Multivariable-adjusted HRs Research Articles

Remnant Cholesterol and New-onset Atrial Fibrillation: The Atherosclerosis Risk in Communities Study

BackgroundThe relationship between remnant cholesterol (RC) and atrial fibrillation (AF) remains unclear. ObjectiveTo comprehensively explore the association between RC characteristics and new-onset AF. MethodsData from five follow-up visits of the ARIC study were analyzed. RC were multidimensionally evaluated in four characteristics, including baseline level, variability, cumulative exposure and trajectory. Baseline RC was obtained from the initial visit (V1), and new-onset AF was monitored in V2 to V5 (cohort 1, n=14450). RC variability, cumulative RC and RC trajectory were calculated by RC values gathered from V1 to V3, and new-onset AF was monitored in V4 and V5 (cohort 2, n=11012). Participants were divided into four groups based on quartiles or trajectories. Cox proportional hazards analyses were used to investigate the relationship between RC characteristics and AF. ResultsFollowing a median follow-up of 22.39 years in cohort 1 and 16.71 years in cohort 2, a total of 1993 AF events in cohort 1 and 1571 in cohort 2 were identified. Participants with the highest quartile exhibited an elevated risk of new-onset AF, with the multivariable-adjusted HRs of 1.35 (P=0.009) for baseline RC and 1.26 (P=0.09) for RC variability. Although the highest quartile of cumulative RC (P=0.130) and the high-increasing trajectory (P=0.322) did not demonstrate a statistically significant association with AF occurrence, they indicate a trend towards a heightened risk. ConclusionOur findings reveal that higher levels of RC, particularly at baseline and in variability, are associated with an increased risk of AF.

Effect of dietary live microbe intake on the prevalence and mortality risks of depression and suicidal ideation in adults: Evidence from a nationwide population-based study

BackgroundGut microbial dysbiosis has been implicated in the pathogenesis of depression. Dietary interventions offer promising microbial-targeted therapeutics for depression. However, limited evidence exists regarding the associations between dietary live microbe intake and the prevalence of depression, as well as its impact on mortality risks. MethodsThis study included 28,133 participants from the U.S. National Health and Nutrition Examination Survey (2005–2018), and ascertained their underlying causes of death. Weighted logistic regression was utilized to assess the relationships between live microbe intake and risks of depression and suicidal ideation. Independent and joint associations between live microbe and mortality outcomes were evaluated using multivariable Cox regression and Kaplan-Meier survival curves to calculate relative risks. ResultsIn the fully adjusted model, participants with high dietary live microbe intake had a significantly lower prevalence of depression (OR = 0.727, 95%CI: 0.627,0.844) and suicidal ideation (OR = 0.778, 95%CI: 0.648,0.935) than those with low intake. The multivariable-adjusted HRs for individuals in the G1 were 1.217 (95%CI, 1.081, 1.370) for all-cause mortality and 1.307 (95%CI, 1.029,1.661) for cardiovascular disease mortality, compared to participants in the G3. Kaplan-Meier survival analysis revealed that cumulative hazard of cardiovascular mortality was progressively lower among participants with depression in the G3 than those without depression. ConclusionsHigher live microbe intake was associated with a lower prevalence of depression and suicidal ideation, and was linked to significantly decreased risks of all-cause and cardiovascular mortality. Further larger prospective studies are essential to verify the health effects of live microbes, and personalized dietary recommendations are necessary.

Baseline renal function modified the association between total, plant or animal protein intake and the risk of developing renal composite outcome in people with type 2 diabetes: a prospective cohort study [diabetes distress and care registry at Tenri (DDCRT25)

This study aimed to identify the longitudinal associations between protein intake, and composite renal outcomes in people with type 2 diabetes. To examine the association between baseline total, animal, and plant protein intake and the risk of developing a composite renal outcome in 3,109 Japanese people with type 2 diabetes who participated in a cohort study at a tertiary care hospital, we used a Cox proportional hazards model. During a median follow-up of 6.0years, we observed 185 renal outcomes. Compared with the 1st quintile, the multivariable-adjusted HRs for outcome were 1.13 (p = 0.440), 1.04 (pp= 0.874), 1.40 (p = 0.215), and 2.16 (p = 0.001), respectively for the 2nd to 5th quintile of total protein intake, and 0.93 (p = 0.681), 1.1 (p= 0.596), 1.1 (p = 0.607), and 2.02 (p < 0.001), respectively for the 2nd to 5th quintile of animal protein intake. However, a significant association of total plant intake was not observed. In the analysis evaluating the joint association between protein intake and composite renal outcome with baseline estimated glomerular filtration ratio (eGFR), total protein and animal protein intake were substantially associated with a higher risk of composite renal outcome when the baseline eGFR was below approximately 60mL/min/1.732. Baseline total protein intake is associated with a higher risk of developing a composite renal outcome during follow-up in people with type 2 diabetes and low baseline eGFR, and this association may be elucidated by a higher animal protein intake. Plant protein was not associated with renal outcome.

