < 0.05 was considered significant. Results. BRFSS survey results led to 835,452 participants included in the final analysis. Of the included participant, 267020 has arthritis, and 568432 do not. In the arthritis group, 38.7% were males, and 61.3% were females. We found that patients with arthritis have a higher prevalence of diabetes and stroke. Adjusted logistic regression analysis showed that patients with arthritis have higher odds of reporting ischemic heart disease (IHD) (OR = 1.05, 95% CI 1.05-1.05, p-value < 0.001). Also, poor health status (mental, general, and physical) patients are more likely to report IHD. Conclusion. Patients with arthritis are more likely to report IHD, which further increases in patients with poor health status.

Interacting and joint effects of triglyceride-glucose index and hypertension on stroke risk in middle-aged and older Chinese adults: a population-based prospective cohort study

BackgroundTriglyceride-glucose (TyG) index and hypertension were well-established risk factors for stroke. And TyG index was associated with hypertension. However, no prior study has investigated the interactive effects of the TyG index and hypertension on stroke. This study examined whether hypertension mediates associations of TyG index with incident stroke and the extent of interaction or joint relations of TyG index and hypertension with stroke in middle-aged and older Chinese adults.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative prospective cohort study initiated in 2011. This cohort study included 9,145 middle-aged and older Chinese adults without stroke at baseline. The eposures were TyG index and the logarithmized product of hypertension, as determined during the baseline health examination. The main outcome was self-reported physician-diagnosed stroke which followed up from June 1, 2011, to June 30, 2018.ResultsOf the 9,145 participants, 4,251 were men (46.5%); the mean (SD) age was 59.20 (9.33) years. During a median follow-up of 7.1 years, 637 (7.0%) participants developed stroke. In multivariable-adjusted models, the TyG index was significantly associated with the risk of hypertension [odds ratio (OR) per 1-SD increase, 1.29; 95% CI, 1.19–1.41] and stroke [hazard ratio (HR) per 1-SD increase, 1.16; 95% CI, 1.02–1.33]. Both multiplicative and additive interactions were observed between TyG index and hypertension on stroke (HR for multiplicative: 2.34, 95% CI, 1.57–3.48; Synergy index: 4.13, 95% CI, 2.73–6.25). Mediation analysis showed that 20.0% of the association between TyG index and stroke was mediated through hypertension.ConclusionsThis study suggests a synergistic effect of TyG index and hypertension on stroke, and a small proportion of the association between TyG index and stroke was mediated by hypertension, indicating the benefit of coordinated control strategies for both exposures.

Association between more complex special care needs and overweight status and adolescents' difficulty with dental caries.

Little is known about dental caries experience in adolescents with overweight and complex special health care needs (SHCNs). Adolescent data (10-17 years) from the 2016-2020 National Survey of Children's Health (n = 91,196) was analyzed. The sample was grouped into the following: more complex SHCN and overweight, more complex SHCN without overweight, less complex SHCN and overweight, less complex SHCN without overweight, no SHCN but with overweight, and neither SHCN nor overweight. A multivariable-adjusted logistic regression model was conducted. Adolescents with more complex SHCNs with (OR: 1.82, 95% CI: 1.44-2.30, p < 0.001) or without overweight (OR: 1.51, 95% CI: 1.30-1.76, p < 0.001) were at higher odds of experiencing dental caries compared to healthy adolescents. No significant associations were observed between adolescents with less complex or no SHCN regardless of the overweight status with healthy adolescents. Adolescents with more complex SHCNs, irrespective of overweight status, experienced a higher caries severity than adolescents with no SHCNs or overweight.

Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing.

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g., Mediterranean diet) and/or individual nutrients (e.g., vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n= 371) of the Three-City cohort-where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12years-we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI] = 1.07 [1.01, 1.14]), higher red meat (OR [95% CI] = 1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI] = 0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI] = 1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI] = 1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility.

Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study

BackgroundThere is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling.MethodsA total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening.ResultsAt baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan–Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041–1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223–1.983) for osteoporosis (P < 0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527–0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%.ConclusionsThe current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial

ObjectiveHeart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine...

Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type two diabetes: The Veterans Affairs Diabetes Trial

BackgroundIntensive glycemic control reduced the risk of coronary artery disease (CAD) events among White ACCORD study participants with the haptoglobin (Hp)2-2 phenotype, and not among participants without the Hp2-2 phenotype. It is unknown whether these results persist in a population with more severe diabetes. MethodsHaptoglobin phenotype was measured in 1746 (97 %) samples from the Veterans Affairs Diabetes Trial (VADT) randomized controlled trial. Multivariable-adjusted Cox regression models assessed the effect of intensive therapy on CAD risk among participants with and without the Hp2-2 phenotype separately and when stratified within pre-specified race/ethnicity-based subgroups. Time-varying (achieved) HbA1c data (<7.0 % or ≥8.0 % compared to 7.0–7.9, updated every 3 months) were also analyzed in relation to CAD risk within each phenotype. Results567 (32.5 %) participants had the Hp2-2 phenotype. Compared to standard therapy, intensive glycemic control was not associated with risk of CAD among participants with the non-Hp2-2 or the Hp2-2 phenotype or for any race/ethnicity-based group. Compared to HbA1c of 7.0–7.9 %, having HbA1c <7.0 % was not associated with CAD risk for either phenotype or among any race/ethnicity-based group. Having HbA1c ≥8.0 % was associated with an increased risk of CAD among Hispanic participants without the Hp2-2 phenotype (HR= 3.61, 95 % CI: 1.54–8.41, p-interaction=0.53). ConclusionThe effect of intensive glycemic therapy on CAD events was not dependent on Hp phenotype in the VADT study of veterans with severe diabetes who may represent a population where Hp phenotype information would not be useful for personalizing diabetes management. However, further research is needed to determine if these results are conclusive.

TPP1 is associated with risk of advanced precursors and cervical cancer survival.

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.

Is the MIND diet useful for polycystic ovary syndrome? A case-control study

BackgroundPolycystic ovary syndrome (PCOS) is the most prevalent cause of ovulatory infertility and endocrine abnormalities in reproductive-age women. Although the MIND diet has been introduced to improve brain function, evidence shows that the MIND diet is rich in beneficial food groups that can have a preventive effect on other metabolic disorders. The present study was conducted to investigate the association between adherence to the MIND diet and PCOS.MethodsThis age and BMI frequency-matched case-control study was conducted on 216 women between January 2018 and March 2019 in Yazd, Iran. PCOS was diagnosed based on Rotterdam criteria. Participants were selected by convenience sampling method. The validated 178-item food frequency questionnaire was used to assess the usual dietary intake. Logistic regression was used to estimate the association between the MIND diet and PCOS.ResultsThe findings of the present study showed a significant inverse association between adherence to the MIND diet and PCOS in the crude model (OR for T3 vs. T1: 0.12 (95% CI: 0.05–0.25), P-value < 0.001) and multivariable-adjusted model including energy intake, age, BMI, waist circumference, marital status, pregnancy history, drug use history, education and physical activity (OR for T3 vs. T1 = 0.08 (95% CI: 0.03–0.19), P-value < 0.001). Adherence to the MIND diet had a protective effect of 92%.ConclusionAlthough the results of the present study showed that higher adherence to the MIND diet is associated with a lower risk of PCOS, more studies are needed to confirm these findings in the future.

Retinal morphological differences in atypical Parkinsonism: A cross-sectional analysis of the AlzEye cohort

