Multivariable-adjusted HR Research Articles

The association of genetic susceptibility to smoking with cardiovascular disease mortality and the benefits of adhering to a DASH diet: The Singapore Chinese Health Study

Understanding the genetic predisposition to cardiovascular disease (CVD) may help to improve clinical intervention strategies. Lifestyle factors, such as diet, may differ among ethnic groups and may, in turn, modify individuals' risks to diseases. We examined the genetic predisposition to ever smoking in relation to CVD mortality and assessed whether such an association could be modified by dietary intake. A total of 23,760 Chinese adults from the Singapore Chinese Heath Study who were free of cancer and CVD at recruitment (1993-1998) were included in the study. A weighted genetic risk score (wGRS) was calculated to define the genetically determined regular smoking behavior (never or ever). Multivariable-adjusted Cox regression models were used to assess the association between the wGRS and CVD mortality. We also conducted a 1-sample Mendelian randomization analysis for ever smoking and CVD mortality. Over a mean of 22.6 years of follow-up, 2301 CVD deaths were identified. A genetic predisposition to ever smoking was significantly associated with CVD mortality; the multivariable-adjusted HR of CVD mortality was 1.07 (95% CI: 1.03-1.12), with a per-SD increment in the wGRS. However, the Mendelian randomization analysis did not support a causal relationship between ever smoking and CVD mortality (OR, 1.13; 95% CI: 0.87-1.45). Additionally, the Dietary Approaches to Stop Hypertension (DASH) score significantly modified the association between the smoking wGRS and CVD mortality; the association between a genetic predisposition to smoking and CVD mortality was only observed among individuals with a low DASH score (P-interaction = 0.004). A genetic predisposition to smoking was associated with CVD mortality in the Chinese population. In addition, we detected a significant interaction showing higher CVD mortality related to genetically determined smoking among those with lower DASH scores.

Associations between sleep status and risk for kidney stones in Chinese adults: a prospective cohort study

Objective: To analyze the associations between sleep status and the risk for kidney stone in Chinese adults. Methods: This study used baseline and long-term follow-up data of China Kadoorie Biobank. After excluding those with self-reporting of diagnosed chronic kidney disease and cancer and those with extreme values of sleep duration at baseline survey, 501 701 participants were included in this study. The information about their sleep status were collected, including insomnia symptoms, daytime sleepiness, nap habit, snoring and sleep duration. The sleep score was constructed based on insomnia symptoms, daytime sleepiness, and sleep duration, ranging from 0 to 3. Cox proportional hazards regression models were used to evaluate the association of sleep status with the risk for kidney stone, including individual sleep factors and combined sleep score. Results: During the follow-up for average (10.7±2.2) years, 12 381 cases of kidney stone were recorded for the first time. Compared with participants without insomnia symptoms, the multivariable-adjusted HR of kidney stone in those with difficulty falling asleep and waking up early were 1.12 (95%CI: 1.06-1.18) and 1.06 (95%CI: 1.00-1.12), respectively. There was no statistically significant association of kidney stone risk with sleeping pill use, daytime sleepiness, nap habit, or snoring. Compared with participants with sleep duration ≥7 hours per day, the HR of kidney stone in those with sleep duration <7 hours per day was 1.13 (95%CI: 1.08-1.18). Compared with participants with sleep score of 3 (highest sleep quality), the HR of kidney stone in those with sleep score of 2, 1, and 0 were 1.08 (95%CI: 1.03-1.13), 1.16 (95%CI: 1.10-1.23), and 1.19 (95%CI: 1.03-1.37), respectively. Conclusion: In China, adults with insomnia symptoms or short sleep duration have increased risk for kidney stone.

A Prospective Pooled Analysis of Meat Mutagens and Colorectal Adenoma and Cancer in the US and EPIC Studies: Findings with an Emphasis on Improving Exposure Measurements.

