Predicted 25-hydroxyvitamin D over the adult life and the risk of ovarian cancer.

The evidence from previous studies of serum 25-hydroxyvitamin D [25(OH)D] and ovarian cancer risk are not conclusive. However, 25(OH)D was generally only measured in late adulthood, which may not capture the etiologically relevant exposure periods. We investigated predicted 25(OH)D over the adult lifetime in relation to ovarian cancer risk in a population-based case-control study conducted from 2011 to 2016 in Montreal, Canada (490 cases, 896 controls). Predicted 25(OH)D was computed using previously validated regression models. Unconditional multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for average predicted 25(OH)D over the adult life and risk. In addition, the relative importance of different periods of past 25(OH)D exposure was explored using a weighted cumulative exposure (WCE) model. For each 20 nmol/L increase in average predicted 25(OH)D over the adult life, the aOR (95% CI) was 0.73 (0.55-0.96). In WCE analyses, the inverse association was strongest for exposures 5 to 20 years and 35 to 55 years prior to diagnosis, with aORs (95% CIs) of 0.82 (0.69-0.94) and 0.79 (0.66-1.02), respectively, for each 20 nmol/L increase in predicted 25(OH)D. These results support an inverse association between 25(OH)D in adulthood and ovarian cancer risk.

Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.

The association of cumulative low-density lipoprotein cholesterol exposure and carotid intima-media thickness in a young adulthood population.

OBJECTIVE: To investigate the association between cumulative exposure to low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (IMT) in the young adulthood population. METHODS: Young adult subject (18-45 year old) from the Kailuan Study group who participated in the same period of follow-up and received carotid artery ultrasound were selected as the observation subjects. Among them, 3651 cases met the inclusion criteria, which required that carotid artery color ultrasound examinations be completed from 2010 to 2016, with complete IMT measurements, LDL-C data collected at least twice before carotid ultrasound, and participants' age to be ≤ 45 years at the time of carotid artery color ultrasound examination. Linear regression was used to analyze the correlation between time-weighted average (TWA) to LDL-C cumulative exposure and IMT the young population. Logistic regression was used to analyze the effects of different TWA groups on IMT thickening. Considering that the use of anti hypertensive drugs and lipid-lowering drugs may affect TWA LDL-C, this study excluded people taking antihypertensive drugs and lipid-lowering drugs, and conducted a repeat analysis of the main results. RESULTS: There was a positive correlation between TWA LDL-C and IMT, with IMT increasing by 0.017 mm when TWA LDL-C increased by 1 mmol/L * year. The TWA LDL-C in the highest group was identified as a risk factor for IMT thickening, with odds ratio (OR) values of 1.812(1.027 ~ 3.200) in the T3 group. After excluding patients taking antihypertensive drugs and lipid-lowering drugs, the results still showed that the T3 group with the highest TWA LDL-C was a risk factor for IMT thickening, with an OR value of 1.850(0.988-3.464), P for trend is 0.043. CONCLUSION: This cohort study revealed that TWA LDL-C is positively correlated with IMT in young adulthood for risk stratification, and control LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic disease. TRIAL REGISTRATION: ChiCTR-TNC-11001489.

The weighted cumulative exposure method and its application to pharmacoepidemiology: A narrative review.

