Age-adjusted Hazard Ratio Research Articles

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

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

Association of Social Determinants and Tumor Biology With Racial Disparity in Survival From Early-Stage, Hormone-Dependent Breast Cancer

Black women with hormone receptor-positive breast cancer experience the greatest racial disparity in survival of all breast cancer subtypes. The relative contributions of social determinants of health and tumor biology to this disparity are uncertain. To determine the proportion of the Black-White disparity in breast cancer survival from estrogen receptor (ER)-positive, axillary node-negative breast cancer that is associated with adverse social determinants and high-risk tumor biology. A retrospective mediation analysis of factors associated with the racial disparity in breast cancer death for cases diagnosed between 2004 and 2015 with follow-up through 2016 was carried out using the Surveillance, Epidemiology, and End Results (SEER) Oncotype registry. The study included women in the SEER-18 registry who were aged 18 years or older at diagnosis of a first primary invasive breast cancer tumor that was axillary node-negative and ER-positive, who were Black (Black), non-Hispanic White (White), and for whom the 21-gene breast recurrence score was available. Data analysis took place between March 4, 2021, and November 15, 2022. Census tract socioeconomic disadvantage, insurance status, tumor characteristics including the recurrence score, and treatment variables. Death due to breast cancer. The analysis with 60 137 women (mean [IQR] age 58.1 [50-66] years) included 5648 (9.4%) Black women and 54 489 (90.6%) White women. With a median (IQR) follow-up time of 56 (32-86) months, the age-adjusted hazard ratio (HR) for breast cancer death among Black compared with White women was 1.82 (95% CI, 1.51-2.20). Neighborhood disadvantage and insurance status together mediated 19% of the disparity (mediated HR, 1.62; 95% CI, 1.31-2.00; P < .001) and tumor biological characteristics mediated 20% (mediated HR, 1.56; 95% CI, 1.28-1.90; P < .001). A fully adjusted model that included all covariates accounted for 44% of the racial disparity (mediated HR, 1.38; 95% CI, 1.11-1.71; P < .001). Neighborhood disadvantage mediated 8% of the racial difference in the probability of a high-risk recurrence score (P = .02). In this study, racial differences in social determinants of health and indicators of aggressive tumor biology including a genomic biomarker were equally associated with the survival disparity in early-stage, ER-positive breast cancer among US women. Future research should examine more comprehensive measures of socioecological disadvantage, molecular mechanisms underlying aggressive tumor biology among Black women, and the role of ancestry-related genetic variants.

Long-Term Suicidal Ideation Profiles in Late-Life Depression and Their Association With Suicide Attempt or Death by Suicide.

Objective: In young and middle-aged adults, suicidal ideation is an important predictor of prospective suicide attempts, but its predictive power in late life remains unclear. In this study, we used Latent Profile Analysis (LPA) in a cohort of depressed older adults to identify distinct ideation profiles and their clinical correlates and test their association with risk of suicidal behavior longitudinally. Methods: A total of 337 depressed older adults (aged 50–93 years) were assessed for suicidal ideation and behavior for up to 14 years (median = 3 years), at least once per year (study period: 2002–2020). LPA was used, which derived 4 profiles of ideation scores based on subject-level aggregates. Groups were compared using analysis of variance (ANOVA) and χ2 tests at baseline and competing risk survival analysis during follow-up. Results: Ideation showed significant decline over time, on average (P < .001). LPA identified 4 suicidal ideation profiles. Risk of suicide attempt/death was higher for chronic severe ideators (age-adjusted hazard ratio = 5.75; 95% CI, 2.25–14.7; P < .001) and highly variable ideators (HR = 3.21; 95% CI, 1.03–10.1; P = .045) compared to fast-remitting ideators, despite comparable current ideation severity at baseline. Fast-remitting ideators had higher risk than low/non-ideators with no attempts or suicides (P < .001). Chronic severe ideators displayed the most severe dysfunction across personality, social characteristics, and impulsivity measures, whereas highly variable and fast-remitting ideators displayed specific deficits. Conclusions: Assessing suicidal ideation over months/years has clinical relevance, as it enabled the identification of distinct ideation patterns associated with substantive differences in clinical presentation and risk of future suicidal behavior despite similar ideation levels at baseline.