Long-term association of remnant cholesterol with all-cause and cardiovascular disease mortality: a nationally representative cohort study.

Despite reducing low-density lipoprotein cholesterol (LDL-C) to the normal range, residual cardiovascular risk remain. Remnant cholesterol (RC) exerts a potential residual risk for cardiovascular disease (CVD) prevention, and the long-term longitudinal association between RC and mortality has yet to be well elucidated. This study examined a nationally representative sample of 13,383 adults aged 20 years or older (mean age 45.7 and 52% women) who participated in the NHANES III (from1988 to1994). Causes of death were ascertained by linkage to death records through December 31, 2019. The relations of RC with all-cause and CVD mortality were tested using weighted Cox proportional hazard models. Through a median follow-up of 26.6 years, 5,044 deaths were reported, comprising 1,741 deaths of CVD [1,409 deaths of ischemic heart disease (IHD) and 332 deaths of stroke] and 1,126 of cancer. Compared to those with RC <14.26 mg/dl (lowest quartile), participants with RC ≥29.80 mg/dl (highest quartile) had multivariable-adjusted HRs of 1.23 (95% CI: 1.07-1.42) for all-cause mortality, 1.22 (95% CI: 0.97-1.53) for CVD mortality, and 1.32 (95% CI: 1.03-1.69) for IHD mortality, and 0.89 (95% CI: 0.55-1.43) for stroke mortality, and 1.17 (95% CI 0.90-1.52) for cancer mortality. We observed that elevated RC levels increased CVD risk and IHD mortality despite LDL-C being in the normal range. Elevated blood RC was associated with an increased long-term risk of all-cause, CVD, and IHD mortality. These associations were independent of socioeconomic factors, lifestyles, and history of diseases, and remained robust across the LDL-C stratum. Measuring RC levels might favor clinical assessment of early CVD risk. Further investigation is needed to elucidate the optimal range of RC levels for cardiovascular disease health in the general population.

Habitual use of glucosamine and adverse liver outcomes among patients with type 2 diabetes and MASLD.

Glucosamine is a dietary supplement commonly used to support joint health. However, there has been interest in exploring other effects of glucosamine on health outcomes due to its ant-inflammation effect. This study compared the risks of major adverse liver outcomes (MALOs) between regular users and non-users of glucosamine among patients with type 2 diabetes and metabolic dysfunction associated steatotic liver disease (MASLD) using the data from a large prospective cohort study. Demographic, anthropometric, laboratory and medication prescription information among 18 753 patients with type 2 diabetes and MASLD was obtained from the UK Biobank. MASLD was identified based on hepatic steatosis defined by fatty liver index ≥60 plus the presence of any clues of metabolic dysregulation and cardio-metabolic risk factors, excluding patients with moderate to severe alcohol consumption. During a mean follow-up of 11.4 years, 826 incident MALOs events were recorded. Patients not regularly using glucosamine compared with patients using glucosamine showed a significantly higher risk of the composite MALOs (HR 1.36, 95% confidence interval [CI] 1.09-1.69) as well as most individual MALOs except for ascites. The multivariable-adjusted HRs of MALOs within 3, 5 and 10 years among non-users of glucosamine compared with regular users were 1.79 (95% CI .69-2.03), 1.88 (95% CI 1.21-2.54) and 1.32 (95% CI 1.05-1.72), respectively. Further subgroup analyses in participants with different baseline characteristics and sensitivity analyses excluding participants who regularly took any other supplements and participants who used self-reports to diagnose diabetes confirmed the findings. The present study indicated that habitual use of glucosamine was associated with a low risk of individual and composite MALOs among patients with type 2 diabetes and MASLD.