PURPOSE: The weighted cumulative exposure (WCE) method has been used in a number of fields including pharmacoepidemiology where it can account for intensity, duration and timing of exposures on the risk of an outcome. The method uses a data driven approach with flexible cubic B-splines to assign weights to past doses and select an aetiologically appropriate time window. Predictions of risk are possible for common exposure patterns encountered in real-world studies. The purpose of this study was to describe applications of the WCE method to pharmacoepidemiology and assess the strengths and limitations of the method. METHOD: A literature search was undertaken to find studies applying the WCE method to the study of medicines. Articles published in PubMed using the search term 'weighted cumulative exposure' and articles citing Sylvestre et al. (2009) in Google Scholar or Scopus up to March 2023 were subsequently reviewed. Articles were selected based on title and review of abstracts. RESULTS: Seventeen clinical applications using the data-driven WCE method with flexible cubic splines were identified in the review. These included 3 case-control studies and 14 cohort studies, of which 12 were analysed with Cox proportional hazards models and 2 with logistic regression. Thirteen studies used time windows of 1 year or longer. Of 11 studies which compared conventional models with the WCE method, 10 (91%) studies found a better fit with WCE models while one had an equivalent fit. The freely available 'WCE' software package has facilitated the applications of the WCE method with flexible cubic splines. CONCLUSIONS: The WCE method allows additional insights into the effect of cumulative exposure on outcomes, including the timing and intensity (dose) of the exposure on the risk. The flexibility of the method is particularly well suited to studies with long-term exposures that vary over time or where the current risk of an event is affected by how far the exposure is in the past, which is difficult to model with conventional definitions of exposure. Interpretation of the results can be more complex than for conventional models and would be facilitated by a standardised reporting framework.

The effect of cumulative lipid accumulation product and related long-term change on incident stroke: The Kailuan Study.

BACKGROUND AND AIMS: A single measurement lipid accumulation product (LAP) level has been shown to increase cardiovascular disease, but cumulative LAP on stroke effects is uncertain. METHODS AND RESULTS: This study included 43,089 participants, free of any cardiovascular diseases at baseline, from the Kailuan Study. The cumulative LAP was determined by multiplying the average LAP index and the time interval between two consecutive examinations, resulting in their categorization into four quartile groups. The higher LAP exposure was defined as participants with LAP values exceeding 90% of this population during each health survey. The association between cumulative LAP and stroke was assessed using multivariable Cox proportional hazard models. During a median follow-up period of 11.0 (10.6-11.3) years, 2461 participants developed stroke (of which 2220 were ischemic stroke, 320 were hemorrhagic stroke, and 79 were concurrent). After adjusting for potential confounders, the risk of stroke gradually increased in Groups Q2 to Q4 compared to Q1, with hazard ratios (HRs) ranging from 1.19 (95% CI: 1.05-1.36) to 1.50 (95% CI: 1.30-1.70). Specifically, the risk of ischemic stroke showed an increase from 1.21 (1.06-1.39) to 1.56 (1.36-1.79), while no statistically significant effect was observed for hemorrhagic stroke. The longer duration of higher LAP index exposure was also associated with increased stroke risk. Similar results were obtained in the stratification and sensitivity analyses. CONCLUSION: Cumulative LAP was positively and significantly associated with incident stroke, especially ischemic stroke, and a longer duration of exposure to higher LAP may increase the risk of stroke.

The joint effect of cumulative doses for outdoor air pollutants exposure in early life on asthma and wheezing among young children.

BACKGROUND: Constrained by no proper way to assess cumulative exposure, the joint effect of air pollution cumulative exposure doses on childhood asthma and wheezing (AW) was not understood. OBJECTIVE: To assess the association between cumulative exposure to multiple air pollutants in early life and childhood AW. METHODS: We designed a nested case-control study based on the birth cohort in Jinan City. Children with AW followed up within 2 years after birth were treated as cases, and non-cases in this cohort were treated as the control source population, and the propensity score matching method was used to match each case to 5 controls. We calculated the individual cumulative outdoor exposure doses for each period using an inverse distance weighted model, alongside the complex Simpson's formula, accounting for outdoor time and respiratory volume. The Least absolute shrinkage and selection operator (Lasso) regression was performed to screen for covariates. To analyze the joint effects of pollutants, we employed the weighted quantile sum (WQS) regression model in conjunction with conditional logistic regression. RESULTS: 84 cases and 420 controls were included in this study. The odds ratio (OR) with 95% confidence interval (CI) of the impact of cumulative exposure (mg/m3) after birth on childhood AW was 1.78 (1.15-2.74) for SO2, 1.69 (1.11-2.57) for NO2, and 1.65 (1.09-2.52) for PM2.5, respectively. Furthermore, with each 25th percentile increase in the WQS index, the overall risk of cumulative doses for six pollutants exposure after birth on AW increased by an adjusted OR of 1.10 (1.03, 1.18), and SO2, PM2.5, and NO2 contributed the most to the WQS index. However, no statistically significant association was found between cumulative exposure to all pollutants before birth and childhood AW. CONCLUSIONS: There was a joint effect of the cumulative exposure dose of outdoor air pollutants after birth on AW in children aged 0-2 years. And traffic-related pollutants (SO2, PM2.5, and NO2) make a greater contribution to the joint effect.

