Association of cardiovascular health metrics with all-cause and cardiovascular disease mortality in chronic kidney disease: A cohort study.

BACKGROUND AND AIMS: Since the global burden of chronic kidney disease (CKD) is rising rapidly, the study aimed to assess the association of cardiovascular health (CVH) metrics with all-cause and cardiovascular disease (CVD) mortality among individuals with CKD. METHODS AND RESULTS: The cohort study included 5834 participants with CKD from the National Health and Nutrition Examination Survey 1999-2018. A composite CVH score was calculated based on smoking status, physical activity, body mass index, blood pressure, total cholesterol, diet quality, and glucose control. Primary outcomes were all-cause and CVD mortality as of December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between CVH metrics and deaths in CKD patients. During a median follow-up of 7.2 years, 2178 all-cause deaths and 779 CVD deaths were documented. Compared to participants with ideal CVH, individuals with intermediate CVH exhibited a 46.0% increase in all-cause mortality (hazard ratio, 1.46; 95% confidence interval: 1.17, 1.83), while those with poor CVH demonstrated a 101.0% increase (2.01; 1.54, 2.62). For CVD mortality, individuals with intermediate CVH experienced a 56.0% increase (1.56; 1.02, 2.39), and those with poor CVH demonstrated a 143.0% increase (2.43; 1.51, 3.91). Linear trends were noted for the associations of CVH with both all-cause mortality (P for trend <0.001) and CVD mortality (P for trend = 0.02). CONCLUSIONS: Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD, which highlights the importance of maintaining good CVH in CKD patients.

Cognitive-behavioral therapy for patients with somatoform disorders: A pilot preliminary randomized controlled trial.

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

Associations of combined healthy lifestyles with cancer morbidity and mortality among individuals with diabetes: results from five cohort studies in the USA, the UK and China.

AIMS/HYPOTHESIS: Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes. METHODS: We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors. RESULTS: During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups. CONCLUSIONS/INTERPRETATION: This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.

Overall lifestyles and socioeconomic inequity in mortality and life expectancy in China: the China health and nutrition survey.

BACKGROUND: socioeconomic inequity in mortality and life expectancy remains inconclusive in low- and middle-income countries, and to what extent the associations are mediated or modified by lifestyles remains debatable. METHODS: we included 21,133 adults from China Health and Nutrition Survey (1991-2011) and constructed three parameters to reflect participants' overall individual- (synthesising income, education and occupation) and area-level (urbanisation index) socioeconomic status (SES) and lifestyles (counting the number of smoking, physical inactivity and unhealthy diet and bodyweight). HRs for mortality and life expectancy were estimated by time-dependent Cox model and life table method, respectively. RESULTS: during a median follow-up of 15.2 years, 1,352 deaths were recorded. HRs (95% CIs) for mortality comparing low versus high individual- and area-level SES were 2.38 (1.75-3.24) and 1.84 (1.51-2.24), respectively, corresponding to 5.7 (2.7-8.6) and 5.0 (3.6-6.3) life-year lost at age 50. Lifestyles explained ≤11.5% of socioeconomic disparity in mortality. Higher lifestyle risk scores were associated with higher mortality across all socioeconomic groups. HR (95% CI) for mortality comparing adults with low individual-level SES and 3-4 lifestyle risk factors versus those with high SES and 0-1 lifestyle risk factors was 7.06 (3.47-14.36), corresponding to 19.1 (2.6-35.7) life-year lost at age 50. CONCLUSION: this is the first nationwide cohort study reporting that disadvantaged SES was associated with higher mortality and shorter life expectancy in China, which was slightly mediated by lifestyles. Risk lifestyles were related to higher mortality across all socioeconomic groups, and those with risk lifestyles and disadvantaged SES had much higher mortality risks.

Screening high-risk population of persistent postpartum hypertension in women with preeclampsia using latent class cluster analysis.

BACKGROUND: A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This study aimed to screen patients with PE to identify the high-risk population with persistent PHTN. METHODS: This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN. RESULTS: The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92-8.27) and three times (OR, 2.931; 95% CI, 1.91-4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups. CONCLUSION: Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study's findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease.