Thirty years of change in HIV incidence among adults in the Kyamulibwa General Population Cohort in rural southwest Uganda, 1989-2021

ObjectivesTo document the changes in HIV incidence over thirty years in Kalungu district, Uganda. MethodsSince 1989, residents aged ≥15 years old have been tested for HIV, and data were collected on HIV risk factors annually and later, biennially in the Kyamulibwa open cohort. In the 2019-2021 survey, people living with HIV self-reported on knowledge of their HIV status, antiretroviral therapy (ART) use, and their most recent viral load data were obtained from health facilities. The HIV seroconversion dates were randomly imputed between the last negative and first positive test dates using a uniform distribution. ResultsAmong 20,959 residents who were HIV-negative, 669 seroconverted within 176,659 person-years. Data showed a downward trend in age-adjusted HIV incidence over 30 years (P <0.001) even though HIV prevalence steadily increased with ART availability from 2004. Comparing 1990-1992 and 1996-1998, HIV incidence declined by 43% (0.79 to 0.45/100 person-years, P = 0.002). Between 1999 and 2011, the incidence remained stable at 0.49/100 person-years (95% confidence interval: 0.41-0.58) in men but slowly increased in women (average age-adjusted hazard ratio = 1.13 per 3 years, 95% confidence interval: 1.03-1.24; trend P-value = 0.02). After 2011, however, the incidence trends reversed and continued to decline in men and women and in all age groups. ConclusionFacilitating HIV testing and timely ART initiation, and supporting ART adherence must be emphasized alongside sustainable prevention measures.

COVID-19 severity and in-hospital mortality in an area with high HIV prevalence.

HIV infection causes immune dysregulation affecting T-cell and monocyte function, which may alter coronavirus disease 2019 (COVID-19) pathophysiology. We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area. We conducted a prospective observational cohort study in Tshwane, South Africa. Respiratory disease severity was quantified using the respiratory oxygenation score. Analysed biomarkers included inflammatory and coagulation biomarkers, CD4 T-cell counts, and HIV-1 viral loads (HIVVL). The analysis included 558 patients, of whom 21.7% died during admission. The mean age was 54 years. A total of 82 participants were HIV-positive. People living with HIV (PLWH) were younger (mean age 46 years) than HIV-negative people; most were on antiretroviral treatment with a suppressed HIVVL (72%) and the median CD4 count was 159 (interquartile range: 66-397) cells/µL. After adjusting for age, HIV was not associated with increased risk of mortality during hospitalisation (age-adjusted hazard ratio = 1.1, 95% confidence interval: 0.6-2.0). Inflammatory biomarker levels were similar in PLWH and HIV-negative patients. Detectable HIVVL was associated with less severe respiratory disease. In PLWH, mortality was associated with higher levels of inflammatory biomarkers. Opportunistic infections, and other risk factors for severe COVID-19, were common in PLWH who died. PLWH were not at increased risk of mortality and those with detectable HIVVL had less severe respiratory disease than those with suppressed HIVVL. This study advances our understanding of severe COVID-19 in PLWH.

Abstract C093: Historical redlining is associated with breast cancer subtype, stage at diagnosis and mortality

Abstract Background: Structurally racist policies have an important impact on health. The etiologic basis of racial disparities in aggressive forms of breast cancer is not well understood. Few studies have investigated the impact of structural racism as a potential driver of etiologic heterogeneity. We sought to estimate the effect of historic redlining on the development of aggressive subtypes and late-stage disease, and examine its role in breast cancer mortality. Methods: Using the Georgia Cancer Registry, we identified 921 non-Hispanic White (NHW) and 878 non-Hispanic Black (NHB) women residing in a Georgia Home Owners' Loan Corporation (HOLC) graded area with a first primary invasive breast cancer diagnosis in 2010–2017. Historic redlining scores for 2010 census tracts were calculated according to the proportion of HOLC grades within the tract. Historic redlining scores were examined continuously and dichotomized at &amp;lt;2.5, which represents areas that were historically considered low for investment risk (Green/“Best” or Blue/“Still Desirable”), vs. ≥2.5, which represents areas that were considered to be high risk (Yellow/“Definitely Declining” or Red/“Hazardous”). We used age-adjusted logistic regression to calculate case-only odds ratios (ORs) and 95% confidence intervals (CIs) associating historically high-risk redlined areas to a diagnosis of Luminal B, HER2, or Triple-Negative breast cancer (TNBC) compared with Luminal A tumors and a diagnosis of Stage II, III, or Stage IV breast cancer compared with Stage I disease. Additionally, we used Cox proportional hazards regression to calculate age-adjusted hazard ratios (HRs) and 95% CIs to associate historically high-risk areas with breast cancer mortality, overall and within each race strata. Results: Overall, 81% of NHB and 19% of NHW women lived in historically redlined census tracts. Women living in redlined areas were diagnosed with more aggressive subtypes (TNBC and HER2) and later stage (Stage III and IV) breast cancers. Compared with Luminal A breast cancer, the ORs for living in historically high-risk vs. low risk investment areas were 2.05 (95%CI=1.44, 2.93) for TNBC and1.49 (95%CI=0.89, 2.48) for HER2 disease. Compared with Stage I breast cancers, the ORs for historically high-risk vs. low risk investment areas were 1.85(95%CI=1.30, 2.63) for Stage III and 2.00 (95%CI=1.32, 3.02) for Stage IV breast cancer. Residing in historically high-risk census tracts was associated with a 1.68-fold increase in breast cancer mortality (95% CI=1.23, 2.30), after adjusting for age. The association was most pronounced among NHW women living in redlined census tracts (HR=1.36; 95%CI=0.99, 1.87); a near-null association was observed among NHB women (HR=0.97; 95% CI=0.78, 1.20). Conclusions: Historic redlining scores were associated with the diagnosis of more aggressive forms of breast cancer and breast cancer mortality. Historic place-based measures of structural racist policies have modern-day implications on health outcomes and may underpin reported disparities in aggressive or advanced tumor types. Citation Format: Jasmine M. Miller-Kleinhenz, Maret L. Maliniak, Micah J. Streiff, Leah Moubadder, Lauren E. Barber, Rebecca Nash, Lindsay J. Collin, Jeffrey M. Switchenko, Kevin C. Ward, Lauren E. McCullough. Historical redlining is associated with breast cancer subtype, stage at diagnosis and mortality [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C093.