Not only baseline but cumulative exposure of remnant cholesterol predicts the development of nonalcoholic fatty liver disease: a cohort study.

BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION: Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.

Aging Intensity for Step-Stress Accelerated Life Testing Experiments.

The aging intensity (AI), defined as the ratio of the instantaneous hazard rate and a baseline hazard rate, is a useful tool for the describing reliability properties of a random variable corresponding to a lifetime. In this work, the concept of AI is introduced in step-stress accelerated life testing (SSALT) experiments, providing new insights to the model and enabling the further clarification of the differences between the two commonly employed cumulative exposure (CE) and tampered failure rate (TFR) models. New AI-based estimators for the parameters of a SSALT model are proposed and compared to the MLEs in terms of examples and a simulation study.

Relationship between the cumulative exposure to atherogenic index of plasma and ischemic stroke: a retrospective cohort study.

BACKGROUND: Atherogenic index of plasma (AIP) has been demonstrated as a surrogate marker for ischemic stroke, but there is limited evidence for the effect of long-term elevation of AIP on ischemic stroke. Therefore, we aimed to characterize the relationship between cumulative exposure to AIP and the risk of ischemic stroke. METHODS: A total of 54,123 participants in the Kailuan Study who attended consecutive health examinations in 2006, 2008, and 2010 and had no history of ischemic stroke or cancer were included. The time-weighted cumulative AIP (cumAIP) was calculated as a weighted sum of the mean AIP values for each time interval and then normalized to the total duration of exposure (2006-2010). Participants were divided into four groups according to quartile of cumAIP: the Q1 group, ≤-0.50; Q2 group, - 0.50 to - 0.12; Q3 group, - 0.12 to 0.28; and Q4 group, ≥ 0.28. Cox proportional hazard models were used to evaluate the relationship between cumAIP and ischemic stroke by calculating hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: After a median follow-up of 11.03 years, a total of 2,742 new ischemic stroke events occurred. The risk of ischemic stroke increased with increasing quartile of cumAIP. After adjustment for potential confounders, Cox regression models showed that participants in the Q2, Q3, and Q4 groups had significantly higher risks of ischemic stroke than those in the Q1 group. The HRs (95% CIs) for ischemic stroke in the Q2, Q3, and Q4 groups were 1.17 (1.03, 1.32), 1.33 (1.18, 1.50), and 1.45 (1.28, 1.64), respectively. The longer duration of high AIP exposure was significantly associated with increased ischemic stroke risk. CONCLUSIONS: High cumulative AIP is associated with a higher risk of ischemic stroke, which implies that the long-term monitoring and maintenance of an appropriate AIP may help prevent such events.

Cumulative exposure to high remnant-cholesterol concentrations increases the risk of cardiovascular disease in patients with hypertension: a prospective cohort study.