Joint association of diabetes mellitus and inflammation status with biological ageing acceleration and premature mortality

BackgroundWe aimed to investigate the associations of diabetes mellitus (DM) and C-reactive protein (CRP) with biological ageing acceleration and mortality risk. MethodsWe analyzed data from 41,634 adults with CRP and DM at baseline. Subjects were categorized into high CRP (>3 mg/L) and low CRP (≤3 mg/L) groups. The cross-sectional endpoints of the study were biological ageing indicators Klemera-Doubal method BioAge acceleration (KDMAccel) and Phenotypic age acceleration (PhenoAgeAccel), and the follow-up endpoints were all-cause mortality and cardiovascular mortality. ResultsIn adults with high CRP, compared with those without DM, PhenoAgeAccel increased by 1.66 years (95 % CI: 1.38–1.93), and 8.74 years (95 % CI: 8.25–9.22) in adults with prediabetes and DM, respectively (p for interaction <0.001). Using the CRPlow/non-DM group as a reference, adults in the CRPhigh/non-DM, CRPlow/DM, and CRPhigh/DM groups had significantly advanced biological ageing. Compared to adults without DM, low CRP, and no ageing acceleration, the multivariable-adjusted HRs (95%CIs) of all-cause and cardiovascular mortality in those with DM, CRP, and ageing acceleration were 3.22 (2.79–3.72), and 3.57 (2.81–4.54), respectively. ConclusionsThese findings suggest that the joint presence of low-grade inflammation and DM might be associated with higher odds of biological ageing acceleration and premature mortality.

The complexity of glucose time series is associated with short- and long-term mortality in critically ill adults: a multi-center, prospective, observational study.

The wealth of data taken from continuous glucose monitoring (CGM) remains to be fully used. We aimed to evaluate the relationship between a promising new CGM metric, complexity of glucose time series index (CGI), and mortality in critically ill patients. A total of 293 patients admitted to mixed medical/surgical intensive care units from 5 medical centers in Shanghai were prospectively included between May 2020 and November 2021. CGI was assessed using intermittently scanned CGM, with a median monitoring period of 12.0days. Outcome measures included short- and long-term mortality. During a median follow-up period of 1.7years, a total of 139 (47.4%) deaths were identified, of which 73 (24.9%) occurred within the first 30days after ICU admission, and 103 (35.2%) within 90days. The multivariable-adjusted HRs for 30-day mortality across ascending tertiles of CGI were 1.00 (reference), 0.68 (95% CI 0.38-1.22) and 0.36 (95% CI 0.19-0.70), respectively. For per 1-SD increase in CGI, the risk of 30-day mortality was decreased by 51% (HR 0.49, 95% CI 0.35-0.69). Further adjustment for HbA1c, mean glucose during hospitalization and glucose variability partially attenuated these associations, although the link between CGI and 30-day mortality remained significant (per 1-SD increase: HR 0.57, 95% CI 0.40-0.83). Similar results were observed when 90-day mortality was considered as the outcome. Furthermore, CGI was also significantly and independently associated with long-term mortality (per 1-SD increase: HR 0.77, 95% CI 0.61-0.97). In critically ill patients, CGI is significantly associated with short- and long-term mortality.

A natural language processing algorithm accurately classifies steatotic liver disease pathology to estimate the risk of cirrhosis.

Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction-associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by the free-text nature of pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score MASLD histology features. From the Mass General Brigham health care system electronic medical record, we identified all patients (1987-2021) with steatosis on index liver biopsy after excluding excess alcohol use and other etiologies of liver disease. An NLP algorithm was constructed in Python to detect steatosis, lobular inflammation, ballooning, and fibrosis stage from pathology free-text and manually validated in >1200 pathology reports. Patients were followed from the index biopsy to incident decompensated liver disease accounting for covariates. The NLP algorithm demonstrated positive and negative predictive values from 93.5% to 100% for all histologic concepts. Among 3134 patients with biopsy-confirmed MASLD followed for 20,604 person-years, rates of the composite endpoint increased monotonically with worsening index fibrosis stage (p for linear trend <0.005). Compared to simple steatosis (incidence rate, 15.06/1000 person-years), the multivariable-adjusted HRs for cirrhosis were 1.04 (0.72-1.5) for metabolic dysfunction-associated steatohepatitis (MASH)/F0, 1.19 (0.92-1.54) for MASH/F1, 1.89 (1.41-2.52) for MASH/F2, and 4.21 (3.26-5.43) for MASH/F3. The NLP algorithm accurately scores histological features of MASLD from pathology free-text. This algorithm enabled the construction of a large and high-quality MASLD cohort across a multihospital health care system and disclosed an accelerating risk for cirrhosis based on the index MASLD fibrosis stage.