Development and validation of genome-wide polygenic risk scores for predicting breast cancer incidence in Japanese females: a population-based case-cohort study.

This study aimed to develop an ancestry-specific polygenic risk scores (PRSs) for the prediction of breast cancer events in Japanese females and validate it in a longitudinal cohort study. Using publicly available summary statistics of female breast cancer genome-wide association study (GWAS) of Japanese and European ancestries, we, respectively, developed 31 candidate genome-wide PRSs using pruning and thresholding (P + T) and LDpred methods with varying parameters. Among the candidate PRS models, the best model was selected using a case-cohort dataset (63 breast cancer cases and 2213 sub-cohorts of Japanese females during a median follow-up of 11.9years) according to the maximal predictive ability by Harrell's C-statistics. The best-performing PRS for each derivation GWAS was evaluated in another independent case-cohort dataset (260 breast cancer cases and 7845 sub-cohorts of Japanese females during a median follow-up of 16.9years). For the best PRS model involving 46,861 single nucleotide polymorphisms (SNPs; P + T method with PT = 0.05 and R2 = 0.2) derived from Japanese-ancestry GWAS, the Harrell's C-statistic was 0.598 ± 0.018 in the evaluation dataset. The age-adjusted hazard ratio for breast cancer in females with the highest PRS quintile compared with those in the lowest PRS quintile was 2.47 (95% confidence intervals, 1.64-3.70). The PRS constructed using Japanese-ancestry GWAS demonstrated better predictive performance for breast cancer in Japanese females than that using European-ancestry GWAS (Harrell's C-statistics 0.598 versus 0.586). This study developed a breast cancer PRS for Japanese females and demonstrated the usefulness of the PRS for breast cancer risk stratification.

The Preventive Role of mRNA Vaccines in Reducing Death among Moderate Omicron-Infected Patients: A Follow-Up Study.

Very few studies have been conducted to assess the potential preventive role of vaccines, particularly mRNA vaccines, in the improvement of survival among moderate and severe hospitalized patients with COVID-19. After community-acquired outbreaks of the Omicron variant from 18 March until 31 May 2022, occurred in Taiwan, this retrospective cohort of 4090 moderate and 1378 severe patients admitted to hospital was classified according to whether they were administered an mRNA-based vaccine, and followed up to ascertain rates of death in both the vaccinated (≥2 doses) and unvaccinated (no or 1 dose) groups. The age-adjusted hazard ratio (aHR) of less than 1 was used to assess the preventive role of mRNA vaccines in reducing deaths among moderate and severe Omicron-infected patients. Survival was statistically significantly better for the ≥2 dose jab group (aHR, 0.75, 95% confidence interval [CI], 0.60 to 0.94) and even higher among those who had received a booster jab (aHR, 0.71; 95% CI, 0.55 to 0.91) compared with the unvaccinated group among moderate patients, but not among severe patients. In conclusion, unveiling the role of mRNA vaccines in preventing moderate but not severe COVID-19 patients from death provides new insights into how mRNA vaccines play a role in the pathway leading to a severe outcome due to Omicron COVID-19.