Association of sugar-sweetened beverage and artificially sweetened beverage intakes with mortality: an analysis of US National Health and Nutrition Examination Survey.

PURPOSE: Current evidence on the associations between sugar-sweetened beverage (SSB) intakes and mortality is inconsistent, whereas the evidence on artificially sweetened beverages (ASBs) was sparse. We aimed to investigate the associations of SSB and ASB intakes with mortality in a nationally representative sample of US adults. METHODS: Participants from the National Health and Nutrition Examination Survey (NHANES, 1999-2014; n = 31,402) were linked to the US mortality registry by the end of 2015. SSB and ASB intakes were collected using 24-h dietary recalls. Cox proportional hazard regression models were used to assess the associations of intakes of SSBs, ASBs, and added sugar from SSBs with mortality with adjustment for demographic, lifestyle, comorbidity, and dietary factors. RESULTS: After a mean follow-up of 7.9 years, 3878 deaths were identified. The multivariate-adjusted hazard ratios (95% confidence intervals) associated with each additional serving/d of SSB were 1.05 (1.01-1.09) for all-cause mortality and 1.11 (1.03-1.21) for heart disease mortality. Hazard ratios (95% confidence intervals) comparing the extreme quintiles of added sugar intakes from SSBs were 1.22 (1.05-1.42) for all-cause mortality and 1.45 (1.06-1.97) for heart disease mortality. No significant relationship was found between SSB intakes and cancer mortality or between high ASB intakes and mortality. Substituting one serving/d of SSB by an equivalent amount of ASBs, unsweetened coffees and teas, and plain water was associated with a 4-7% lower risk of all-cause mortality. CONCLUSION: Higher SSB intakes were associated with higher risks of all-cause mortality and heart disease mortality. High ASB intakes were not significantly associated with mortality. ASBs, unsweetened coffees and teas, and plain water might be optional alternatives for reducing SSB intakes.

Modular prosthesis fracture in a patient with developmental dysplasia of the hip: a case report and literature review.

BACKGROUND: Modular prosthesis fracture, especially distal femoral fracture, is a rare complication of total hip arthroplasty (THA). However, it is catastrophic, and may have a serious impact on the patients. A distal femoral prosthesis fracture in a patient with developmental dysplasia of the hip (DDH) with nonunion at the subtrochanteric osteotomy site has not yet been reported in any literature. This report presents the first such case, with a purpose of analyzing the causes of modular prosthesis fractures and nonunion of the osteotomy area, so as to provide orthopedic surgeons with experience and lessons. CASE PRESENTATION: We report the case of a 52-year-old woman with the distal femoral prosthesis fracture after THA and subtrochanteric osteotomy for Crowe type IV DDH. The patient had severe pain in the left thigh and her activities were limited. Plain radiographs revealed fracture of the left distal femoral prosthesis and nonunion in the subtrochanteric osteotomy region of the left femur. After a revision of the THA, the patient's symptoms were resolved. CONCLUSIONS: A prosthesis fracture combined with nonunion at the subtrochanteric osteotomy site is a rare complication. Modular THA combined with a subtrochanteric osteotomy in the treatment of Crowe type IV DDH should reduce the damage to blood supply and avoid further nonunion of the osteotomy area, which may otherwise lead to modular prosthesis fractures. A detailed preoperative plan and suitable rehabilitation program may help minimize the occurrence of subtrochanteric osteotomy nonunion and reduce complications, including femoral prosthesis fractures, in patients with DDH.

Combined lifestyle factors, incident cancer, and cancer mortality: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Cancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality. METHODS: EMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted. RESULTS: The HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66-0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42-0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses. CONCLUSIONS: Adopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention.

Chemical constituents from the thorns of Gleditsia sinensis and their cytotoxic activities.