Blood pressure status, trajectories and cardiovascular disease: the CoLaus|PsyCoLaus prospective study

BackgroundHigh blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Adequate treatment of high BP should reduce the risk of CVD, but this association has seldom been...

Beverage Consumption, Genetic Predisposition, and Risk of Cardiovascular Disease among Adults with Type 2 Diabetes.

The evidence regarding the relationship between different types of beverages and cardiovascular health in individuals with type 2 diabetes (T2D) is scarce. To prospectively examine the associations between individual beverage consumption, genetic predisposition, and risk of incident cardiovascular disease (CVD) among adults with T2D. We analyzed the associations of individual beverage intake with risks of CVD and ischemic heart disease (IHD) in 7315 participants with T2D, overall or stratified by genetic risk to CVD, using data from the UK Biobank study. During a median follow-up of 6.1 years, 878 incident CVD cases were identified, including 517 IHD cases. Higher intakes of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices were each linearly associated with a higher CVD (Pnonlinearity > 0.05). Comparing the highest to lowest groups of beverage consumption, the multivariable-adjusted HRs (95% CIs) of CVD were 1.54 (1.14, 2.07) for SSBs, 1.34 (1.07, 1.69) for ASBs, and 1.33 (1.01, 1.76) for natural juices. Similar results were observed for incident IHD. Moreover, no significant interactions between these beverages and the CVD genetic risk score were observed. Replacing half-unit/day of SSBs or natural juices with coffee, tea, or yogurt, but not ASBs, was associated with a 20%-46% lower risk of CVD and IHD. Higher intakes of SSBs, ASBs, and natural juices were each linearly associated with an increased risk of CVD among individuals with T2D, regardless of genetic predisposition. Our findings highlight the importance of selecting healthy beverage options to improve cardiovascular health in patients with T2D.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

The effect of marine omega-3 PUFAs on risk of stroke remains unclear. We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Diabetic retinopathy related homeostatic dysregulation and its association with mortality among diabetes patients: A cohort study from NHANES

AimsTo develop a metric termed the diabetic retinopathy-related homeostatic dysregulation (DRHD) value, and estimate its association with future risk of mortality in individuals with type 2 diabetes. MethodsWith the data of the NHANES, the biomarkers associated with DR were identified from 40 clinical parameters using LASSO regression. Subsequently, the DRHD value was constructed utilizing the Mahalanobis distance approach. In the retrospective cohortof 6420 type 2 diabetes patients, we estimated the associations between DRHD values and mortality related to all-cause, cardiovascular disease (CVD) and diabetes-specific causes using Cox proportional hazards regression models. ResultsA set of 14 biomarkers associated with DR was identified for the construction of DRHD value. During an average of 8 years of follow-up, the multivariable-adjusted HRs and corresponding 95 % CIs for the highest quartiles of DRHD values were 2.04 (1.76, 2.37), 2.32 (1.78, 3.01), and 2.29 (1.72, 3.04) for all-cause, CVD and diabetes-specific mortality, respectively. Furthermore, we developed a web-based calculator for the DRHD value to enhance its accessibility and usability (https://dzwxl-drhd.streamlit.app/). ConclusionsOur study constructed the DRHD value as a measure to assess homeostatic dysregulation among individuals with type 2 diabetes. The DRHD values exhibited potential as a prognostic indicator for retinopathy and for mortality in patients affected by type 2 diabetes.

Gut microbiota-bile acid axis mediated the beneficial associations between dietary lignans and hyperuricemia: a prospective study.