African American Race Is a Potential Favorable Biologic Factor That Impacts Clinical Outcome for Patients with Multiple Myeloma

Multiple myeloma (MM) remains an incurable malignancy characterized by plasma cells that are nurtured and proliferate within the permissive bone marrow milieu. It has a greater incidence in African Americans (AA) compared to whites (13.8 vs. 6.5/100,000). The five-year age adjusted mortality rate, according to SEER database, is greater in AA compared to white Pts (5.8 vs. 2.9/100,000), which is likely explained by a greater incidence in the AA population. However, recent reports have also shown that AAs with equal access to care have an even better survival than their white counterparts [Fiala et al. Cancer. 2017]. Conversely, results from the CoMMpass registry database showed that OS was shorter for AA compared with Whites (age-adjusted hazard ratio (HR) 1.7, 95% confidence interval 1.2-2.4, P = 0.003) [Derman et al. Blood Cancer J. 2020]. Here, we report the interplay of race and other dimensions of MM care using the National Cancer Database (NCDB). Methods: NCDB is the largest cancer database in the US including >70% of all newly diagnosed cancer patients. The International Classification of Diseases for Oncology (ICD-O) code of 9732 was used. OS was calculated from the date of MM diagnosis. Given that Smoldering MM (SMM) does not have specific ICD code, we defined patients who did not receive any treatment within 3 months after the diagnosis as SMM, similar to other authors (Ravindran et al. Blood Cancer J. 2016). Initiation of systemic treatment was considered as a surrogate of progression to symptomatic MM. Overall survival (OS) of SMM patients was calculated from initiation of systemic treatment after they progressed to MM, estimated by the Kaplan-Meier method, and compared with the log-rank test. Cumulative incidence of progression from SM to MM was calculated with death as a competing risk and compared with the Gray's test. Multivariable Cox and logistic regression analysis were performed to identify independent predictors of OS and progression to MM, respectively. Results: We identified 56,021 patients with MM and 11,485 with SMM between 2010 to 2014 in this database. Among MM patients, 42,836 (76%) were white and 11,255 (20%) self-identified as AA. For AA patients, there was a lower proportion of Medicare (46 vs. 56%), and private insurance (35 vs. 36%) and a higher percentage of Medicaid (11 vs. 5%) and uninsured Pts (6 vs. 3%) compared to Pts that self-identified as white. A larger proportion of AAs had a Charlson score ≥1 (30 vs. 24%, p<0.001). The percentage of Pts who underwent radiation was higher among whites compared to AA (23 vs 8%). However, unadjusted OS was greater for AA compared to white Pts, 55 vs. 48 months, respectively (P < 0.0001). Among SMM patients, 8,324 (72%) were white and 2,756 (24%) were AA. SMM was diagnosed in AA patients at a median of 3.7 years younger than in white patients. Similar socioeconomic disparities were observed in SMM as in MM cohort. The time from diagnosis of SMM to first therapy which is indicative of progression from SMM to MM is the same among AA and white (median time in days 136 vs 135 days, p=0.672) with comparable OS. Multivariable Cox and logistic regression analysis showed that lower age, AA race, Female gender, ASCT, living in a higher income area and having Medicare or Private insurance compared to no insurance were independent predictors for better OS in MM. Although other predictive factors persisted for patients with SMM, race did not reach statistical significance. Conclusion: Taken together, our results utilizing one of the largest available datasets in the US, reflect a similar outcome for AA and white patients with MM despite a clear disparity in healthcare access and SES. This finding might suggest a more favorable biology of the disease among AA Pts. The lower rate of radiation among AA is also an indirect measure of bone complications. AA enjoy less bone loss and fractures under physiologic and pathologic conditions. Further studies to elucidate the role of bony compartment of the MM microenvironment at the cellular and molecular levels might be able to explain this disparity and help advance a more personalized treatment options to improve outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Underweight and obesity are related to higher mortality in patients undergoing coronary angiography: The KARDIO invasive cardiology register study.

In patients with some cardiovascular disease conditions, slightly elevated body mass index (BMI) is associated with a lower mortality risk (termed "obesity paradox"). It is uncertain, however, if this obesity paradox exists in patients who have had invasive cardiology procedures. We evaluated the association between BMI and mortality in patients who underwent coronary angiography. We utilised the KARDIO registry, which comprised data on demographics, prevalent diseases, risk factors, coronary angiographies, and interventions on 42,636 patients. BMI was categorised based on WHO cut-offs or transformed using P-splines. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for all-cause mortality. During a median follow-up of 4.9 years, 4688 all-cause deaths occurred. BMI was nonlinearly associated with mortality risk: compared to normal weight category (18.5-25 kg/m2 ), the age-adjusted HRs (95% CIs) for all-cause mortality were 1.90 (1.49, 2.43), 0.96 (0.92, 1.01), 1.04 (0.99, 1.09), 1.08 (0.96, 1.20), and 1.45 (1.22, 1.72) for underweight (<18.5 kg/m2 ), preobesity (25 to <30 kg/m2 ), obesity class I (30 to <35 kg/m2 ), obesity class II (35 to <40 kg/m2 ), and obesity class III (>40 kg/m2 ), respectively. The corresponding multivariable adjusted HRs (95% CIs) were 2.00 (1.55, 2.58), 0.92 (0.88, 0.97) 1.01 (0.95, 1.06), 1.10 (0.98, 1.23), and 1.49 (1.26, 1,78), respectively. In patients undergoing coronary angiography, underweight and obesity class III are associated with increased mortality risk, and the lowest mortality was observed in the preobesity class. It appears the obesity paradox may be present in patients who undergo invasive coronary procedures.