In animal studies, heterocyclic amines (HCAs) are recognized as having strong carcinogenicity, therefore we have hypothesized that HCAs might be associated with the risk of colorectal adenoma (CRA) and cancer (CRC). We used the Keywords of "Heterocyclic amines and colorectal cancer" to search, there were showing published articles (n=200). After reviews of titles, abstracts, and full articles, seven prospective cohort studies were included in the pooled analysis. Exposures to HCAs 2-amino-3,8-dimethylimidazo(4,5-j)quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo(4,5-f)quinoxaline (DiMeIQx), meat-derived mutagenicity (MDM), and the risk of CRA and CRC were examined. The estimated HCA intake as ng/day and ng/1,000 kcal/day by participants and by studies were examined. The ln(HR) and se(ln(HR)) were estimated from the multivariable-adjusted HR, 95%CI derived from seven published prospective studies in the US and EPIC. The random pooled multivariable-adjusted HR, 95%CI was analyzed using ln(HR) and se(ln(HR)) by STATA-10. For CRC and HCA intake, the null association was observed for MDM, the random pooled multivariable-adjusted HR, (95%CI): 1.11, (1.00, 1.23); for PhIP: 1.00, (0.91, 1.09); and for DiMeIQx: 1.03, (0.87, 1.22). A significant positive association was seen for MeIQx, the random pooled multivariable-adjusted HR, (95%CI):1.12, (1.03, 1.22). For CRA and HCA intake, the null association was observed for MDM, randomly pooled multivariable-adjusted HR, (95%CI): 1.15, (0.99, 1.34), and for DiMeIQx: 1.09, (0.97, 1.23). A significant positive association was seen for PhIP, the random pooled multivariable-adjusted HR, (95%CI): 1.19, (1.02, 1.39), and for MeIQx: 1.17, (1.01, 1.35). The major instances of HCAs were contributed by chicken (54%-74%) for PhIP and by red meat (83%-92%) for MeIQx. However, the estimated PhIP intake (ng/1,000 kcal/day) was remarkably different between studies. We observed a positive association between exposures to MeIQx and the risk of both CRC and CRA which supports the hypothesis of the role of HCAs in developing CRA and CRC. Improving the quality of the estimated HCA intake would be highly concerned for further investigation.

Association of Healthy Lifestyles With Risk of Alzheimer Disease and Related Dementias in Low-Income Black and White Americans.

Although the importance of healthy lifestyles for preventing Alzheimer disease and related dementias (ADRD) has been recognized, epidemiologic evidence remains limited for non-White or low-income individuals who bear disproportionate burdens of ADRD. This population-based cohort study aims to investigate associations of lifestyle factors, individually and together, with the risk of ADRD among socioeconomically disadvantaged Americans. In the Southern Community Cohort Study, comprising two-thirds self-reported Black and primarily low-income Americans, we identified incident ADRD using claims data among participants enrolled in Medicare for at least 12 consecutive months after age 65 years. Five lifestyle factors-tobacco smoking, alcohol consumption, leisure-time physical activity (LTPA), sleep hours, and diet quality-were each scored 0 (unhealthy), 1 (intermediate), or 2 (healthy) based on the health guidelines. A composite lifestyle score was created by summing all scores. Cox regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD, treating death as a competing risk. We identified 1,694 patients with newly diagnosed ADRD among 17,209 participants during a median follow-up of 4.0 years in claims data; the mean age at ADRD diagnosis was 74.0 years. Healthy lifestyles were individually associated with an 11%-25% reduced risk of ADRD: multivariable-adjusted HR (95% CI) was 0.87 (0.76-0.99) for never vs current smoking, 0.81 (0.72-0.92) for low-to-moderate vs no alcohol consumption, 0.89 (0.77-1.03) for ≥150 minutes of moderate or ≥75 minutes of vigorous LTPA each week vs none, 0.75 (0.64-0.87) for 7-9 hours vs >9 hours of sleep, and 0.85 (0.75-0.96) for the highest vs lowest tertiles of the Healthy Eating Index. The composite lifestyle score showed a dose-response association with up to 36% reduced risk of ADRD: multivariable-adjusted HRs (95% CIs) across quartiles were 1 (ref), 0.88 (0.77-0.99), 0.79 (0.70-0.90), and 0.64 (0.55-0.74); p trend <0.001. The beneficial associations were observed regardless of participants' sociodemographics (e.g., race, education, and income) and health conditions (e.g., history of cardiometabolic diseases and depression). Our findings support significant benefits of healthy lifestyles for ADRD prevention among socioeconomically disadvantaged Americans, suggesting that promoting healthy lifestyles and reducing barriers to lifestyle changes are crucial to tackling the growing burden and disparities posed by ADRD.

Triglyceride-Glucose Index Predicts Cardiovascular Outcome in Metabolically Unhealthy Obese Population: A Nationwide Population-Based Cohort Study.