ObjectiveAtypical Parkinsonian syndrome (APS) describes a heterogeneous group of disorders mimicking the clinical presentation of Parkinson disease (PD) but with disparate natural history and pathophysiology. While retinal markers of PD are increasingly described, APS has been afforded less attention possibly owing to its lower prevalence. Here, we investigate retinal morphological differences in individuals with APS in a large real world cohort. MethodsWe conducted a cross-sectional analysis of the AlzEye study, a retrospective cohort where ophthalmic data of individuals attending Moorfields Eye Hospital between January 2008 and March 31st 2018 (inclusive) has been linked with systemic disease data through national hospital admissions. Retinal features were extracted from macula-centered color fundus photography (CFP) and optical coherence tomography (OCT) and compared between individuals with APS and those unaffected. Individuals with idiopathic PD were excluded. Retinal neural and vascular features were measured using automated segmentation and analyzed with multivariable-adjusted regression models. ResultsAmong a cohort of 91,170 patients, there were 51 patients with APS and 91,119 controls. Individuals with APS were older and more likely to have hypertension and diabetes mellitus. After adjusting for age, sex, hypertension and diabetes melitus, individuals with APS had a thinner ganglion cell-inner plexiform layer (-3.95 microns, 95% CI: −7.53, −0.37, p = 0.031) but no difference in other retinoneural or retinovascular indices. Optic nerve cup-to-disc ratio was similar between groups. ConclusionOur cross-sectional analysis of the AlzEye cohort reveals distinct retinal morphological characteristics in APS compared to healthy controls. The study notably identifies a thinner ganglion cell-inner plexiform layer in APS patients, without accompanying changes in the inner nuclear layer or significant alterations in retinovascular indices and optic nerve cup-disc ratio. These changes are distinct from those observed in PD, where thinning of the inner nuclear layer (INL) is a characteristic feature. SignificanceThese findings demonstrate a retinal phenotype in APS, markedly different from both healthy controls and idiopathic Parkinson's disease, highlighting the potential of retinal imaging in differentiating neurodegenerative disorders. By establishing a distinct retinal phenotype for APS, our findings underscore the potential of retinal imaging as a valuable, non-invasive diagnostic tool. This advancement is particularly significant for enhancing diagnostic accuracy, facilitating early detection, and offering a window into the underlying disease mechanisms in APS, thereby aiding in the development of targeted therapeutic interventions and personalized patient care strategies.

Factors associated with knowledge of hypertension risk factors and symptoms among Gambian women: A cross-sectional study based on the Gambia Demographic and Health Survey

BackgroundWe examined the factors associated with knowledge of hypertension risk factors and symptoms among Gambian women. MethodsThis cross-section study was based on 11, 865 female participants (aged 15–49 years) of The Gambia Demographic and Health Survey 2019–2020. We performed descriptive statistics, and multivariate-adjusted logistic regression models. ResultsOnly 34.89 % and 36.82 % of the participants knew at least one risk factor and symptom of hypertension, respectively. Women who had never measured their blood pressure had a reduced odds of knowing a hypertension risk factor (OR = 0.68; 95 %CI: 0.60–0.77; P < 0.01) and symptom (OR = 0.56; 95 %CI: 0.49–0.64; P < 0.01). Compared to women with higher education, those with no education had a lower odds of knowing a hypertension risk factor (OR = 0.18; 95 %CI: 0.12–0.27; P < 0.01) and symptom (OR = 0.32; 95 %CI: 0.23–0.45; P < 0.01). Similarly, women who never used the internet had reduced odds of mentioning a hypertension risk factor (OR = 0.55; 95 %CI: 0.48–0.61; P < 0.01) and symptom (OR = 0.61; 95 %CI: 0.54–0.69; P < 0.01). Those who never watched television had decreased odds of knowing a hypertension risk factor (OR = 0.74; 95 %CI: 0.63–0.86; P < 0.01) and symptoms (OR = 0.68; 95 %CI: 0.58–0.80; P < 0.01). Conclusion: Fewer women could mention at least one hypertension risk factor and symptom. We also found that knowledge of hypertension risk factors and symptoms was associated with education level and socio-economic status.

Appendectomy and Long-term Colorectal Cancer Incidence, Overall and by Tumor Fusobacterium nucleatum Status.