Hospitalisation Is Prognostic of Survival in Chronic Thromboembolic Pulmonary Hypertension.

This analysis investigated the prognostic value of hospitalisation in chronic thromboembolic pulmonary hypertension (CTEPH) using data from the Czech Republic, wherein pulmonary endarterectomy (PEA) was the only targeted treatment option until 2015. Using a landmark method, this analysis quantified the association between a first CTEPH-related hospitalisation event occurring before 3-, 6-, 9-, and 12-month landmark timepoints and subsequent all-cause mortality in adult CTEPH patients diagnosed between 2003 and 2016 in the Czech Republic. Patients were stratified into operable and inoperable, according to PEA eligibility. CTEPH-related hospitalisations were defined as non-elective. Hospitalisations related to CTEPH diagnosis, PEA, balloon pulmonary angioplasty, or clinical trial participation were excluded. Of 436 patients who survived to ≥3 months post diagnosis, 309 were operable, and 127 were inoperable. Sex- and age-adjusted hazard ratios (HRs) showed CTEPH-related hospitalisation was a statistically significant prognostic indicator of mortality at 3, 9, and 12 months in inoperable patients, with an approximately 2-fold increased risk of death in the hospitalisation group (HRs [95% CI] ranging from 1.98 [1.06–3.70] to 2.17 [1.01–4.63]). There was also a trend of worse survival probabilities in the hospitalisation groups for operable patients, with the difference most pronounced at 3 months, with a 76% increased risk of death (adjusted HR [95% CI] 1.76 [1.15–2.68]). This first analysis on the prognostic value of CTEPH-related hospitalisations demonstrates that a first CTEPH-related hospitalisation is prognostic of mortality in CTEPH, particularly for inoperable patients. These patients may benefit from medical and/or interventional therapy.

The effect of paternal and maternal factors on the prognosis of live birth in couples with recurrent pregnancy loss.

Currently, recurrent pregnancy loss (RPL) examinations focus on the woman, although paternal factors are also involved. Men in couples with RPL have higher sperm DNA fragmentation levels than fertile men, but the effect of sperm DNA damage on couple's later prognosis is unknown. Advanced maternal age and obesity are associated with RPL, but paternal lifestyle factors are less studied. Therefore, we aimed to study the associations of couples' lifestyle factors, causes of RPL, and sperm DNA fragmentation with their prognosis of future live birth. This descriptive cohort study comprised 506 couples investigated for RPL at Helsinki University Hospital, Finland, between 2007 and 2016, linked with national health and population registers. The primary outcome was couple's live birth after RPL investigations. Data on couple's background factors, including age, body mass index, smoking, and alcohol use, were collected from medical records. Sperm DNA fragmentation index was analyzed from 211 men using the sperm chromatin dispersion test. The associations between background factors, sperm DNA fragmentation, and cumulative probability of live birth over time were analyzed using cross-tabulations and age-adjusted Cox regression. In all, 352 of 506 couples (69.6%) achieved live birth. Maternal age, unexplained RPL, prolonged pregnancy attempts before investigations, paternal obesity, and maternal smoking were associated with prognosis: unadjusted hazard ratio for couple's live birth for women aged 35-39 vs younger than 30 years was 0.63 (95% confidence interval [CI] 0.47-0.84), and for 40 years or older was 0.36 (95% CI 0.22-0.58). Age-adjusted hazard ratio for unexplained vs explained RPL was 1.39 (95% CI 1.12-1.72), for couple's pregnancy attempt at least 4 years vs less than 2 years was 0.50 (95% CI 0.33-0.76), for paternal body mass index at least 30 kg/m2 vs less than 25 kg/m2 was 0.67 (95% CI 0.46-0.98), and for maternal smoking was 0.71 (95% CI 0.51-0.99). Altogether, 96/135 (71.1%) couples with normal (<15%), 38/60 (63.3%) with intermediate (15-30%), and 11/16 (68.8%) with high sperm DNA fragmentation index achieved live birth (p =0.56). In couples with RPL, prolonged pregnancy attempts, a cause found in RPL examinations, lifestyle factors, and maternal age are negatively associated with their prognosis of future live birth. Sperm DNA fragmentation was not associated, but the number of men with damaged spermatozoa was small. We suggest that clinicians include women and men in RPL counseling because couple's joint lifestyle seems to determine their later prognosis.