BackgroundThis study assesses the prognostic value of the triglyceride–glucose (TyG) index for cardiovascular (CV) risk in subgroups based on metabolic health and obesity status.MethodsOriginally, 514,866 participants were enrolled from the Korean National Health Insurance Service-National Health Screening Cohort. The study participants were categorized into four groups: metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). The TyG index was calculated using the following formula: ln (fasting triglyceride [mg/dL]×fasting plasma glucose [mg/dL]/2). Participants were followed from 2009 to 2015 for CV events and CV mortality according to the TyG index.ResultsAfter exclusions, the final study cohort contained 292,206 people. During the follow-up, 9,138 CV events and 1,163 CV deaths were documented. When the high and low TyG groups were compared, the high TyG group had a substantially increased risk of CV events among the MUNO and MUO participants (multivariable-adjusted hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07–1.30 and 1.27 [1.14–1.42], respectively). In participants with MUO status, CV mortality was also significantly increased in the high TyG group compared with the corresponding low TyG group (multivariable-adjusted HR, 1.48; 95% CI, 1.13–1.93). In contrast, a high TyG index was not related to CV mortality in the MHNO, MHO, and MUNO groups.ConclusionThe predictive value of the TyG index can vary across populations. Among MUO participants, the TyG index was significantly and positively correlated with unfavorable CV outcomes.

The Dietary Branched-Chain Amino Acids Transition and Risk of Type 2 Diabetes Among Chinese Adults From 1997 to 2015: Based on Seven Cross-Sectional Studies and a Prospective Cohort Study.

BackgroundThe situation is grim for the prevention and control of type 2 diabetes (T2D) and prediabetes in China. Serum and dietary branched-chain amino acids (BCAAs) were risk factors for T2D. However, there is a lack of information on trends in consumption of BCAAs and the risk of T2D associated with BCAAs intake, based on nationally representative data in China. Thus, we aimed to comprehensively describe the dietary BCAAs transition and risk of T2D, at a national level among Chinese adults from 1997 to 2015.MethodsThe data sources were the China Health and Nutrition Survey (CHNS) and China Nutrition and Health Survey (CNHS). Cross-sectional data on intake were obtained from CHNS (1997, n = 9,404), CHNS (2000, n = 10,291), CHNS (2004, n = 9,682), CHNS (2006, n = 9,553), CHNS (2009, n = 9,811), CHNS (2011, n = 12,686) and CNHS (2015, n = 71,695). Prospective cohort data were obtained CHNS (1997–2015, n = 15,508).ResultsFrom 1997 to 2015, there was a significant decreasing trend in the BCAAs intake of Chinese adults in all subgroups (P < 0.0001) except for Leu in 80 or older, and a decreasing trend in the consumption of BCAAs after 40 years old (P < 0.05). The mean intake of BCAAs in the population of cohort study was 11.83 ± 3.77g/day. The 95% CI was above the HR of 1.0, when the consumptions were higher than 14.01, 3.75, 6.07, 4.21 g/day in BCAAs, Ile, Leu and Val, based on RCS curves. According to the Cox proportional hazards models, Compared with individuals with BCAAs consumption of 10.65–12.37 g/day, the multivariable-adjusted HR for diabetes was 2.26 (95% CI 1.45 to 3.51) for individuals with consumption of BCAAs more than 18.52 g/day. A statistically significant positive association between BCAAs intake and risk of T2D was observed in males or participants aged 45 years and older, but not in females or participants younger than 45 years.ConclusionOur results reveal a trend toward decreased BCAAs intake in Chinese from 1997 to 2015. After 40 years of age, consumption of BCAAs declined with increasing age. Higher BCAAs intake was associated with higher risk of T2D. This relationship is more stable among men and middle-aged and elderly people.

Macronutrient quality index and cardiovascular disease risk in the Seguimiento Universidad de Navarra (SUN) cohort

PurposeTo assess the association between a multi-dimensional Macronutrient Quality Index (MQI) and the risk of cardiovascular disease (CVD) in a Mediterranean cohort.MethodsProspective analyses among 18,418 participants (mean age 36 years, 60.8% women) of the Seguimiento Universidad de Navarra (SUN) cohort. Dietary intake information was obtained through a validated semi-quantitative food-frequency questionnaire (FFQ). The MQI (expressing high-quality macronutrient intake) was calculated based on three previously reported quality indices: the Carbohydrate Quality Index (CQI), the Fat Quality Index (FQI), and the Healthy Plate Protein source Quality Index (HPPQI). Adherence to the Mediterranean diet (MedDiet) and Provegetarian Diet was evaluated using the Trichopoulou index and the score proposed by Martínez-González, respectively. CVD was defined as new-onset stroke, myocardial infarction, or CVD death.ResultsAfter a median follow-up time of 14 years (211,744 person-years), 171 cases of CVD were identified. A significant inverse association was found between the MQI and CVD risk with multivariable-adjusted HR for the highest vs. the lowest quartile of 0.60 (95% IC, 0.38–0.96; Ptrend = 0.024).ConclusionIn this Mediterranean cohort, we found a significant inverse relationship between a multidimensional MQI (expressing high-quality macronutrient intake) and a lower risk of CVD.