BACKGROUND: The relationship of cumulative remnant-cholesterol (Cum-RC) concentration with the risk of cardiovascular disease (CVD) in patients with hypertension remains unclear. METHODS: We studied data for 28,698 individuals for whom three consecutive total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride concentrations were available, and who did not have CVD (14,349 with hypertension and 14,349 without), that was collected between 2006 and 2010. Participants with hypertension were placed into four groups based on Cum-RC quartile: a Q1 group (< 26.40 mg/dl), a Q2 group (26.40-39.56 mg/dl), a Q3 group (39.57-54.65 mg/dl), and a Q4 group (≥ 54.66 mg/dl). Cox proportional hazards models were used to evaluate the relationship between Cum-RC and the risk of CVD. RESULTS: Over a median 10.9 (interquartile range, 10.5-11.3) years, 1,444 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, and compared with the Q1 Cum-RC group of the participants with hypertension, the adjusted hazard ratios for CVD for the Q2-Q4 groups were 1.07(0.92,1.26), 1.08(0.91,1.28), and 1.26(1.03,1.54) (P = 0.0405); those for myocardial infarction were 1.51(1.00,2.31), 2.02(1.22,3.27), and 2.08(1.41,3.28) (P < 0.0001); and those for ischemic stroke were 1.02(0.84,1.24), 1.04(0.86,1.25), and 1.29(1.02,1.62), respectively (P = 0.0336). However, no significant relationship was found between Cum-RC and the risk of hemorrhage stroke. At the same Cum-RC, the risk of CVD was significantly higher in participants with hypertension than in those without. CONCLUSIONS: A consistently high remnant-cholesterol concentration increases the risk of CVD in individuals with hypertension. Therefore, the achievement of blood pressure and RC concentration targets should help reduce the risk of CVD in individuals with hypertension.

Relationship between cumulative exposure to triglyceride-glucose index and heart failure: a prospective cohort study.

BACKGROUND: High triglyceride-glucose index (TyG) is a major risk factor for heart failure, but the long-term effect of high TyG index on the risk of developing heart failure remains unclear. Therefore, we aimed to determine the relationship between the cumulative exposure to TyG index and the risk of heart failure. METHODS: A total of 56,149 participants from the Kailuan Study, who participated in three consecutive health examinations in 2006, 2008, and 2010 and had no history of heart failure or cancer were recruited for this study. The cumulative TyG index was calculated as the weighted sum (value × time) of the mean TyG index for each time interval. The participants were placed into quartiles based on their cumulative TyG index. The study ended on December 31, 2020, and the primary outcome was new-onset heart failure during the follow-up period. In addition, a Cox proportional hazards regression model and a restricted cubic spline analysis were used to further evaluate the relationship between cumulative TyG index and the risk of heart failure. RESULTS: During a median follow-up period of 10.04 years, a total of 1,312 new heart failure events occurred. After adjustment for potential confounding factors, the Cox regression analysis showed that the hazard ratios (95% confidence intervals) for the risk of heart failure in the Q2, Q3, and Q4 groups were 1.02 (0.83,1.25), 1.29 (1.07,1.56) and 1.40 (1.15,1.71), respectively, vs. the Q1 group. The subgroup analysis showed a significant interaction between cumulative TyG index and BMI or waist circumference, but there was no interaction between age, sex and cumulative TyG index. The restricted cubic spline analysis showed a dose-response relationship between cumulative TyG index and the risk of heart failure. In addition, the sensitivity analysis generated results that were consistent with the primary results. CONCLUSIONS: High cumulative TyG index is associated with a higher risk of heart failure. Thus, the TyG index may be useful for the identification of individuals at high risk of heart failure. The present findings emphasize the importance of the long-term monitoring of the TyG index in clinical practice.

Association between cumulative atherogenic index of plasma exposure and risk of myocardial infarction in the general population.