Trends in mortality and ischemic outcomes in patients with ST-segment elevation myocardial infarction following implementation of a primary percutaneous coronary intervention strategy, 2003–2017

Abstract Introduction In Denmark, primary percutaneous coronary intervention (pPCI) has served as the national reperfusion strategy in ST-segment elevation myocardial infarction (STEMI) since 2003. Since then, extensive changes in management and treatment of patients with STEMI have been introduced. We investigated the temporal trends in one-year mortality and ischemic outcomes after STEMI. Methods We included all first-time STEMI patients treated with pPCI in Western Denmark from 2003 to 2017. Patients were categorized into four time periods based on year of pPCI treatment (2003–2006, 2007–2010, 2011–2014, 2015–2017) and followed for one year. Outcomes included all-cause death, recurrent myocardial infarction (MI: follow-up started after 30 days post-pPCI since the validity of recurrent MI is low in the first 30 days), and ischemic stroke. We also identified a sex and age matched comparison cohort without prior cardiovascular disease from the Western Denmark general population. Groups were compared using sex- and age-adjusted hazard ratios (aHRs) by Cox regression with the first period as reference. Results A total of 18,538 STEMI patients and 92,690 individuals from the general population were included. One-year mortality in STEMI patients decreased from 10.8% in 2003–2006 to 7.8% in 2015–2017 (aHR 0.70, 95% CI 0.60–0.80), while it was steady in the general population cohort (figure). The one-year risk of recurrent MI and ischemic stroke also decreased from 2003–2006 to 2015–2017 (MI: 3.5% vs. 2.4%, aHR: 0.66, 95% CI 0.51–0.86; ischemic stroke: 2.5% vs. 1.9%, aHR 0.58, 95% CI 0.42–0.80). These improvements coincided with increased up-take of evidence-based treatments, especially drug-eluting stents (39% vs. 90%), high-intensity statins (3% vs. 87%), and newer antiplatelet agents. Conclusions From 2003 to 2017, the one-year risk of death, recurrent MI, and ischemic stroke decreased substantially among patients with STEMI. These improvements occurred simultaneously with the gradual implementation of evidence-based guideline-directed treatments. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Aase and Ejnar Danielsen foundation

Dissociation between two-dimensional and three-dimensional echocardiography – clinical implications

Abstract Objectives To investigate the agreement between two-dimensional (2DE) and three-dimensional echocardiography (3DE) in a general population, along with clinical impact of the differences. Background Left ventricular ejection fraction (LVEF) has prognostic value and is used to guide cardiac treatment. The preferred technique is two-dimensional (2D) echo, although three-dimensional (3D) echo is more accurate when compared to MRI. Our study evaluates the agreement between 2D and 3D LVEF and the potential clinical impact of disagreements. Methods Study population ware participants from the Copenhagen City Heart Study, who underwent 2DE and 3DE between 2011–2014. Means of difference (MD) were assessed in participant groups with a LVEF below 40%, 40–50%, and above 50%. Age-adjusted Cox proportional hazard ratios (HR) were calculated for all-cause mortality, major adverse cardiovascular event (MACE) and cardiac event of any kind. Results In total 2554 participants from the Copenhagen City Heart Study were included. Median age was 58.3 (IQR: 44.2–69.8) years and 1137 (44.5%) were male. Mean LVEF in 2D was 56.6% (95% CI: 56.4–56.9%) and 52.0% (95% CI: 51.7–52.4%) in 3D, p&amp;lt;0.05. MD increased the further LVEF deteriorated: −14.9% (95% CI: −16.0 to −13.9%) (LVEF &amp;lt;40%), −9.3% (95% CI: −9.8 to −8.9%) (LVEF 40–50%) and −1.2% (95% CI: −1.6 to −0.9%) (LVEF ≥50%). 2DE overestimated the LVEF relative to 3D in 1824 (71.4%) instances. 3D LVEF &amp;lt;40% was associated with a HR for all-cause mortality of 2.58 (95% CI: 1.55–4.31, p&amp;lt;0.05), MACE: 1.90 (95% CI: 1.22–2.98, p&amp;lt;0.05) and cardiovascular event: 1.61 (95% CI: 1.04–2.48, p&amp;lt;0.05). HR for 2D LVEF &amp;lt;40% 0.84 (95% CI: 0.21–3.41, p=0.80) (all-cause), 3.12 (95% CI: 1.64–5.94, p&amp;lt;0.05) (MACE) and 2.68 (95% CI: 1.42–5.09, p&amp;lt;0.05) (cardiovascular event). Conclusion With declining LVEF, 2D echo is prone to significantly overestimate LVEF and a 3D LVEF less than 40% is associated with excess all-cause mortality but less with MACE and cardiovascular events when compared to 2D LVEF. Funding Acknowledgement Type of funding sources: None.