Physical activity and/or sedentary behaviour and the development of functional disability in community-dwelling older adults in Tsuru, Japan: a prospective cohort study (the Tsuru Longitudinal Study)

ObjectivesTo clarify the association between moderate-to-vigorous physical activity (MVPA) and/or sedentary behaviour (SB) and the incidence of functional disability (FD) in older adults.DesignProspective cohort study.SettingLocal municipality of Tsuru, Yamanashi, Japan....

Self-reported sleep characteristics and risk for incident vertebral and hip fracture in women

ObjectiveTo examine the relationships between self-reported sleep characteristics and risk of incident vertebral fracture and hip fracture in women. DesignLongitudinal cohort study. SettingNurses’ Health Studies (NHS: 2002-2014, NHSII: 2001-2015). ParticipantsTotal 122,254 female registered nurses (46,129 NHS, 76,125 NHSII) without prior history of fracture. ExposureSleep was characterized by 4 sleep-related domains—sleep duration, sleep difficulty, snoring, and excessive daytime sleepiness—assessed by self-reported questionnaires. OutcomesSelf-reports of vertebral fracture were confirmed by medical record review and hip fracture was assessed by biennial questionnaires. ResultsOver 12-14 years of follow-up, 569 incident vertebral fracture cases (408 in NHS, 161 in NHSII) and 1,881 hip fracture cases (1,490 in NHS, 391 in NHSII) were documented. In the pooled analysis, the multivariable-adjusted HR (95% CI) for vertebral fracture was 1.20 (0.86, 1.66) for sleep duration ≤5 hours vs. 7 hours and 0.82 (0.60, 1.12) for ≥9 vs. 7 hours; 1.63 (0.93, 2.87) for sleep difficulties all-the-time vs. none/little-of-the-time (p-trend = 0.005); 1.47 (1.05, 2.05) for snoring every night/week vs. never/occasionally (p-trend = 0.03), and 2.20 (1.49, 3.25) for excessive daytime sleepiness daily vs. never (p-trend < 0.001). In contrast, associations were not observed with hip fracture risk. ConclusionPoorer sleep characteristics were associated with risk of vertebral fracture. Our study highlights the importance of multiple dimensions of sleep in the development of vertebral fractures. Further research is warranted to understand the role of sleep in bone health that may differ by fracture site, as well as sleep interventions that may reduce the risk of fracture.

Calcaneal quantitative ultrasound is associated with all-cause and cardiovascular disease mortality independent of hip bone mineral density

SummaryOsteoporosis has been linked with increased risk of cardiovascular disease previously. However, few studies have detailed bone and vascular information. In a prospective study of older women, we demonstrated heel quantitative ultrasound measures were associated with increased cardiovascular and all-cause mortality, independent of established cardiovascular risk factors.IntroductionOsteoporosis and low bone mineral density (BMD) have been previously linked to cardiovascular disease (CVD) and mortality. Calcaneal quantitative ultrasound (QUS) is used to evaluate bone material properties, especially in older women. However, it is uncertain whether it is related to risk of mortality. This study was aimed to investigate the association between calcaneal QUS measurements and 15-year all-cause and CVD mortality in 1404 older women (mean age 75.2 ± 2.7 years).MethodsOne thousand four hundred four older women, participants of Calcium Intake Fracture Outcome study (CAIFOS), had calcaneal bone measured at baseline (1998) and followed for 15 years. The primary outcomes, any deaths, and deaths attributable to cardiovascular causes ascertained by using linked data were obtained from Western Australia data linkage system.ResultsOver the 15 years of follow-up (17,955 person years), 584 of the women died, and 223 from CVD. For every standard deviation (SD), reduction in broadband ultrasound attenuation (BUA) in minimally and multivariable-adjusted model including cardiovascular risk factors increased relative hazards for all-cause (multivariable-adjusted HR 1.15; 95%CI: 1.06–1.26, p = 0.001) and CVD mortality (multivariable-adjusted HR 1.20; 95%CI: 1.04–1.38, p = 0.010). Such relationships also persisted when hip BMD was included in the model (all-cause mortality HR 1.19; 95%CI: 1.07–1.33, p = 0.002; CVD mortality HR 1.28; 95%CI: 1.07–1.53, p = 0.008).ConclusionBUA is associated with all-cause and CVD mortality in older women independent of BMD and established CVD risk factors. Understanding why and how these are related may provide further insights about the bone-vascular nexus as well as therapeutic targets benefiting both systems.

