Risk Of Cardiovascular Disease Death Research Articles

Higher Dietary Inflammatory Index and Increased Mortality Rate of Adults With Hyperuricemia: Findings From the National Health and Nutritional Examination Survey (2001-2018).

This study aimed to assess the association between Dietary Inflammatory Index (DII) score and death among adults with hyperuricemia. We collected data from the 2001 to 2018 cohorts of the National Health and Nutritional Examination Survey. Death information was obtained based on death certificate records from the National Death Index through December 31, 2019. The associations between DII score and all-cause, cardiovascular disease (CVD), and cancer death were investigated by using Cox proportional hazards regression models. We enrolled 7,786 participants with hyperuricemia in this study. The DII score ranged from -4.42 to 4.61. Higher DII score was significantly associated with higher levels of body mass index, glycohemoglobin, glucose, low-density lipoprotein-cholesterol, and C-reactive protein (all P < 0.05). During 67,851 person-years of follow-up, deaths of 1,456 participants were identified, including 532 CVD deaths and 246 cancer deaths. After adjusting for potential variables, significant higher risk of all-cause (hazard ratio [HR] 1.18, 95% confidence interval [95% CI] 1.03-1.36, P = 0.01) and CVD (HR 1.30, 95% CI 1.03-1.63, P = 0.02) death was observed for individuals with higher DII scores. Considering the DII score as a continuous variable, the risk of all-cause and CVD death increases 5% (HR 1.05, 95% CI 1.01-1.08) and 8% (HR 1.08, 95% CI 1.02-1.15) with each one-unit increment in DII score, respectively. Subgroup analysis indicated that the association between DII score and all-cause death among participants with hyperuricemia was more significant in males. DII score is found to be positively associated with all-cause and CVD death of adults with hyperuricemia. Controlling the intake of proinflammatory food might be a potential strategy to reduce the mortality rate.

A prospective cohort study of exposure to household pesticide with cardiovascular diseases mortality in older adults

ObjectivesWe examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). MethodsInformation on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. ResultsThe participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. ConclusionsExposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model.

Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors. To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients. This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA). The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit. Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

Relationship between serum phosphorus and mortality in non-dialysis chronic kidney disease patients: evidence from NHANES 2001–2018

BackgroundHyperphosphatemia is common in chronic kidney disease (CKD), associated with higher mortality in dialysis patients. Its impact in non-dialysis patients, especially those with preserved kidney function, remains uncertain.MethodsA prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (2001–2008). Serum phosphorus was analyzed as a continuous variable, or categorized into three groups: < 3.5 mg/dL, 3.5 to < 4.5 mg/dL, and ≥ 4.5 mg/dL. Cox proportional hazards models were used to analyze the association between phosphorus with all-cause and cardiovascular disease (CVD) mortality, with or without adjustment for age, sex, race, hemoglobin, estimated glomerular filtration rate (eGFR), serum albumin, serum calcium, 25(OH)D, obesity, hypertension, diabetes, and CVD.ResultsA total of 7694 participants were included in the analysis, representing 28 million CKD patients in the United States. During mean 92 months of follow up, 2708 all-cause deaths (including 969 CVD deaths) were observed. Per 1 mg/dL increase in phosphorus was associated with a 13% and 24% increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95%CI, 1.02–1.24) and CVD mortality (HR, 1.24; 95%CI, 1.07–1.45), respectively. Compared with the < 3.5 mg/dL, phosphorus ≥ 4.5 mg/dL was associated with a 28% and 57% increased risk of all-cause mortality (HR, 1.28; 95%CI, 1.05–1.55) and CVD mortality (HR, 1.57; 95CI, 1.19–2.08), respectively. In participants with eGFR < 60 ml/min/1.73m2, elevated phosphorus (≥ 4.5 mg/ dL) were significantly associated with increased risk of all-cause mortality (HR, 1.36; 95%CI, 1.07–1.72). No significant association was observed in eGFR ≥ 60 ml/min/1.73m2 group (HR, 1.31; 95%CI, 0.86–1.99). This correlation does not differ significantly between subgroups defined by eGFR level (P for interaction = 0.889).ConclusionSerum phosphorus above 4.5 mg/dL is significantly associated with a 28% and 57% increased risk of all-cause and CVD death in non-dialysis CKD patients, respectively. This relationship still demonstrated in patients with eGFR < 60 ml/min/1.73m2. However, for population with eGFR ≥ 60 ml/min/1.73m2, further verification is needed.

Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers

IntroductionPrevious studies on cardiovascular disease (CVD) death risk in cancer patients mostly focused on overall cancer, age subgroups and single cancers. ObjectivesTo assess the CVD death risk in non-metastatic cancer patients at 21 cancer sites. MethodsA total of 1,672,561 non-metastatic cancer patients from Surveillance, Epidemiology, and End Results (SEER) datebase (1975–2018) were included in this population-based study, with a median follow-up of 12·7 years. The risk of CVD deaths was assessed using proportions, competing-risk regression, absolute excess risks (AERs), and standardized mortality ratios (SMRs). ResultsIn patients with localized cancers, the proportion of CVD death and cumulative mortality from CVD in the high-competing risk group (14 of 21 unique cancers) surpassed that of primary neoplasm after cancer diagnosis. The SMRs and AERs of CVD were found higher in patients with non-metastatic cancer than the general US population (SMR 1·96 [95 %CI, 1·95-1·97]–19·85[95 %CI, 16·69-23·44]; AER 5·77–210·48), heart disease (SMR 1·94[95 %CI, 1·93-1·95]–19·25[95 %CI, 15·76-23·29]; AER 4·36–159·10) and cerebrovascular disease (SMR 2·05[95 %CI, 2·02-2·08]–24·71[95 %CI, 16·28-35·96]; AER 1·01–37·44) deaths. In the high-competing risk group, CVD-related SMR in patients with localized stage cancer increased with survival time but followed a reverse-dipper pattern in the low-competing risk group (7 of 21 cancers). The high-competing risk group had higher CVD-related death risks than the low-competing risk group. ConclusionThe CVD death risk in patients with non-metastatic cancer varied by cancer stage, site and survival time. The risk of CVD mortality is higher in 14 out of 21 localized cancers (high-competing cancers). Targeted strategies for CVD management in non-metastatic cancer patients are needed.

Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study.

Women with breast cancer are at higher risk of cardiovascular disease (CVD) compared with women without breast cancer. Whether higher diet quality at breast cancer diagnosis lowers this risk remains unknown. We set out to determine if higher diet quality at breast cancer diagnosis was related to lower risk of CVD and CVD-related death. This analysis included 3415 participants from the Pathway Study, a prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through December 31, 2021. Scores from 5 diet quality indices consistent with healthy eating were obtained at the time of breast cancer diagnosis. Scores were categorized into ascending quartiles of concordance for each diet quality index, and multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. P values were 2-sided. The Dietary Approaches to Stop Hypertension diet quality index was associated with lower risk of heart failure (HR = 0.53, 95% CI = 0.33 to 0.87; Ptrend = .03), arrhythmia (HR = 0.77, 95% CI = 0.62 to 0.94; Ptrend = .008), cardiac arrest (HR = 0.77, 95% CI = 0.61 to 0.96; Ptrend = .02), valvular heart disease (HR = 0.79, 95% CI = 0.64 to 0.98; Ptrend = .046), venous thromboembolic disease (HR = 0.75, 95% CI = 0.60 to 0.93; Ptrend = .01), and CVD-related death (HR = 0.70, 95% CI = 0.50 to 0.99; Ptrend = .04), when comparing the highest with lowest quartiles. Inverse associations were also found between the healthy plant-based dietary index and heart failure (HR = 0.60, 95% CI = 0.39 to 0.94; Ptrend = .02), as well as the alternate Mediterranean dietary index and arrhythmia (HR = 0.74, 95% CI = 0.60 to 0.93; Ptrend = .02). Among newly diagnosed breast cancer patients, higher diet quality at diagnosis was associated with lower risk of CVD events and death.

Differential associations of fetuin-A and calcification propensity with cardiovascular events and subsequent mortality in patients undergoing hemodialysis.