Mortality Patterns of Synchronous Uterine and Ovarian Cancers: A SEER Registry Analysis.

The degree to which uterine cancer metastatic to the ovary is misdiagnosed as synchronous stage I uterine and ovarian cancers is unclear. We sought to determine whether patients with synchronous cancers had mortality patterns similar to either stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. The Surveillance, Epidemiology, and End Results database was used to compare mortality of patients with synchronous stage I uterine and stage I ovarian cancers versus those with stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. We calculated age-adjusted mortality hazard ratios (HR) and 95% confidence intervals (CI) accounting for calendar year and grade, adjuvant treatment, grade 1 endometrioid cancers, grade 3 endometrioid cancers, and stage IA cancers. Among the 9,321 patients, we observed lower age-adjusted mortality in patients with stage I synchronous cancers (n = 937) compared to those with stage IIIA uterine (n = 531; HR, 0.45 95% CI, 0.35-0.58), stage I uterine (n = 6,919; HR, 0.74; 95% CI, 0.60-0.91), and stage I ovarian cancers (n = 934; HR, 0.52; 95% CI, 0.41-0.67). Results were similar after taking into account diagnosis year and grade, and limiting to those receiving adjuvant therapy, grade 1 or grade 3 endometrioid cancers, or stage IA cancers. We observed lower mortality for synchronous stage I uterine and ovarian cancers, which was not explained by younger age, earlier stage, lower grade, histology type, or adjuvant therapy. The possible misdiagnosis associated with clinicopathologic of synchronous uterine and ovarian cancers does not appear to worsen survival on a population level.

Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study.

Background:The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke.Methods:Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment.Results:Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%–42%]); possible 26 out of 151 (17% [12%–24%]); and uncertain 9 out of 43, (20% [10%–36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%–53%]); migraine aura 4 out of 38 (11% [3%–25%]); non-TIA focal symptoms 16 out of 99 (16% [10%–25%]); and no focal features 1 out of 29 (3% [0%–18%]). After MRI, a further 14 (5% [95% CI, 3–8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3–62]; P<0.0001).Conclusions:MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

A prospective cohort study of cigarette smoking, alcohol drinking and liver cancer incidence in Chinese men

Population-based prospective studies on the associations of cigarette smoking, alcohol drinking, and primary liver cancer remain limited in Mainland China. Our study was designed to evaluate such relationships in middle-aged Chinese men. Self-reported habits of cigarette smoking and alcohol drinking were obtained from all cohort members at the baseline survey. The outcomes were identified through in-person follow-up and annual record linkage to multiple statistics of vital and cancer registration. Age-adjusted and multivariable-adjusted hazard ratio (HR) and their corresponding 95% confidence interval (CI) were estimated utilizing the Cox regression model. After a median follow-up of 12.31 years, 329 cases of incident primary liver cancer occurred among 45 266 male participants. Compared with never smoker, former smoker was positively associated with liver cancer risk, with a multivariable-adjusted HR of 1.42 (95% CI 1.02-1.98). Individuals who had smoked for more than 40 years had a 49% increased risk of liver cancer (HR≥40 years 1.49, 95% CI 1.04-2.14). The association of alcohol drinking with liver cancer showed no statistical significance. Our study provided evidence that cigarette smoking was positively associated with an increased liver cancer risk among Chinese men. Attention to such non-viral modifiable risk factors to prevent liver cancer effectively is needed.

Twenty-Year Temporal Trends in Risk of Ischemic Stroke in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study.

We examined temporal trends in risk of first-time ischemic stroke in patients with incident type 2 diabetes mellitus (T2DM) and no prior atherosclerotic cardiovascular disease (ASCVD). Using nationwide health registries, we identified all patients with incident T2DM without a prior hospital diagnosis of ASCVD from 1996 to 2015 in Denmark. Patients were assigned to 5-year periods based on the date of T2DM diagnosis and were followed for 5 years. Each patient was matched by sex and age with up to three individuals from the general population. Temporal trends in ischemic stroke were examined using Cox regression to compute hazard ratios (HRs). Temporal use of prophylactic cardiovascular medications was also assessed. The study comprised 288,825 patients with incident T2DM and 782,232 general population individuals. From 1996-2000 to 2011-2015, the 5-year risk of first-time ischemic stroke was approximately halved in the T2DM cohort (5.2% vs. 2.7%; sex- and age-adjusted HR 0.52 [95% CI 0.49-0.55]). Patients diagnosed in 2011-2015 had increased risk of ischemic stroke compared with individuals in the general population; however, the risk difference narrowed over time (5.2% vs. 2.9% in 1996-1999 [difference 2.3%]; 2.7% vs. 2.0% in 2011-2015 [difference 0.7%]). Use of prophylactic cardiovascular medications increased markedly during the overall study period, especially use of statins (from 5% to 50%) and multiple antihypertensive drugs (from 18% to 33%). From 1996 to 2015, the 5-year risk of first-time ischemic stroke was approximately halved in patients with incident T2DM and no prior ASCVD, coinciding with markedly increased use of prophylactic cardiovascular medications.