Background: The escalating prevalence of hyperuricemia is emerging as a significant public health concern. The association between dietary lignans and hyperuricemia is yet to be fully elucidated. Our study aims to evaluate the relationships between dietary lignan intake and hyperuricemia among middle-aged and elderly Chinese individuals, with an additional focus on investigating the underlying mechanisms. Methods: Dietary lignan intake was measured using a validated Food Frequency Questionnaire in 3801 participants at the baseline. Among them, 2552 participants were included in the longitudinal study with a median follow-up of 10.5 years. The gut microbiota was analyzed by shotgun metagenome sequencing in 1789 participants, and the targeted fecal metabolome was determined in 987 participants using UPLC-MS/MS at the midpoint of follow-up. Results: The multivariable-adjusted HRs (95% CIs) for hyperuricemia incidence in the highest quartile (vs. the lowest quartile) of dietary intake of total lignans, matairesinol, pinoresinol, and secoisolariciresinol were 0.93 (0.78-1.10), 0.77 (0.66-0.90), 0.83 (0.70-0.97), and 0.85 (0.73-1.00), respectively. The gut microbial and fecal metabolic compositions were significantly different across the dietary lignan groups and the hyperuricemia groups. The beneficial associations between dietary lignans and hyperuricemia might be mediated by several gut microbes (e.g., Fusobacterium mortiferum and Blautia sp. CAG-257) and the downstream bile acid products (e.g., NorCA, glycochenodeoxycholic acid, and glycoursodeoxycholic acid). Conclusion: We found that dietary lignans were inversely associated with hyperuricemia incidence, and the gut microbiota-bile acid axis might mediate this association. Our findings provide new perspectives on precise therapeutic targets and underlying mechanisms for conditions associated with elevated uric acid.

Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse LimbEvents.

Lp(a) (lipoprotein[a])-lowering therapy to reduce cardiovascular disease is under investigation in phase 3 clinical trials. High Lp(a) may be implicated in peripheral artery disease (PAD), abdominal aortic aneurysms (AAAs), and major adverse limb events (MALE). The authors investigated the association of high Lp(a) levels and corresponding LPA genotypes with risk of PAD, AAA, and MALE. The authors included 108,146 individuals from the Copenhagen General Population Study. During follow-up, 2,450 developed PAD, and 1,251 AAAs. Risk of MALE was assessed in individuals with PAD at baseline and replicated in the Copenhagen City Heart Study. Higher Lp(a) was associated with a stepwise increase in risk of PAD and AAA (P for trend<0.001). For individuals with Lp(a) levels≥99th (≥143mg/dL, ≥307nmol/L) vs<50th percentile (≤9mg/dL,≤17nmol/L), multivariable-adjusted HRs were 2.99 (95%CI: 2.09-4.30) for PAD and 2.22 (95%CI: 1.21-4.07) for AAA. For individuals with PAD, the corresponding incidence rate ratio for MALE was 3.04 (95%CI: 1.55-5.98). Per 50mg/dL (105nmol/L) genetically higher Lp(a) risk ratios were 1.39 (95%CI: 1.24-1.56) for PAD and 1.21 (95%CI: 1.01-1.44) for AAA, consistent with observational risk ratios of 1.33 (95%CI: 1.24-1.43) and 1.27 (95%CI: 1.15-1.41), respectively. In women smokers aged 70 to 79 years with Lp(a)<50th and≥99th percentile, absolute 10-year risks of PAD were 8% and 21%, and equivalent risks in men 11% and 29%, respectively. For AAA, corresponding risks were 2% and 4% in women, and 5% and 12% in men. High Lp(a) levels increased risk of PAD, AAA, and MALE by 2- to 3-fold in the general population, opening opportunities for prevention given future Lp(a)-lowering therapies.

Serum osmolality was non-linearly associated with the risk of all-cause and cardiovascular mortality in patients with diabetes

AimsThis study aimed to evaluate the relationship between both low and high osmolarity and the risk of all-cause and cause-specific mortality in diabetic population.MethodsAll participants were included from the National...

Serum 25-hydroxyvitamin D, type 2 diabetes, and liver-related outcomes: Secondary data analysis of a prospective recruited cohort.