Associations of body mass index and waist circumference with hospitalization risk of kidney stones in Chinese adults

Objective: To evaluate the associations of body mass index (BMI) and waist circumference with hospitalization risk of kidney stones in Chinese adults. Methods: This study used long-term follow-up data from China Kadoorie Biobank. After excluding participants with chronic kidney disease, cancer, and extreme BMI or waist circumference values at baseline, 502 096 participants were included in the present analysis. Cox proportional hazards regression models were used to estimate the associations of BMI and waist circumference with hospitalization risk of kidney stones. Results: During an average follow-up period of (10.7±2.2) years, 12 396 participants were hospitalized for the first time with kidney stones. Using the participants with BMI (kg/m2) of 20.5-22.4 as reference, the multivariable-adjusted HR (95%CI) for those with BMI of <18.5, 18.5-20.4, 22.5-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and ≥30.0 were 0.96 (0.87-1.05), 0.94 (0.88-1.00), 1.11 (1.05-1.17), 1.25 (1.18-1.32), 1.29 (1.21-1.37), 1.39 (1.28-1.50), and 1.54 (1.40-1.71), respectively. For every 1 kg/m2 increase in BMI, the HR of kidney stones hospitalization increased by 4% (HR=1.04, 95%CI: 1.04-1.05). Using the participants with waist circumference (cm) of 75.0-79.9 as reference, the multivariable-adjusted HR (95%CI) for those with waist circumference of <65.0, 65.0-69.9, 70.0-74.9, 80.0-84.9, 85.0-89.9, 90.0-94.9, and ≥95.0 were 0.82 (0.74-0.91), 0.85 (0.80-0.92), 0.95 (0.89-1.00), 1.16 (1.09-1.22), 1.22 (1.15-1.30), 1.28 (1.19-1.38), and 1.46 (1.35-1.58), respectively. For every 5 cm increase in waist circumference, the HR of kidney stones hospitalization increased by 9% (HR=1.09, 95%CI: 1.08-1.10). After mutually adjusting for BMI and waist circumference in the above models, the association between BMI and hospitalization risk of kidney stones disappeared. In contrast, the association between waist circumference and hospitalization risk of kidney stones remained unchanged. Conclusions: BMI and waist circumference were positively associated with hospitalization risk of kidney stones. The increased waist circumference was an independent risk factor for kidney stones among Chinese adults.

Cardiorespiratory Fitness, Inflammation, and Risk of Chronic Obstructive Pulmonary Disease in Middle-Aged Men: A COHORT STUDY.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic lung inflammation. The relationship between cardiorespiratory fitness (CRF) and COPD has not been well characterized. We aimed to evaluate the independent and joint associations of inflammation (high-sensitivity C-reactive protein [hsCRP]) and CRF with COPD risk in a cohort of White men. Among 2274 men aged 42-61 yr at baseline, serum hsCRP level was measured using an immunometric assay and CRF was assessed using a respiratory gas exchange analyzer. The level of hsCRP was categorized as normal and high (≤3 and >3 mg/L, respectively) and CRF as low and high. We corrected for within-person variability in exposures using repeat measurements taken several years apart. A total of 116 COPD cases occurred during a median follow-up of 26.0 yr. The age-adjusted regression dilution ratio of hsCRP and CRF was 0.57 (95% CI, 0.50-0.64) and 0.58 (95% CI, 0.53-0.64), respectively. Comparing high versus normal hsCRP levels, the multivariable-adjusted HR for COPD was 1.79 (95% CI, 1.20-2.68). The COPD risk decreased linearly with increasing CRF. The multivariable-adjusted HR for COPD per 1-SD increase in CRF was 0.75 (95% CI, 0.60-0.95). Compared with men with normal hsCRP-low CRF, high hsCRP-low CRF was associated with an increased COPD risk, 1.80 (95% CI, 1.12-2.89), with no evidence of an association for high hsCRP-high CRF and COPD risk, 1.35 (95% CI, 0.68-2.69). Both hsCRP and CRF are associated with COPD risk in middle-aged men. However, high CRF levels attenuate the increased COPD risk related to high hsCRP levels.