A new aromatic glycoside (1) and a new natural product, neolignan (2), along with twenty-three known compounds (3-25), were isolated from the thorns of Gleditsia sinensis. According to the spectroscopic analyses (IR, UV, HRESIMS, NMR and ECD), the structures of isolates were elucidated. Herein, compounds 4, 6-8, 10-13, 15, 16, 18, 20, 23 were isolated from the plant of G. sinensis for the first time. Moreover, compounds 4, 6, 15 and 24 showed cytotoxic effects on human ovarian cancer (SKOV-3) cells with IC50 values of 24.83 ± 4.90, 48.86 ± 9.11, 80.13 ± 5.62, 15.38 ± 2.21 µM, respectively. [Formula: see text].

Synthesis, Crystal Structures and Luminescence Properties of Three New Cadmium 3D Coordination Polymers.

: The new rigid planar ligand 2,5-bis(3-(pyridine-4-yl)phenyl)thiazolo[5,4-d]thiazole (BPPT) has been synthesized, which is an excellent building block for assembling coordination polymer. Under solvothermal reaction conditions, cadmium ion with BPPT in the presence of various carboxylic acids including (1,1'-biphenyl)-4,4'-dicarboxylic acid (BPDC), isophthalic acid (IP), and benzene-1,3,5-tricarboxylic acid (BTC) gave rise to three coordination complexes, viz, [Cd(BPPT)(BPDA)](BPPT)n (1), [Cd(BPPT) (IP)] (CH3OH) (2), and [Cd3(BPPT)3(BTC)2(H2O)2] (3). The structures of 1, 2, and 3 were characterized by single crystal X-ray diffraction. The IR spectra as well as thermogravimetric and luminescence properties were also investigated. Complex 1 is a two-dimensional (2D) network and further stretched to a 3D supramolecular structure through π-π stacking interaction. The complexes 2 and 3 show 3D framework. The complexes 1, 2, and 3 exhibited luminescence property at room temperature.

Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis.

PURPOSE: We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality. METHODS: We searched PubMed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events [including total CVD, CVD mortality, total coronary heart disease (CHD), fatal CHD, nonfatal myocardial infarction (MI), and stroke] and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis. RESULTS: Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I2 = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I2 = 32.1%; two studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality, or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I2 = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I2 = 0%; two studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD. CONCLUSIONS: Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.

Quality and safety control of tumor-shrinking decoction (TSD): A Chinese herbal preparation for the treatment of uterine fibroids.

Reproducible efficacy assessments of Chinese herbal medicines are largely based on well-established quality control procedures. This study presents a comprehensive quality control procedure for tumor-shrinking decoction (TSD), a 15-herb preparation under study as a potential therapy for uterine fibroids. Morphological, microscopic, and physicochemical authentications were first carried out on individual herbal medicines composing TSD. Contaminant tests on TSD for the presence of heavy metals and pesticide residues were performed by atomic absorption spectrophotometry and gas chromatography-mass spectrometry analysis. Furthermore, batch-to-batch quality monitoring of the decoction was investigated via ultra-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC). An aqueous extract of the herbal medicines was prepared and formulated into TSD. The tested contaminants were within the maximum permitted levels of the Hong Kong government in proprietary Chinese medicines. UPLC and HPLC fingerprints for quality tracking on TSD were established. The decoction was quantitatively standardized by UPLC and HPLC, respectively, with five and three chemical compounds serving as references. Collectively, the procedure established in this study will not only serve as a fundamental basis for the investigation and development of TSD as a novel therapy for uterine fibroids, but also as a protocol for studying other polycomponent herbal preparations.

Evaluation of Vitamin C Supplementation on Kidney Function and Vascular Reactivity Following Renal Ischemic Injury in Mice.