BACKGROUND: Atherogenic index of plasma (AIP) has been confirmed as a novel marker for myocardial infarction (MI), but few evidence on the long-term AIP and MI risk in general populations. We thus aimed to evaluate the relationships of cumulative exposure to AIP and its accumulation time course with the risk of MI. METHODS: A total of 54,440 participants were enrolled in the Kailuan study. Time-weighted cumulative AIP was calculated as the weighted sum of the mean AIP value for each time interval, then normalized by total exposure duration, the exposure duration was from 2006 to 2010. Duration of high AIP exposure was defined as the duration with high AIP and ranged from 0 to 6 years. The time course of AIP accumulation was categorized by the combination of time-weighted cumulative AIP < or ≥ median (- 0.12) and AIP slope. RESULTS: After 11.05 years of follow-up, 766 incident MI cases were documented. After adjustment for potential confounders, higher risk of MI was observed in participants with the highest time-weighted cumulative AIP quartile (HR, 1.89; 95% CI 1.47-2.43), the longest exposure duration of high AIP (HR, 1.52; 95% CI 1.18-1.95), and those with high time-weighted cumulative AIP and negative slope (HR, 1.42; 95% CI 1.13-1.79). CONCLUSIONS: Long-term cumulative exposure to AIP and the time course of AIP accumulation increased the risk of MI. High AIP earlier resulted in a greater risk increase than later in life with the same time-weighted cumulative AIP, emphasizing the importance of controlling atherogenic dyslipidemia early in life.

Effect of cumulative body mass index exposure and long-term related change on incident non-alcoholic fatty liver disease.

BACKGROUND: To evaluate the association between cumulative body mass index (BMI) and long-term BMI change with non-alcoholic fatty liver disease (NAFLD). METHODS: We included 19 477 adult participants (12 556 men and 6921 women) from the Kailuan study from January 2006 to December 2013. Cumulative BMI was assessed using a quadratic mixed-effects method by sex before the index year; then, the NAFLD outcome was followed till December 2019. The long-term BMI change was calculated as the percentage change in average cumulative BMI from the baseline BMI. RESULTS: During a median follow-up of 5.63 years, 6229 individuals developed incident NAFLD. Independent of baseline BMI, the NAFLD risk escalated with the cumulative BMI with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 1.60 (1.48-1.73) and 2.28 (2.06-2.53) for the intermediate tertile and the highest tertile (Ptrend <0.001). The association is amplified in women and the young. Compared to a stable weight (BMI change: -3% to 3%), NAFLD risk increased in the baseline BMI < 24 kg/m2 group with weight gain (BMI change: >3%) and decreased in BMI ≥24 kg/m2 group with weight loss (BMI change: <-3%) for men and women. However, we only observed a decreased NAFLD risk in men (HR: 0.82, 95% CI: 0.69-0.97) with BMI < 24 kg/m2 and weight loss. CONCLUSIONS: Monitoring cumulative BMI may help to identify high-risk NAFLD populations. The association between weight gain or loss varies by sex and baseline BMI, suggesting the importance of individualized weight management for NAFLD prevention.

Integrating Physiologically Based Pharmacokinetic Modeling-Based Forward Dosimetry and in Vitro Bioassays to Improve the Risk Assessment of Organophosphate Esters on Human Health.

The ability to accurately assess the health risks of contaminants is limited by the shortcomings of toxicological standards. Using organophosphate esters (OPEs) as an example, this study attempted to integrate physiologically based pharmacokinetic (PBPK)-based forward dosimetry and in vitro bioassays to assess the likelihood of contaminants inducing biological effects in humans. The total exposure level of OPEs for Chinese residents was 19.5 ± 8.71 ng/kg/day with inhalation being the main exposure pathway. Then, human PBPK models were developed for individual OPEs to predict their steady-state concentrations in human tissues, and the predicted median levels in blood were close to the measurements. The reference doses (RfDs) of OPEs based on in vitro bioassays were comparable to in vivo animal-derived RfDs, demonstrating the reliability of in vitro bioassays. Therefore, the likelihood of OPEs inducing bioactivities in humans (RQin-vitro) was calculated using in vitro toxicity data and OPE levels in human tissues. The RQin-vitros of tris(2-chloroisopropyl) phosphate, tris(1,3-dichloropropyl) phosphate, and triphenyl phosphate (7.68 × 10-5-3.18 × 10-3) were comparable to the risks assessed using traditional RfDs (5.22 × 10-5-1.94 × 10-3), indicating the credibility of the method proposed in this study. This study establishes a new framework to improve the health risk assessment of contaminants without sufficient toxicity data and minimize the need for animal experimentation.