To test hypotheses that appendectomy history might lower long-term colorectal cancer risk and that the risk reduction might be strong for tumors enriched with Fusobacterium nucleatum, bacterial species implicated in colorectal carcinogenesis. The absence of the appendix, an immune system organ and a possible reservoir of certain pathogenic microbes, may affect the intestinal microbiome, thereby altering long-term colorectal cancer risk. Utilizing databases of prospective cohort studies, namely the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of appendectomy history with colorectal cancer incidence overall and subclassified by the amount of tumor tissue Fusobacterium nucleatum​​ (Fusobacterium animalis). We used an inverse probability weighted multivariable-adjusted duplication-method Cox proportional hazards regression model. During the follow-up of 139,406 participants (2,894,060 person-years), we documented 2811 incident colorectal cancer cases, of which 1065 cases provided tissue F. nucleatum analysis data. The multivariable-adjusted hazard ratio of appendectomy for overall colorectal cancer incidence was 0.92 (95% CI, 0.84-1.01). Appendectomy was associated with lower F. nucleatum-positive cancer incidence (multivariable-adjusted hazard ratio, 0.53; 95% CI, 0.33-0.85; P=0.0079), but not F. nucleatum-negative cancer incidence (multivariable-adjusted hazard ratio, 0.98; 95% CI, 0.83-1.14), suggesting a differential association by F. nucleatum status (Pheterogeneity=0.015). This differential association appeared to persist in various participant/patient strata including tumor location and microsatellite instability status. Appendectomy likely lowers the future long-term incidence of F. nucleatum-positive (but not F. nucleatum-negative) colorectal cancer. Our findings do not support the existing hypothesis that appendectomy may increase colorectal cancer risk.

Olive oil consumption is associated with lower cancer, cardiovascular and all-cause mortality among Italian adults: prospective results from the Moli-sani Study and analysis of potential biological mechanisms.

Olive oil consumption has been reportedly associated with lower mortality rates, mostly from cardiovascular diseases, but its potential impact on cancer death remains controversial. Moreover, biological mechanisms possibly linking olive oil consumption to mortality outcomes remain unexplored. We longitudinally analysed data on 22,892 men and women from the Moli-sani Study in Italy (follow-up 13.1 y), to examine the association of olive oil consumption with mortality. Dietary data were collected at baseline (2005-2010) through a 188-item FFQ, and olive oil consumption was standardised to a 10 g tablespoon (tbsp) size. Diet quality was assessed through a Mediterranean diet score. Multivariable-adjusted Cox proportional hazard models, also including diet quality, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The potential mediating role of inflammatory, metabolic, cardiovascular and renal biomarkers on the association between olive oil intake and mortality was evaluated on the basis of change-in-estimate and associated p values. Multivariable HRs for all-cause, cancer, cardiovascular and other cause mortality associated with high (>3 tbsp/d) versus low (≤1.5 tbsp/d) olive oil consumption were 0.80 (0.69-0.94), 0.77 (0.59-0.99), 0.75 (0.58-0.97) and 0.97 (0.73-1.29), respectively. Taken together, the investigated biomarkers attenuated the association of olive oil consumption with all-cause and cancer mortality by 21.2% and 13.7%, respectively. Higher olive oil consumption was associated with lower cancer, cardiovascular and all-cause mortality rates, independent of overall diet quality. Known risk factors for chronic diseases only in part mediated such associations suggesting that other biological pathways are potentially involved in this relationship.

Use of medical therapy and risk of clinical events according to frailty in heart failure patients-A real-life cohort study.