Risk of cardiovascular disease in women and men with subfertility: the Trøndelag Health Study

To investigate the association between subfertility and risk of cardiovascular disease (CVD) outcomes. Prospective study. Population-based cohort. We studied 31,629 women and 17,630 men participating in the Trøndelag Health Study. Self-reported subfertility. As men were not directly asked about fertility, male partners of female participants were identified through linkage to the Medical Birth Registry of Norway and assigned the fertility information obtained from their partners. The primary outcomes were stroke and coronary heart disease in women and men with and without a history of subfertility. The secondary outcomes were myocardial infarction and angina (subgroups of coronary heart disease) and any CVD (stroke or coronary heart disease). Information on CVD was available by linkage to hospital records. We used Cox proportional hazards models adjusted for age at participation in the Trøndelag Health Study (linear + squared), birth year, smoking history, cohabitation, and education. Cardiometabolic factors were assessed in separate models. A total of 17% of women and 15% of men reported subfertility. In women, subfertility was modestly associated with an increased risk of stroke (age-adjusted hazard ratio [aaHR], 1.19; 95% confidence interval [CI], 1.02-1.39; adjusted hazard ratio [aHR]; 1.18; 95% CI, 1.01-1.37) and coronary heart disease (aaHR, 1.19; 95% CI, 1.06-1.33; aHR, 1.16; 95% CI, 1.03-1.30) compared with fertile women. In men, we observed a weak positive association for stroke (aaHR, 1.11; 95% CI, 0.91-1.34; aHR, 1.10; 95% CI, 0.91-1.33) and a weak inverse association for coronary heart disease (aaHR, 0.92; 95% CI, 0.81-1.05; aHR, 0.93; 95% CI, 0.81-1.06). We observed modestly increased risks of CVD outcomes in women and some weak associations in men, although with no strong statistical evidence on sex differences. We acknowledge that we were only able to include men linked to pregnancies ending at 12 completed gestational weeks or later, potentially resulting in selection bias and misclassification of history of subfertility in analyses of male partners. Despite the large sample size, our results indicate the need for larger studies to obtain precise results in both sexes and determine whether there are true sex differences.

Epidemiology, Healthcare Resource Utilization, and Mortality of Asthma and COPD in COVID-19: A Systematic Literature Review and Meta-Analyses

PurposeThere has been concern that asthma and chronic obstructive pulmonary disease [COPD] increase the risk of developing and exacerbating COVID-19. The effect of medications such as inhaled corticosteroids (ICS) and biologics on COVID-19 is unclear. This systematic literature review analyzed the published evidence on epidemiology and the burden of illness of asthma and COPD, and the use of baseline medicines among COVID-19 populations.Patients and MethodsUsing Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Embase®, MEDLINE® and Cochrane were searched (January 2019–August 2021). The prevalence of asthma or COPD among COVID-19 populations was compared to the country-specific populations. Odds ratios (ORs) were estimated to compare healthcare resource utilization (HCRU) rates, and meta-analyses of outcomes were estimated from age-adjusted ORs (aORs) or hazard ratios (aHRs). Meta-analyses of COVID-19 outcomes were conducted using random effects models for binary outcomes.ResultsGiven the number and heterogeneity of studies, only 183 high-quality studies were analyzed, which reported hospitalization, intensive care unit (ICU) admissions, ventilation/intubation, or mortality. Asthma patients were not at increased risk for COVID-19–related hospitalization (OR = 1.05, 95% CI: 0.92 to 1.20), ICU admission (OR = 1.21, 95% CI: 0.99 to 1.1.48), ventilation/intubation (OR = 1.24, 95% CI: 0.95 to 1.62), or mortality (OR = 0.85, 95% CI: 0.75 to 0.96). Accounting for confounding variables, COPD patients were at higher risk of hospitalization (aOR = 1.45, 95% CI: 1.30 to 1.61), ICU admission (aOR = 1.28, 95% CI: 1.08 to 1.51), and mortality (aOR = 1.41, 95% CI: 1.37 to 1.65). Sixty-five studies reported outcomes associated with ICS or biologic use. There was limited evidence that ICS or biologics significantly impacted the risk of SARS-CoV-2 infection, HCRU, or mortality in asthma or COPD patients.ConclusionIn high-quality studies included, patients with asthma were not at significantly higher odds for adverse COVID-19–related outcomes, while patients with COPD were at higher odds. There was no clear evidence that baseline medication affected outcomes.RegistrationPROSPERO (CRD42021233963).