Fetuin-A inhibits precipitation of calcium-phosphate crystals by forming calciprotein particles (CPP). A novel T50 test, which measures transformation time from primary to secondary CPP, is an index for calcification propensity. Both lower fetuin-A and shorter T50 levels were associated with cardiovascular disease (CVD) risk in patients with chronic kidney disease (CKD). Extremely high risk for CVD death in advanced CKD patients consists of high-incidental CVD event and high mortality after CVD event. To date, it is unclear whether fetuin-A and/or T50 can equally predict each CVD outcome. This prospective cohort study examined patients undergoing maintenance hemodialysis. The exposures were fetuin-A and T50. The outcomes of interests were new CVD events and subsequent deaths. The patients were categorized into tertiles of fetuin-A or T50 (T1 to T3). We identified 190 new CVD events during the 5-year follow-up of the 513 patients and 59 deaths subsequent to the CVD events during 2.5-year follow-up. A lower fetuin-A but not T50 was significantly associated with new CVD events [subdistribution hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.15-2.61, P=.009 for T1 vs T3]. In contrast, a shorter T50 but not fetuin-A was a significant predictor of deaths after CVD events (HR 3.31, 95% CI 1.42-7.74, P=.006 for T1+T2 vs T3). A lower fetuin-A was predictive of new CVD events, whereas a shorter T50 was more preferentially associated with subsequent death. These results indicate that fetuin-A and T50 are involved in cardiovascular risk in different manners.

Prospective Associations of Accelerometer-Measured Machine-Learned Sedentary Behavior With Death Among Older Women: The OPACH Study.

Sedentary behavior is a recognized mortality risk factor. The novel and validated convolutional neural network hip accelerometer posture algorithm highly accurately classifies sitting and postural changes compared with accelerometer count cut points. We examined the prospective associations of convolutional neural network hip accelerometer posture-classified total sitting time and mean sitting bout duration with all-cause and cardiovascular disease (CVD) death. Women (n=5856; mean±SD age, 79±7 years; 33% Black women, 17% Hispanic or Latina women, 50% White women) in the Women's Health Initiative Objective Physical Activity and Cardiovascular Health (OPACH) Study wore the ActiGraph GT3X+ for ~7 days from May 2012 to April 2014 and were followed through February 19, 2022 for all-cause and CVD death. The convolutional neural network hip accelerometer posture algorithm classified total sitting time and mean sitting bout duration from GT3X+ output. Over follow-up (median, 8.4 years; range, 0.1-9.9), there were 1733 deaths (632 from CVD). Adjusted Cox regression hazard ratios (HRs) comparing women in the highest total sitting time quartile (>696 min/d) to those in the lowest (<556.0 min/d) were 1.57 (95% CI; 1.35-1.83; P-trend<0.001) for all-cause death and 1.78 (95% CI; 1.36-2.31; P-trend<0.001) for CVD death. HRs comparing women in the longest mean sitting bout duration quartile (>15 minutes) to the shortest (<9.3 minutes) were 1.43 (95% CI; 1.23-1.66; P-trend<0.001) for all-cause death and 1.52 (95% CI; 1.18-1.96; P-trend<0.001) for CVD death. Apparent nonlinear associations for total sitting time suggested higher all-cause death (P nonlinear=0.009) and CVD death (P nonlinear=0.008) risk after ~660 to 700 min/d. Higher total sitting time and longer mean sitting bout duration are associated with higher all-cause and CVD mortality risk among older women. These data support interventions aimed at reducing both total sitting time and interrupting prolonged sitting.

Associations of trajectories in body roundness index with incident cardiovascular disease: a prospective cohort study in rural China.

The body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China. In total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004-2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD. Three distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged <50 years. BRI trajectory was positively associated with incident CVD, providing a novel possibility for the primary prevention of CVD in rural regions of China.

Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study

BackgroundHigher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes.MethodsA total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes.ResultsFractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20–6.22).ConclusionsElevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.