Importance of accounting for timing of time-varying exposures in association studies: Hydrochlorothiazide and non-melanoma skin cancer.

PURPOSE: Hydrochlorothiazide (HCTZ), a widely prescribed antihypertensive drug with photosensitising properties, has been linked with non-melanoma skin cancer (NMSC) risk. However, previous analyses did not fully explore if and how the impact of past HCTZ exposures accumulates with prolonged use and/or depends on time elapsed since exposures. Therefore, we used different models to more comprehensively assess how NMSC risk vary with HCTZ exposure, and explore how the results may depend on modeling strategies. METHODS: We used different parametric models with alternative time-varying exposure metrics, and the flexible weighted cumulative exposure model (WCE) to estimate associations between HCTZ exposures and NMSC risk in a population-based cohort of HCTZ users over 65 years old, in the province of Ontario, Canada. RESULTS: Among 3844 HCTZ users, 273 developed NMSC during up to 8 years of follow-up. In parametric models, based on all exposures, increased duration of past HCTZ use was associated with an increase of NMSC risk but cumulative dose showed no systematic association. Yet, WCE results suggested that only exposures taken 2.5-4 years in the past were associated with the current NMSC hazard. This finding led us to re-define the parametric models, which also confirmed that any HCTZ dose taken outside this time-window were not systematically associated with NMSC incidence. CONCLUSIONS: Our analyses illustrate how flexible modeling may yield new insights into complex temporal relationships between a time-varying drug exposure and risks of adverse events. Duration and recency of antihypertensive agents exposures must be taken into account in evaluating risk and benefits.

Accumulated exposure to high non-high-density lipoprotein cholesterol increases the risk of cardiovascular diseases in hypertensive individuals: An 11-year prospective cohort study.

BACKGROUND: The relationship of cumulative non high-density lipoprotein-cholesterol (Cum-non-HDL-C) concentration with the risk of cardiovascular disease (CVD) in individuals with hypertension remains unclear. METHODS: In total 27 234 participants for whom three consecutive total cholesterol and HDL-C concentrations were available, and who did not have CVD, comprising 13 617 with hypertension and 13 617 without from 2006 to 2010. Participants were placed into four groups according to Cum-non-HDL-C. Cox proportional hazards models were used to evaluate the relationship between Cum-non-HDL-C and the risk of CVD. RESULTS: Over a median 11 years, 1,298 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, compared with participants with hypertension and Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios and 95% confidence intervals of CVD associated with Cum-non-HDL-C values of 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.23 (1.01, 1.34), 1.27 (1.04, 1.56), and 1.51 (1.13, 2.01), respectively. Compared with participants without hypertension and a Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios (95% confidence intervals) for the participants with hypertension and Cum-non-HDL-Cs < 130 mg/dl, 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.84 (1.55, 2.18), 2.16 (1.81, 2.59), 2.17 (1.73, 2.70), and 2.45 (1.12, 3.29), respectively. CONCLUSIONS: A consistently high non-HDL-C concentration increases the risk of CVD in individuals with hypertension, as does prolonged exposure to a high non-HDL-C concentration. Thus, the achievement of target blood pressure and non-HDL-C concentrations should help reduce the risk of CVD in individuals with hypertension.

Cumulative exposure to poor housing conditions and psychological well-being: Does the relationship differ for young and middle-aged adults and older adults?