The association of vitamin D deficiency, which is prevalent in type 2 diabetes mellitus (T2DM), with liver disease and related mortality has not been quantified. Our study aimed to (1) investigate whether there is a synergistic association of vitamin D deficiency and T2DM with liver-related outcomes and (2) explore whether high 25-hydroxyvitamin D [25(OH)D] concentrations are associated with a lower risk of liver-related outcomes in T2DM. Leveraging the data from UK Biobank, we conducted 2 studies: study I assessed the joint associations of vitamin D deficiency [25(OH)D <50nmol/L] and T2DM with liver-related outcomes among 439,276 participants, and study II explored the associations of vitamin D status with liver-related outcomes among 21,519 individuals with T2DM. Baseline T2DM was identified through medication, laboratory test, and electronic health-related records. Serum 25(OH)D was measured by direct competitive chemiluminescent immunoassay. Liver-related outcomes included 6 liver disease end points and mortality by overall liver disease, chronic liver disease, and severe liver disease. During an average follow-up duration of 11.6 years, we observed a significant positive additive interaction effect (all synergy index>1.0) of T2DM and vitamin D deficiency on the risk of liver-related outcomes. Compared with participants without either T2DM or vitamin D deficiency, the multivariable-adjusted HRs of overall liver diseases were 1.29 for participants without T2DM but with vitamin D deficiency, 1.73 for participants with T2DM but without vitamin D deficiency, and 2.19 for participants with both T2DM and vitamin D deficiency. In individuals with T2DM, we observed that participants without vitamin D deficiency were inversely associated with incident liver disease and related mortality (multivariable-adjusted HRs 0.41-0.81) when compared with individuals with vitamin D deficiency. There are positive synergistic associations of vitamin D deficiency and T2DM with liver-related outcomes. Inverse associations between serum 25(OH)D concentrations and liver-related outcomes were observed in individuals with T2DM.

Age at Onset of Heart Failure and Subsequent Risk of Dementia: A Longitudinal Cohort Study

BackgroundThe average age at onset of heart failure (HF) shows a progressive decrease in recent years; however, the association between age at onset of HF and risk of subsequent dementia remains undetermined. ObjectivesThis study sought to examine whether younger onset age of HF is associated with a higher risk of incident dementia. MethodsIndividual-level data from the UK Biobank cohort study were analyzed in the present study. Cox regression models and the propensity score matching method were used to analyze the associations of HF and its onset age with subsequent all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD). ResultsCompared with 442,791 participants without HF, those with HF had a higher risk of all-cause dementia (HR: 1.14). Among 14,413 participants with HF, multivariable-adjusted HRs for all-cause dementia, AD, and VD were 1.18, 1.64, and 1.27, respectively, per 10-year decrease in age at HF onset. The propensity score matching analyses found that the strength of association between HF and all-cause dementia increased with decreasing onset age of HF (≥75 years, HR: 1.05; 65-74 years, HR: 1.10; <65 years, HR: 1.67) after multivariable adjustment. Similarly, participants with onset age of HF <65 years had the greatest HRs for incident AD and VD, compared with their matched control subjects. ConclusionsYounger age at HF onset was associated with increased risk of dementia. Individuals with an onset age of HF before 65 years of age may represent a particularly vulnerable population for dementia irrespective of subtypes and need careful monitoring and timely intervention to attenuate subsequent risk of incident dementia.

Lipoprotein(a): A Residual Cardiovascular Risk Factor in Statin-Treated Stroke Survivors: Insights From the SPARCL Trial

BackgroundIn the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol levels) trial, atorvastatin (80 mg/d) was compared to placebo in patients with recent stroke or transient ischemic attack (TIA) and no known coronary artery disease. ObjectivesThis study aimed to assess the contribution of lipoprotein(a) [Lp(a)] to subsequent cerebrovascular and cardiovascular events in stroke/TIA survivors. MethodsLp(a) levels and apolipoprotein(a) [apo(a)] isoform size were determined by liquid-chromatography mass spectrometry in samples collected at baseline from 2,814 SPARCL participants (1,418 randomized to atorvastatin and 1,396 to placebo). Within each treatment arm, patients in the highest quartile (≥84.0 nmol/L) were compared with those in the lowest quartiles of Lp(a) concentrations. Patients in the lowest quartile (≤25.9 Kringle IV domains) of apo(a) isoform sizes were compared with those in the highest quartiles. Multivariable-adjusted HRs were calculated using Cox proportional regression models. ResultsThere was no significant association between Lp(a) concentrations or apo(a) isoform sizes and the risk of recurrent stroke, the primary outcome of SPARCL, or cerebrovascular events in patients randomized to atorvastatin or placebo. In contrast, in patients randomized to atorvastatin, elevated Lp(a) concentrations and short apo(a) isoforms were positively and independently associated with an increased risk of coronary events (HR: 1.607 [95% CI: 1.007-2.563] and HR: 2.052 [95% CI: 1.303-3.232]). No such association was found in patients randomized to placebo (HR: 1.025 [95% CI: 0.675-1.555] and HR: 1.097 [95% CI: 0.735-1.637]). ConclusionsLp(a) contributes to the residual coronary artery disease risk of statin-treated stroke/TIA survivors, paving the way for use of therapies targeting Lp(a) in this population with stroke. (Lipitor In The Prevention Of Stroke, For Patients Who Have Had A Previous Stroke [SPARCL]; NCT00147602)