Serum apolipoproteins and mortality risk: evidence from observational and Mendelian randomization analyses

BackgroundApolipoproteins (APOs) have emerged as significant players in lipid metabolism that affects the risk of chronic disease. However, the impact of circulating APO concentrations on premature death remains undetermined. ObjectivesThis study aimed to investigate the associations of serum APOs with all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality. MethodsWe included 340,737 participants who had serum APO measurements from the UK Biobank. Restricted cubic splines and multivariable Cox regression models were used to assess the associations between APOs and all-cause and cause-specific mortality by computing hazard ratios (HRs) and 95% confidence intervals (CIs). Based on 1-sample Mendelian randomization (MR) design, including 398,457 participants of White ancestry who had genotyping data from the UK Biobank, we performed instrumental variable analysis with 2-stage least squares regression to assess the association between genetically predicted APOs and mortality. ResultsAfter adjusting for potential confounders including high-density and low-density lipoprotein particles, we observed nonlinear inverse relationships of APOA1 with all-cause, CVD-related, and cancer-related mortality (P-nonlinear < 0.001). By contrast, positive relationships were observed for APOB and all-cause (P-nonlinear < 0.001), CVD-related (P-linear < 0.001), and cancer-related (P-linear = 0.03) mortality. MR analysis showed consistent results, except that the association between APOB and cancer mortality was null. Furthermore, both observational and MR analyses found an inverse association between APOA1 and lung cancer–related mortality (HR comparing extreme deciles: 0.46; 95% CI: 0.26, 0.80; and HR: 0.78; 95% CI: 0.63, 0.97, respectively). ConclusionsOur findings indicate that circulating APOA1 has potential beneficial effects on all-cause, CVD-related, and lung cancer–related death risk, whereas APOB may confer detrimental effects on all-cause and CVD-related death risk.

External validation of a multi-biomarker-based score for predicting risk of cardiovascular disease in patients with rheumatoid arthritis.

A multi-biomarker disease activity (MBDA)-based cardiovascular disease (CVD) risk score was developed and internally validated in a Medicare cohort to predict 3-year risk for myocardial infarction (MI), stroke or CVD death in patients with rheumatoid arthritis (RA). It combines the MBDA score, leptin, MMP-3, TNF-R1, age and four clinical variables. We are now externally validating it in a younger RA cohort. Claims data from a private aggregator were linked to MBDA test data to create a cohort of RA patients ≥18 years old. A univariable Cox proportional hazards regression model was fit using the MBDA-based CVD risk score as sole predictor of time-to-a-CVD event (hospitalized MI or stroke). Hazard ratio (HR) estimate was determined for all patients and for clinically relevant subgroups. A multivariable Cox model evaluated whether the MBDA-based CVD risk score adds predictive information to clinical data. 49,028 RA patients (340 CVD events) were studied. Mean age was 52.3 years; 18.3% were male. HR for predicting 3-year risk of a CVD event by the MBDA-based CVD risk score in the full cohort was 3.99 (95% CI: 3.51-4.49, p = 5.0×10-95). HR were also significant for subgroups based on age, comorbidities, disease activity, and drug use. In a multivariable model, the MBDA-based CVD risk score added significant information to hypertension, diabetes, tobacco use, history of CVD, age, sex and CRP (HR = 2.27, p = 1.7×10-7). The MBDA-based CVD risk score has been externally validated in an RA cohort that is younger than and independent of the Medicare cohort that was used for development and internal validation.

Cholesterol paradox in the community-living old adults: is higher better?

To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Circulating oxysterols and prognosis among women with a breast cancer diagnosis: results from the MARIE patient cohort

BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide, and underlying mechanistic pathways associated with breast cancer-specific and non-breast cancer-related deaths are of importance. Emerging evidence suggests a role of oxysterols, derivates of cholesterol, in multiple chronic diseases including breast cancer and coronary artery diseases. However, associations between oxysterols and survival have been minimally studied in women diagnosed with breast cancer. In this large breast cancer patient cohort, we evaluated associations between a panel of circulating oxysterols and mortality and recurrence outcomes.MethodsConcentrations of 13 circulating oxysterols representing different pathways of cholesterol metabolism were quantified using liquid-chromatography mass-spectrometry. Associations between baseline levels of oxysterols and cause-specific mortality outcomes and recurrence following a breast cancer diagnosis were assessed in 2282 women from the MARIE study over a median follow-up time of 11 years. We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazard models and competing risks models.ResultsWe observed no associations for circulating oxysterols and breast cancer-specific outcomes. Higher levels of six oxysterols were associated with an increased risk of cardiovascular disease death, including 24S-hydroxycholesterol (alternative bile acid pathway, HRlog2 = 1.73 (1.02, 2.93)), lanosterol (cholesterol biosynthesis pathway, HRlog2 = 1.95 (1.34, 2.83)), 7-ketocholesterol (HRlog2 = 1.26 (1.03, 1.55)), 5α,6α-epoxycholesterol (HRlog2 = 1.34 (1.02–1.77)), and 5a,6β-dihydroxycholestanol (HRlog2 = 1.34 (1.03, 1.76)). After adjusting for multiple comparisons, none of the associations were statistically significant.ConclusionWe provide first evidence on a range of circulating oxysterols and mortality following a breast cancer diagnosis, contributing to a better understanding of associations between different pathways of cholesterol metabolism and prognosis in women with a breast cancer diagnosis. The findings of this study suggest circulating oxysterols may be associated with cardiovascular mortality among women diagnosed with breast cancer. Further studies are needed to evaluate these oxysterols as potential markers of risk for cardiovascular mortality among women with a breast cancer diagnosis as well as their clinical potential.

Long-term cardiovascular risk of pre-eclampsia

Abstract Background/introduction Pre-eclampsia is a complication of the second and third trimesters of pregnancy characterized by hypertension and endothelial dysfunction causing multiorgan damage. In 2017 few studies suggested an association between pre-eclampsia and long-term cardiovascular diseases. However, since those first studies, the literature has grown exponentially. Purpose To assess the association between a history of pre-eclampsia and subsequent cardiovascular diseases, including 1) cardiovascular death, 2) coronary heart disease, 3) heart failure, and 4) stroke. Methods Following PRISMA guidelines, from inception to September 2022, we performed a systematic review of PubMed, MEDLINE, Scopus, and EMBASE. Randomized, cohort or case-control studies in English were included if fulfilling the following criteria: 1) the association between pre-eclampsia and subsequent cardiovascular disease was adjusted for at least maternal age, smoking, and obesity; 2) the presence of a control group; 3) minimum one-year follow-up. Pooled Relative Risk (RRs) and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model. The primary endpoint was cardiovascular death. The secondary endpoints were coronary heart disease, heart failure, and stroke. Results Twenty-one studies met the inclusion criteria, including 478,708 women with a history of pre-eclampsia and 10,533,530 without. Pre-eclampsia was associated with a higher risk of cardiovascular disease death (RR 1.97, 95% CI 1.64-2.35, I2 60%, p&amp;lt;0.00001), coronary heart disease (RR 2.11, 95% CI 1.60-2.77, I2 85%, p&amp;lt;0.00001), heart failure (RR 2.47, 95% CI 1.70-3.59, I2 82%, p&amp;lt;0.00001), and stroke (RR 1.64, 95% CI 1.45-1.85, I2 43%, p&amp;lt;0.00001). Sensitivity analysis excluding those studies with a follow-up of less than 10 years evidenced similar results. Conclusions Compared to women who experienced a normal pregnancy, those suffering from pre-eclampsia have about double the risk of cardiovascular disease, including cardiovascular death, coronary heart disease, heart failure, and stroke. This risk becomes evident already in the first ten years after pregnancy. As such, obstetricians should counsel pre-eclamptic women on the importance of an early assessment and risk factors management in a multidisciplinary team with cardiologists.

THU652 Associations Of Testosterone, Dihydrotestosterone, Estradiol And Sex Hormone-binding Globulin With All-cause And Cardiovascular Mortality, And Incident Cardiovascular Events In Men: Individual Participant Data Meta-analyses