Association of education levels with the risk of hypertension and hypertension control: a nationwide cohort study in Chinese adults

BackgroundEducation attainment can improve life expectancy and guide healthy behaviours throughout an entire lifetime. A nationwide longitudinal study of the association of education status with the risk of hypertension and...

Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults

BackgroundOlive oil consumption has been shown to lower cardiovascular disease risk, but its associations with total and cause-specific mortality are unclear. ObjectivesThe purpose of this study was to evaluate whether olive oil intake is associated with total and cause-specific mortality in 2 prospective cohorts of U.S. men and women. MethodsThe authors used multivariable-adjusted Cox proportional-hazards models to estimate HRs for total and cause-specific mortality among 60,582 women (Nurses’ Health Study, 1990-2018) and 31,801 men (Health Professionals Follow-up Study, 1990-2018) who were free of cardiovascular disease or cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years. ResultsDuring 28 years of follow-up, 36,856 deaths occurred. The multivariable-adjusted pooled HR for all-cause mortality among participants who had the highest consumption of olive oil (>0.5 tablespoon/day or >7 g/d) was 0.81 (95% CI: 0.78-0.84) compared with those who never or rarely consumed olive oil. Higher olive oil intake was associated with 19% lower risk of cardiovascular disease mortality (HR: 0.81; 95% CI: 0.75-0.87), 17% lower risk of cancer mortality (HR: 0.83; 95% CI: 0.78-0.89), 29% lower risk of neurodegenerative disease mortality (HR: 0.71; 95% CI: 0.64-0.78), and 18% lower risk of respiratory disease mortality (HR: 0.82; 95% CI: 0.72-0.93). In substitution analyses, replacing 10 g/d of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil was associated with 8%-34% lower risk of total and cause-specific mortality. No significant associations were observed when olive oil was compared with other vegetable oils combined. ConclusionsHigher olive oil intake was associated with lower risk of total and cause-specific mortality. Replacing margarine, butter, mayonnaise, and dairy fat with olive oil was associated with lower risk of mortality.

Abstract 10151: Association of Polygenic Risk Scores for Pre-Eclampsia and Blood Pressure with Hypertensive Pregnancy Disorders

Introduction: Blood pressure (BP) is a known risk factor for pre-eclampsia. We examined whether a BP-polygenic risk score (PRS) as compared with a pre-eclampsia-PRS, could also predict gestational hypertension (GHT), pre-eclampsia, and eclampsia. Methods: Our study sample included 116434 genotyped, previously-pregnant participants of the FinnGen cohort who were followed up between 1969-2019. PRSs for systolic BP and pre-eclampsia were derived using UK Biobank summary statistics for &gt;1.1 million single nucleotide polymorphisms. Results: We observed 6561 cases of GHT, 5263 cases of pre-eclampsia, and 385 cases of eclampsia. As shown in the Figure, we observed that the BP-PRS was associated with GHT (multivariable-adjusted HR for 1-SD increase in PRS, 1.40; 95% CI, 1.36-1.43; p=9x10 -160 ), pre-eclampsia (HR, 1.26 (95% CI 1.23-1.30, p=1.6x10 -63 ) and with eclampsia (HR, 1.29 (95% CI, 1.16-1.42, p=8.1x10 -7 ), respectively. The pre-eclampsia-PRS was also associated with GHT (HR, 1.09; 95% CI 1.07-1.12, p=1.0x10 -12 ) pre-eclampsia (HR, 1.09; 95% CI, 1.06-1.12, p=2.2x10 -10 ) and eclampsia (HR, 1.12, 95% CI, 1.02-1.24, p=0.023), although these associations were more modest. The model c-statistic for incident pre-eclampsia increased from 0.544 to 0.591 (95% CI for difference, 0.022-0.034, p&lt;1x10 -300 ) when BP-PRS was included in a model with pre-eclampsia-PRS. Conclusions: Our study confirms that the increased risks for developing GHT, pre-eclampsia and eclampsia are strongly associated with genetic factors related to BP. A BP-PRS seems to be an even stronger predictor of hypertensive pregnancy complications than a pre-eclampsia-PRS. Our results suggest common pathways for the development of these diseases that need to be further investigated.