Although recent randomized clinical trials have demonstrated the advantages of heart failure (HF) therapy in both frail and not frail patients, there is insufficient information on the use of HF therapy based on frailty status in a real-world setting. The aim was to examine how frailty status in HF patients associates with use of HF therapy and with clinical outcomes. Patients with new-onset HF between 2014 and 2021 were identified using the nationwide Danish registers. Patients across the entire range of ejection fraction were included. The associations between frailty status (using the Hospital Frailty Risk Score) and use of HF therapy and clinical outcomes (all-cause mortality, HF hospitalization, and non-HF hospitalization) were evaluated using multivariable-adjusted Cox models adjusting for age, sex, diagnostic setting, calendar year, comorbidities, pharmacotherapy, and socioeconomic status. Of 35 999 participants (mean age 69.1 years), 68% were not frail, 26% were moderately frail, and 6% were severely frail. The use of HF therapy was significantly lower in frailer patients. The hazard ratio (HR) for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation was 0.74 (95% confidence interval 0.70-0.77) and 0.48 (0.43-0.53) for moderate frailty and severe frailty, respectively. For beta-blockers, the corresponding HRs were 0.74 (0.71-0.78) and 0.51 (0.46-0.56), respectively, and for mineralocorticoid receptor antagonists, 0.83 (0.80-0.87) and 0.58 (0.53-0.64), respectively. The prevalence of death and non-HF hospitalization increased with frailty status. The HR for death was 1.55 (1.47-1.63) and 2.32 (2.16-2.49) for moderate and severe frailty, respectively, and the HR for non-HF hospitalization was 1.37 (1.32-1.41) and 1.82 (1.72-1.92), respectively. The association between frailty status and HF hospitalization was not significant (HR 1.08 [1.02-1.14] and 1.08 [0.97-1.20], respectively). In real-world HF patients, frailty was associated with lower HF therapy use and with a higher incidence of clinical outcomes including mortality and non-HF hospitalization.

Abstract PO2-02-04: The Impact of Statins on Breast Cancer Specific Mortality in a Diverse Patient Population with Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer

Abstract Hormone receptor-positive (HR+), HER2 negative (HER2−) breast cancer has a long-term risk of recurrence, compared with other breast cancer subtypes, which ultimately impacts mortality outcomes. Although adjuvant endocrine therapy plays an integral role in risk reduction, disparities persist—with Black women experiencing higher mortality rates compared to White women. Multiple studies have demonstrated that statin use can lead to a reduction in breast cancer mortality, but there is limited information in relation to the impact of statins among diverse patient populations in the United States. To assess whether statin use is associated with an improvement in breast cancer-specific mortality (BCSM), we conducted a large, observational study in women aged 66 and older diagnosed with Stage I–IIIC HR+, HER2- breast cancer between 2013 and 2017. We identified eligible women using the SEER-Medicare database and linked them to the BRIDGE (BReast cancer Investigation of Disparities in GEorgia) cohort, a survivorship cohort of the Georgia Cancer Registry. Patients needed to be continuously enrolled in Medicare Parts A, B, and D in the 12 months following a breast cancer diagnosis. We used Cox proportional hazards models to estimate the impact of statin use within 12 months of diagnosis on BCSM with adjustment for age, stage, and race using multivariable-adjusted hazard ratios (HRs). A total of 2483 participants were identified, and of those, 303 (12.2%) were statin users, 383 (15.4%) were non-Hispanic Black women, and 1564 (63%) resided in census tract with greater than or equal to 10% poverty levels at the time of diagnosis. Distribution of age, stage, and race were similar between statin and non-statin users. Of the statin users, 41/303 (13.5%) were non-Hispanic Black women. The majority of statin users were prescribed lipophilic statins alone (169; 55.8%), and atorvastatin was the most commonly prescribed statin. There was no association between statin use and BCSM (HR 1.09; 95% CI 0.62-1.90) in the multivariable-adjusted model. Although preliminary results suggest that there is no association between statin use and BCSM among women with Stage I–IIIC HR+, HER2− breast cancer, further analyses are planned to explore statin use as a time-varying exposure, which may provide additional insights into the potential relationship between statin use and BCSM. In addition, analyses examining potential heterogeneity by race, tumor and treatment characteristics, and comorbidities are forthcoming. Given the low cost and relative accessibility of statins, we anticipate these findings will inform the clinical management of women with operable breast cancer, increasing parity in outcomes and potentially narrowing race disparities. Citation Format: Ruth Sacks, Maya Bliss, Micah Streiff, Leah Moubadder, Maret Maliniak, Tsion Armidie, Lindsay Collin, Kevin Kalinsky, Lauren McCullough. The Impact of Statins on Breast Cancer Specific Mortality in a Diverse Patient Population with Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-04.