Abstract Disclosure: B.B. Yeap: None. R.J. Marriott: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. K. Murray: None. Studies examining associations of circulating sex steroids with mortality risk in men show inconsistent results for testosterone (T), with limited data for dihydrotestosterone (DHT) and estradiol (E2). We aimed to clarify associations of sex steroids, sex hormone-binding globulin (SHBG) and luteinising hormone (LH) with risks of all-cause and cardiovascular disease (CVD) mortality and incident CVD events in men, by conducting individual participant data (IPD) meta-analyses of prospective cohort studies with sex steroids measured using mass spectrometry. The Androgens In Men Study protocol was registered (PROSPERO: CRD42019139668) and published (BMJ Open 2020;10:e034777). A systematic review (completed Dec 2019) identified relevant studies (BMJ Open 2021;11:e048013). IPD were requested. Cox proportional hazards analyses related total T, SHBG, LH, DHT and E2 concentrations to risk of all-cause mortality and CVD deaths, and risk of incident CVD events. Models were adjusted for age and other sociodemographic factors, lifestyle factors, medical conditions and medications. Summary curves and hazard ratios (HRs) with 95% confidence intervals (CIs) were determined using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (24,596 men), with median baseline age 49-76 years and 4-20 years follow-up among studies. Associations of T with all-cause and CVD mortality risk were non-linear. Risk of all-cause mortality increased for men with baseline T concentrations &amp;lt;8.7 nmol/L, and risk of CVD death increased for men with baseline T &amp;lt;5.3 nmol/L. Lower SHBG concentrations were associated with lower risk of all-cause mortality (median Quintile [Q]1 vs Q5 [Q1:Q5], 20.6 vs 68.3 nmol/L; HR=0.85, CI=0.77-0.95), and CVD death (HR=0.81, CI 0.65-1.00). Men with LH &amp;gt;10 IU/L or E2 &amp;lt;5.1 pmol/L had higher all-cause mortality, with no association of LH or E2 with CVD deaths. Associations of DHT with all-cause and CVD mortality risk were non-linear. Men with lower baseline DHT concentrations had higher risk of all-cause mortality (median Q1:Q5, 0.69 vs 2.45 nmol/L; HR=1.19, CI=1.08-1.30) and CVD deaths (HR=1.29, CI=1.03-1.61), with risk increasing for DHT &amp;gt;2.45 nmol/L. Men with baseline DHT concentrations &amp;lt;0.59 nmol/L had increased risk of incident CVD events, no other hormones were associated with this outcome. Our results suggest greater all-cause and CVD mortality risk among men with very low baseline T, higher baseline SHBG, or either lower or very high baseline DHT concentrations. There was greater risk of CVD events among men with very low baseline DHT concentrations. Potential mechanisms by which SHBG and DHT might influence mortality risk in ageing men merit further investigation. Presentation: Thursday, June 15, 2023

Risk of cardiovascular disease in cancer survivors: A cohort study of 446,384 New Zealand primary care patients.

Given advances in the management of cancer, it is increasingly important for clinicians to appropriately manage the risk of cardiovascular disease (CVD) among cancer survivors. It is unclear whether CVD risk is increased among cancer survivors overall, and there is inconsistency in evidence to date about CVD incidence and mortality by cancer type. Patients aged 30-74 years entered an open cohort study at the time of first CVD risk assessment, between 2004 and 2018, in primary care in New Zealand. Patients with established CVD or cancer within 2 years prior to study entry were excluded. Cancer diagnosis (1995-2016) was determined from a national cancer registry. Cause-specific hazard models were used to examine the association between history of cancer and two outcomes: (1) CVD-related hospitalization and/or death and (2) CVD death. The study included 446,384 patients, of whom 14,263 (3.2%) were cancer survivors. Risk of CVD hospitalization and/or death was increased among cancer survivors compared with patients without cancer at cohort entry (multivariable-adjusted hazard ratio, mHR, 1.11, 95% CI 1.05-1.18), more so for CVD death (1.31, 1.14-1.52). Risk of CVD hospitalization and/or death was increased in patients with myeloma (2.66, 1.60-4.42), lung cancer (2.19, 1.48-3.24) and non-Hodgkin lymphoma (1.90, 1.42-2.54), but not for some cancers (e.g., colorectal, 0.87, 0.71-1.06). Risk of CVD death was increased in several cancer types including melanoma (1.73, 1.25-2.38) and breast cancer (1.56, 1.16-2.11). CVD risk management needs to be prioritized among cancer survivors overall, and particularly in those with myeloma, lung cancer and non-Hodgkin lymphoma given consistent evidence of increased risk.

Association of Magnesium Depletion Score With Cardiovascular Disease and Its Association With Longitudinal Mortality in Patients With Cardiovascular Disease.