Post-Treatment FDG-PET/CT Hopkins Criteria Predict Locoregional Recurrence After Definitive Radiotherapy for Oropharyngeal Squamous Cell Carcinoma

Surveillance after definitive radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is critical to confirm clinical complete response, as a subset of patients develop locoregional recurrences (LRR). The Hopkins Criteria are a standardized qualitative system for assessing response using post-treatment PET/CT and are validated for overall (OS) and progression-free survival (PFS). We hypothesized that the Hopkins Criteria score is independently prognostic for LRR.We conducted an institutional retrospective study of adult patients with newly-diagnosed node-positive non-metastatic OPSCC treated with definitive (chemo)radiotherapy. Patients were eligible if they completed a pre- and post-radiotherapy PET/CT within 24 weeks after treatment. The primary outcome was the cumulative incidence of locoregional recurrence/persistence. A single board-certified nuclear medicine physician assigned Hopkins scores, which were considered either positive (scores 4-5) or negative (scores 1-3).Between 2004-2018, 259 patients were included in this analysis, while an additional 221 were excluded, most commonly due to lack of post-treatment PET/CT [37%] or N0 disease [22%]. Most patients were men (90%), 47% had never smoked, 86% had p16+/HPV+ tumors, and 39% had T3-4 tumors. Nearly all (98%) received concurrent chemotherapy, while 11% received induction chemotherapy. Median clinical follow-up was 40 months. Following radiotherapy, the first post-treatment PET/CT was positive (score 4-5) at the primary site in 32 patients (12%), cervical lymph nodes in 26 patients (10%), and either the primary site or neck in 50 patients (19%). This PET/CT was performed at a median of 3.3 months [range, 1.6-6.0] after radiotherapy. Thirty-four (13%) LRRs were observed. The sensitivity, specificity, negative predictive value, and overall accuracy of the Hopkins score for LRR were 68%, 88%, 95%, and 85%. The 36-month cumulative incidence of LRR was greater among patients with Hopkins scores 4-5 (45% vs. 5%, multivariable-adjusted HR 14.16, P < 0.001). Positive scores were similarly prognostic for 36-month OS (69% vs. 94%) and PFS (55% vs. 87%). LRR was similar among patients with scores of 3 relative to scores of 1-2. Performance was reduced when PET/CTs were obtained within 2.5 months of radiotherapy (accuracy: ≤2.5 months: 73%; 2.5-3.5 months: 85%; 3.5-6.0 months: 87%). Twenty-two negative biopsies or surgeries were performed among patients without LRR; negative biopsies/surgeries were more common after early PET/CT (≤2.5 months: 36%; 2.5-3.5 months: 9%; 3.5-6.0 months: 9%, P = 0.03).There is a lack of consensus reporting standards for response assessment after definitive radiotherapy for OPSCC. The Hopkins Criteria are an easily-implemented standard that appear to offer high accuracy for recurrence and death. These data support an initial PET/CT at least three months after radiotherapy to limit unnecessary diagnostic procedures.

Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization: A Cohort Study.

Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10-20mg or rosuvastatin 5-10mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40-80mg or rosuvastatin 20mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. At 12months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86-1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74-1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.

Simple sugar intake and cancer incidence, cancer mortality and all-cause mortality: A cohort study from the PREDIMED trial

To examine associations between intake of simple sugars and cancer incidence, cancer mortality, and total mortality in a prospective cohort study based on the PREDIMED trial conducted from 2003 to 2010. Participants were older individuals at high cardiovascular risk. Exposures were total sugar, glucose and fructose from solid or liquid sources, and fructose from fruit and 100% fruit juice. Cancer incidence was the primary outcome; cancer mortality and all-cause mortality were secondary outcomes. Multivariable-adjusted, time-dependent Cox proportional hazard models were used. Of 7447 individuals enrolled, 7056 (94.7%) were included (57.6% women, aged 67.0±6.2 years). 534 incident cancers with 152 cancer deaths and 409 all-cause deaths were recorded after a median follow-up of 6 years. Intake of simple sugars in solid form was unrelated to outcomes. Higher cancer incidence was found per 5g/day increase in intake of liquid sugars, with multivariable-adjusted HR of 1.08 (95% CI, 1.03-1.13) for total liquid sugar, 1.19 (95% CI, 1.07-1.31) for liquid glucose, 1.14 (95% CI, 1.05-1.23) for liquid fructose, and 1.39 (95% CI, 1.10-1.74) for fructose from fruit juice. Cancer and all-cause mortality increased to a similar extent with intake of all sugars in liquid form. In categorical models, cancer risk was dose-related for all liquid sugars. Simple sugar intake in drinks and fruit juice was associated with an increased risk of overall cancer incidence and mortality and all-cause mortality. This suggests that sugary beverages are a modifiable risk factor for cancer and all-cause mortality.