OBJECTIVES: This study examined whether cumulative exposure to poor housing conditions is negatively associated with psychological well-being, and whether this association varies by age. METHODS: Using fifteen waves of the Korean Welfare Panel Study between 2005 and 2019 (118,500 person-observations), this study employed fixed-effects regression models to account for unobserved individual-level heterogeneity. Exposure to poor housing conditions ranged from 1 to more than 5 annual waves. To formally test for age heterogeneity, interactive models were estimated. RESULTS: The trajectories of change in psychological well-being associated with cumulative exposure to poor housing conditions were different between young and middle-aged adults and older adults. Among young and middle-aged adults, the levels of depressive symptoms increased in the first year of exposure but remained at a similar level since then. In contrast, with the persistence of poor housing conditions, older adults continued to develop greater depressive symptoms over time. Similar age differences were found for life satisfaction. As exposure to poor housing conditions accumulated, life satisfaction persistently declined among older adults, but not young and middle-aged adults. CONCLUSION: This study suggests that cumulative exposure to poor housing conditions has more adverse psychological consequences for older adults than young and middle-aged adults.

Prolonged social isolation and cognitive function in older adults: lack of informal social contact versus formal social activity as the source of social isolation.

OBJECTIVES: This study investigates the cognitive function trajectories associated with prolonged social isolation, while distinguishing between a lack of informal social contact and a lack of formal social activity as the source of social isolation. METHODS: Data from the Korean Longitudinal Study of Ageing spanning 12 years between 2006 and 2018 were analyzed. A lack of frequent informal social contact or formal social activity was used to assess social isolation, and cognitive function was measured by Korean Mini-Mental State Examination. Fixed effects regression models were used to account for unobserved individual-level confounders. RESULTS: A prolonged absence of frequent informal social contact was linked to a decline in cognitive function up to the three waves of exposure (b = -2.135), but cognitive function has not declined further since then. A persistent lack of formal social activity was associated with a decline in cognitive function up to the fifth and subsequent waves of exposure (b = -3.073). No gender differences were observed in these relationships. CONCLUSION: Prolonged social isolation, particularly a lack of formal social activity, can pose a significant threat to the cognitive health of older adults.

Cumulative risk assessment of the dietary heavy metal and aluminum exposure of Finnish adults.

While directly comparable toxicological data are unavailable, this pilot study used published toxicological endpoints for neurological damage to weigh the relative importance of cadmium, lead, arsenic, mercury, nickel, and aluminum in the mixture Finnish adults receive from their daily diet. In addition, the effects of a selection of these chemicals on cognition, kidney tubular damage, and fertility were assessed using the toxicological endpoints available in the Chemical Mixture Calculator developed by the Technical University of Denmark. Consumption data from the FinDiet 2012 national survey of 25 to 74-year-olds and occurrence data mainly obtained in national monitoring were used to estimate the cumulative dietary exposure, which was found to be so high that the possibility of neurological damage or kidney effects cannot be ruled out for most of the population, particularly fertile age women. For Finns below the age of 65 years, the main sources of cumulative exposure were bread and other cereals, non-alcoholic drinks, and vegetables. When mean exposure was statistically compared between age groups and genders, women aged 25 to 45 years had a statistically significantly higher exposure than men of the same age (P < 0.05) and women aged 46 to 64 years (P < 0.001).

Unpacking the Meaning of Closeness, Reconsidering the Concept of Impact in Suicide Exposure, and Expanding Beyond Bereavement: "Just, I Hope You Don't Forget About Us".

Suicide exposure research has relied on samples of treatment-seeking kin, resulting in an attachment-based model centering bereavement as the most significant form of impact and obscuring other forms of significant and life-altering impact. From a community-based sample (N = 3010) exposed to suicide, we examine a subset (n = 104) with perceived high impact from the death yet low reported closeness to the person who died and analyze qualitative comments (n = 50). On average and out of 5.00, participants rated closeness as 1.56 but impact of death as 4.51. We illustrate dimensions of low closeness and identify themes on the meaning of impact: impact through society and systemic circumstances, impact through history and repeated exposure, impact through other people, impact as a motivator for reflection or change, and impact through shared resonance. Participants reported impact of death as significant or devastating, yet none of their comments reflected experiences typical of bereavement.