Background Dietary magnesium and serum magnesium play an important part in cardiovascular disease (CVD). However, the association between magnesium depletion score (MDS) and CVD development and prognosis remains unclear. This analysis examines the cross-sectional relationship between MDS and CVD, and the longitudinal association between MDS and all-cause and CVD mortality in individuals with CVD. Methods and Results In all, 42 711 individuals were selected from the National Health and Nutrition Examination Survey, including 5015 subjects with CVD. The association between MDS and total and individual CVDs was examined using the survey-weighted multiple logistic regression analysis. Among 5011 patients with CVD, 2285 and 927 participants were recorded with all-cause and CVD deaths, respectively. We applied survey-weighted Cox proportional hazards regression analyses to investigate the impact of MDS on the mortality of individuals with CVD. The CVD group had higher MDS levels than the non-CVD groups. After controlling all confounding factors, individuals with MDS of 2 and ≥3 had higher odds of total CVD and specific CVD than those with MDS of 0. Besides, each 1-unit increase in MDS was strongly related to the risk of total CVD and specific CVD. The relationship between MDS and total CVD was stable and significant in all subgroups. The fully adjusted Cox regression model indicated that high MDS, irrespective of MDS as a categorical or continuous variable, was significantly associated with an elevated risk of all-cause and CVD deaths. Conclusions MDS is a vital risk factor for the prevalence and mortality of individuals with CVD.

Effect of overall lifestyle on the all-cause mortality and cardiovascular disease death in dyslipidemia patients with or without lipid-lowering therapy: a cohort study

BackgroundLifestyle adjustment has been reported as one of the interventions for dyslipidemia. This study aimed to explore the effect of overall lifestyle on the risk of all-cause mortality and cardiovascular disease (CVD) death in dyslipidemia patients with or without lipid-lowering therapy.MethodsThis was a retrospective cohort study, and data were extracted from the National Health and Nutrition Examination Survey (NHANES). Overall lifestyle was assessed based on Mediterranean diet score, physical activity, smoking status, sleep duration, and body mass index (BMI). Multivariate Cox regression model was used to explore the effect of overall lifestyle score on the risk of all-cause mortality and CVD death. Results were shown as hazard ratio (HR), with 95% confidence interval (CI).ResultsA total of 11,549 dyslipidemia patients were finally included in this study. The results showed that optimal overall lifestyle was associated with the decreased risk of all-cause mortality (HR = 0.47, 95%CI: 0.34–0.64) and CVD death (HR = 0.45, 95%CI: 0.22–0.94) in patients without lipid-lowering therapy. The similar results were found in patients with lipid-lowering therapy (all-cause mortality: HR = 0.45, 95%CI: 0.33–0.62; CVD death: HR = 0.38, 95%CI: 0.23–0.63).ConclusionsA favorable overall lifestyle may have great benefits to improve the prognosis of dyslipidemia, highlighting the importance of overall lifestyle adjustment for dyslipidemia patients.

Cardiovascular mortality by cancer risk stratification in patients with localized prostate cancer: a SEER-based study.

The risk of cardiovascular disease (CVD) mortality in patients with localized prostate cancer (PCa) by risk stratification remains unclear. The aim of this study was to determine the risk of CVD death in patients with localized PCa by risk stratification. Population-based study of 340,806 cases in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with localized PCa between 2004 and 2016. The proportion of deaths identifies the primary cause of death, the competing risk model identifies the interaction between CVD and PCa, and the standardized mortality rate (SMR) quantifies the risk of CVD death in patients with PCa. CVD-related death was the leading cause of death in patients with localized PCa, and cumulative CVD-related death also surpassed PCa almost as soon as PCa was diagnosed in the low- and intermediate-risk groups. However, in the high-risk group, CVD surpassed PCa approximately 90 months later. Patients with localized PCa have a higher risk of CVD-related death compared to the general population and the risk increases steadily with survival (SMR = 4.8, 95% CI 4.6-5.1 to SMR = 13.6, 95% CI 12.8-14.5). CVD-related death is a major competing risk in patients with localized PCa, and cumulative CVD mortality increases steadily with survival time and exceeds PCa in all three stratifications (low, intermediate, and high risk). Patients with localized PCa have a higher CVD-related death than the general population. Management of patients with localized PCa requires attention to both the primary cancer and CVD.