Sleep duration trajectories and all-cause mortality among Chinese elderly: A community-based cohort study

BackgroundChina is among the largest and fastest aging countries. The elderly population is more vulnerable, with higher proportion of inappropriate sleep duration and risk of mortality, compared with young and middle-aged adults. Single-measured sleep duration has been associated with mortality, but the health effects of long-term sleep duration trajectories remain unknown. This study aimed to explore the prospective associations between sleep duration trajectories and all-cause mortality among Chinese elderly.MethodsParticipants (n = 3,895; median age: 82 years; females: 53.3%) who reported sleep duration in all three surveys (2005, 2008, and 2011) from the community-based Chinese Longitudinal Healthy Longevity Survey (CLHLS) were followed up until 2019 (about 8 years). We identified sleep duration trajectories by latent class mixed model and explored their association with all-cause mortality using Cox hazard proportional regression and Laplace regression models. Further, stratified analysis by demographic characteristics and lifestyles and sensitivity analysis by lag effect, health-related factors, and inverse probability weighting were used to verify the robustness of the association. In addition, we explored the threshold effect of baseline sleep duration on the risk of all-cause mortality.ResultsWe documented 1,881 all-cause deaths during 16,689 person-years of follow-up. Five sleep duration trajectories were identified: moderately increased trajectory (28.1%), rapidly increased trajectory (7.2%), persistent sleep trajectory of 7 h (33.7%), moderately decreased trajectory (21.3%), and rapidly decreased trajectory (9.7%). Compared with the persistent sleep trajectory of 7 h, the multivariable-adjusted HRs (95%CI) for moderately increased trajectory, rapidly increased trajectory, moderately decreased trajectory, and rapidly decreased trajectory were 1.21 (1.08, 1.36), 1.21 (1.01, 1.44), 0.95 (0.82, 1.10), and 0.93 (0.78, 1.11), respectively; and the corresponding difference in median survival time (95%CI) were -0.53 (-1.01, -0.05), -0.43 (0.16, -1.02), 0.26 (-0.34, 0.86), and 0.25 (-0.51, 1.02), respectively. Stratified and sensitivity analyses showed consistent results. Threshold analysis indicated a sharply increased risk of mortality in participants whose sleep exceeds 9 h (HR = 1.20, 95%CI: 1.11, 1.30).ConclusionCompared with the persistent sleep trajectory of 7 h, moderately and rapidly increased sleep duration trajectories were associated with higher subsequent mortality in Chinese elderly. Those who report sleep exceeding 9 h may be at high risk for all-cause mortality.

Nonalcoholic fatty liver disease and risk of incident young-onset hypertension: Effect modification by sex

Background and aimsAlthough nonalcoholic fatty liver disease (NAFLD) and hypertension are increasingly common among young adults, it is uncertain if NAFLD affects incidence of young-onset hypertension, and if the association is modified by sex. We investigated potential effect modification by sex on the association between NAFLD and incident hypertension in young adults (<40 years). Method and resultsThis cohort study comprised 85,789 women and 67,553 men aged <40 years without hypertension at baseline. Hepatic steatosis was assessed by liver ultrasound and classified as mild or moderate/severe. Hypertension was defined as blood pressure (BP) ≥130/80 mmHg; self-reported history of physician-diagnosed hypertension; or current use of BP-lowering medications. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident hypertension by NAFLD status (median follow-up 4.5 years). A total of 25,891 participants developed incident hypertension (incidence rates per 103 person-years: 15.6 for women and 63.5 for men). Multivariable-adjusted HRs (95% CIs) for incident hypertension comparing no NAFLD (reference) with mild or moderate/severe NAFLD were 1.68 (1.56–1.80) and 1.83 (1.60–2.09) for women and 1.21 (1.17–1.25) and 1.23 (1.17–1.30) for men, respectively. Stronger associations were consistently observed between NAFLD and incident hypertension in women, regardless of obesity/central obesity (all p-values for interaction by sex <0.001). ConclusionsNAFLD is a potential risk factor for young-onset hypertension with a relatively greater impact in women and in those with more severe hepatic steatosis.