Postoperative venous thromboembolism risk in patients with vulvar carcinoma: An analysis of the National surgical Quality Improvement Program (NSQIP) database

ObjectivesDue to low incidence of vulvar cancer (VC), incidence and predictors for development of venous thromboembolism (VTE) are poorly understood. We examined incidence and risk factors associated with VTE in patients undergoing surgery for VC. MethodsWe included patients who underwent surgery for VC from the National Surgical Quality Improvement Program database. VTE within the 30-day postoperative period was captured with Current Procedural Terminology codes. Baseline demographics and clinical characteristics were compared between patients with and without VTE. Univariable and multivariable-adjusted exact logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and VTE. ResultsWe identified 1414 patients undergoing procedures for VC from the NSQIP database. Overall, 11 (0.8 %) patients developed VTE. Univariable predictors of VTE included surgery type [compared with simple vulvectomy: radical vulvectomy only (OR = 7.97, 95 % CI = 1.44, infinity) and radical vulvectomy plus unilateral IFN (OR = 15.98, 95 % CI = 2.70, infinity)], unplanned readmission (OR = 11.56, 95 % CI = 2.74, 46.38), deep surgical site infection (OR = 16.05, 95 % CI = 1.59–85.50), and preoperative thrombocytosis (OR = 6.53, 95 % CI = 0.00, 34.86). In a multivariable-adjusted model, longer operative time (≥72 min OR = 11.33, 95 % CI = 1.58–499.03) and preoperative functional status [compared with complete independence: total dependence (OR = 53.88, 95 % CI = 0.85, infinity) and partial dependence (OR = 53.88, 95 % CI = 0.85, infinity)] were associated with VTE. ConclusionIn this cohort of patients with VC undergoing radical vulvectomy, VTE incidence was low. Surgery type, longer operative time, dependent functional status, and wound disruption were identified as risk factors. Our findings highlight opportunities for prophylactic intervention in certain patients.

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers during Childhood and Adolescence

To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. Project Viva is a prospective pre-birth cohort (n = 2,128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used two-step oral glucose challenge testing to screen for gestational diabetes mellitus (GDM). In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n=1107), early adolescence (n=1027), and mid-adolescence (n=693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for pre-pregnancy body mass index (BMI). At mid-adolescence (17.1 [0.8] years old), offspring of mothers with GDM (n=27) had a higher BMI z-score (β; 95%Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (HOMA-IR, 0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, (HOMA-IR), and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated towards the null after adjustment for maternal pre-pregnancy BMI. Exposure to GDM is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peri-pubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Dietary patterns and the risk of diabetes in Korean adults: a cross-sectional and prospective cohort study

ObjectiveThis study aims to identify dietary patterns associated with diabetes in Korean adults and to investigate their association with diabetes risk in both a cross-sectional and prospective study. MethodsPredefined food groups collected by the Korea National Health and Nutrition Examination Survey (KNHANES 2015–2018, n = 19,721) were entered in a reduced rank regression (RRR) model, followed by stepwise linear regression analyses to identify the most predictive dietary patterns. We evaluated the construct validity of dietary patterns in two independent samples from KNHANES 2019−2021 (n = 14,223) and the Health Examinees (HEXA) cohort study (n = 30,013). Associations between dietary patterns and diabetes risk were examined using multivariable regression and multivariable-adjusted Cox proportional hazard models, respectively. ResultsA dietary pattern was identified with high positive loadings for refined white rice, kimchi and salted vegetables, wheat flour and bread, and seasonings, and high negative loadings for whole grains, legumes with tofu and soymilk, poultry, eggs, and plant oils. The higher pattern scores were significantly associated with diabetes risk in KNHANES 2015–2018 (male: odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.35, 1.88; female: OR: 1.37; 95% CI: 1.18, 1.52), KNHANES 2019−2021 (male: OR: 1.47; 95% CI: 1.01, 1.69; female: OR: 1.37; 95% CI: 1.18, 1.54), and HEXA study (male: hazard ratio [HR]: 1.10; 95% CI: 1.01, 1.34; female: HR: 1.24; 95% CI: 1.02, 1.52). ConclusionsDietary patterns derived by RRR followed by stepwise linear regression analyses were associated with increased risks of diabetes among Korean adults.