Association of depressive symptoms and risk of knee pain: the moderating effect of sex

BackgroundDepression has been shown in some studies to be associated with knee pain. Females were widely recognized as more vulnerable to depression and knee pain than males. However, the role of sex in this correlation was under-researched. This study aimed to investigate the association between depressive symptoms and subsequent knee pain, as well as whether and how sex would moderate this association based on a four-wave (Wave 1 in 2010–2011, Wave 2 in 2013, Wave 3 in 2015, and Wave 4 in 2018) longitudinal study among middle-aged and elderly Chinese adults.MethodsSeventeen thousand seven hundred eight participants were recruited and followed in the China Health and Retirement Longitudinal Study (CHARLS). Ten thousand four hundred fifty-one entered the final analysis based on the inclusion and exclusion criteria. Knee pain was assessed by self-report. Depressive symptoms were evaluated using the validated 10-item Center for Epidemiological Studies-Depression Scale (CESD-10). Cox proportional hazards models were used to calculate hazard ratios with 95% confidence intervals (CIs) after controlling potential confounders to examine the association between depressive symptoms and subsequent incident and persistent knee pain. Non-linear association of depressive symptoms score (CESD-10) and risk of knee pain was also investigated via applying 3-knotted restricted cubic spline regression. An interaction term of depressive symptoms status and sex was added to investigate the moderating effect of sex on the relationship between depressive symptoms status and the risk of knee pain.ResultsThe median follow-up time was seven years for all the outcomes. Participants with depressive symptoms were 1.45 times (95% CI: 1.34–1.56) and 2.16 times (95% CI: 1.85–2.52) more likely to develop the incident and persistent knee pain after multivariable were adjusted, compared with those without depressive symptoms. There was a non-linear association between CESD-10 score and risk of knee pain. Compared with females, males had an enhanced correlation between depressive symptoms status and knee pain (multivariable-adjusted HR: 1.22, 95% CI: 1.05–1.42 and HR: 1.57, 95% CI: 1.14–2.17 for the incident and persistent knee pain, respectively).ConclusionDepressive symptoms are independently associated with an excess risk of knee pain, with a stronger correlation for males than females among middle-aged and elderly Chinese adults.

Abstract 2909: Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients

Abstract Background: The intestinal microbiome is intimately involved in the pathogenesis of colorectal cancer and likely holds further insights to improve the treatment and management of this deadly disease. In a clinical cohort of patients with colon and rectal cancers, we characterized the tumor microbiota of surgical specimens and evaluated associations with prognostic factors, consensus molecular subtypes (CMS), and survival. Methods: In 167 patients diagnosed with stage II through IV colon and/or rectal cancer who underwent evaluation and surgical resection (no prior systemic therapy) at The University of Texas MD Anderson Cancer, we characterized the tumor microbiome via 16S rRNA gene sequencing. Each patient's tumor was classified via CMS, a gene expression-based colorectal cancer classification system; and all patients were prospectively followed for disease progression, recurrence, or death. Microbiota diversity and composition were assessed with regard to clinicopathologic and tumor features; and associations with survival were further evaluated in multivariable Cox proportional hazards models. Results: Left- vs. right-sided colon tumors were characterized by higher microbial diversity, distinct community features, and increased abundance of Bacteroides and Fusobacterium. CMS1 (microsatellite instability immune) vs. CMS2 (canonical) tumors were characterized by higher Bacteroides and Fusobacterium and lower Escherichia (all P&amp;lt;0.05). Fusobacterium-positive and Escherichia-positive tumors were associated with improved 5-year overall survival [presence vs. absence, multivariable-adjusted HR and 95% CI: 0.43 (0.20-0.93) and 0.32 (0.19-0.78), respectively]. Bacteroides was enriched among stage II/III patients who progressed within 2-years (log-rank p&amp;lt;0.001). Conclusions: Our findings are consistent with those of other groups suggesting the landscape of the tumor microbiome differs by sidedness and molecular subtype, holding important clues and exploitable targets to improve outcomes in colorectal cancer patients. Citation Format: Fangyu Li, Michael G. White, Jennifer Davis, Kristi L. Hoffman, David Menter, Nadim Ajami, Xiaotao Zhang, Jeffrey S. Morris, Robert R. Jenq, Joseph Petrosino, Jennifer A. Wargo, Scott Kopetz, Carrie R. Daniel. Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2909.