BACKGROUND/AIMS: Renal ischemia/reperfusion injury (IRI) is a very common clinical event and usually leads to ischemic acute renal failure (ARF). In the present study, we investigated the protective role of vitamin C in renal function and renal arterial relaxation following ischemic injury. METHODS: IRI model in mice was used. Various biochemical parameters including nitric oxide (NO), reduced glutathione (GSH), total reactive oxygen species (ROS) level and superoxide dismutase (SOD) were examined. Doppler was used to investigate renal arterial resistance. The isolated renal arterial rings served for hypoxia/reoxygenation analysis. Acetylcholine (ACh) and sodium nitroprusside (SNP)-induced relaxations of isolated renal arterial rings were exerted. RESULTS: Vitamin C supplementation preserved kidney morphology and renal function following IRI. It was shown that pretreatment with vitamin C for mice subjected to IRI significantly elevated renal NO and GSH levels after reperfusion. Meanwhile, vitamin C administration decreased resistance index of renal artery and ameliorated oxidative stress secondary to IRI. The total ROS level in renal artery was decreased whereas the renal arterial SOD expression was increased by vitamin C supplementation following IRI. Pretreatment with vitamin C significantly potentiated the ACh and SNP-induced relaxations in both control and hypoxic renal arterial rings. CONCLUSION: Vitamin C protects kidney function and renal arterial reactivity against IRI. The protective role of vitamin C is linked to ROS, SOD, GSH and NO levels in renal ischemic injury.

The effects of CoCl2 on HIF-1α protein under experimental conditions of autoprogressive hypoxia using mouse models.

It is well known that cobalt chloride (CoCl2) can enhance the stability of hypoxia-inducible factor (HIF)-1α. The aim of this study is to detect the effect of CoCl2 on the hypoxia tolerance of mice which were repeatedly exposed to autoprogressive hypoxia. Balb/c mice were randomly divided into groups of chemical pretreatment and normal saline (NS), respectively injected with CoCl2 and NS 3 h before exposure to hypoxia for 0 run (H0), 1 run (H1), and 4 runs (H4). Western Blot, electrophoretic mobility shift assay (EMSA), extracellular recordings population spikes in area cornus ammonis I (CA 1) of mouse hippocampal slices and real-time were used in this study. Our results demonstrated that the tolerance of mice to hypoxia, the changes of HIF-1α protein level and HIF-1 DNA binding activity in mice hippocampus, the mRNA level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the disappearance time of population spikes of hippocampal slices were substantially different between the control group and the CoCl2 group. Over-induction of HIF-1α by pretreatment with CoCl2 before hypoxia did not increase the hypoxia tolerance.

Circulating metabolic biomarkers and risk of new-onset hypertension: findings from the UK Biobank.

OBJECTIVE: The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. METHODS: We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. CONCLUSION: Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.

Nonlinear relationship between high-density lipoprotein cholesterol and cardiovascular disease: an observational and Mendelian randomization analysis.

BACKGROUND: Clinical trials and Mendelian randomization (MR) studies reported null effects of high-density lipoprotein cholesterol (HDL-C) on risk of cardiovascular disease (CVD), which might have overlooked a nonlinear causal association. We aimed to investigate the dose-response relationship between circulating HDL-C concentrations and CVD in observational and MR frameworks. METHODS: We included 348,636 participants (52,919 CVD cases and 295,717 non-cases) of European ancestry with genetic data from the UK Biobank (UKB) and acquired genome-wide association summary data for HDL-C of Europeans from the Global Lipids Genetics Consortium (GLGC). Observational analyses were conducted in the UKB. Stratified MR analyses were conducted combing genetic data for CVD from UKB and lipids from GLGC. RESULTS: Observational analyses showed L-shaped associations of HDL-C with CVD, with no further risk reduction when HDL-C levels exceeded 70 mg/dL. Multivariable MR analyses across entire distribution of HDL-C found no association of HDL-C with CVD, after control of the pleiotropic effect on other lipids and unmeasured pleiotropism. However, in stratified MR analyses, significant inverse associations of HDL-C with CVD were observed in the stratum of participants with HDL-C ≤ 50 mg/dL (odds ratio per unit increase, 0.86; 95 % confidence interval, 0.79-0.94), while null associations were observed in any stratum above 50 mg/dL. CONCLUSIONS: Our data suggest a potentially causal inverse association of HDL-C at low levels with CVD risks. These findings advance our knowledge about the role of HDL as a potential target in CVD prevention and therapy.

Association of ultraprocessed food consumption with risk of microvascular complications among individuals with type 2 diabetes in the UK Biobank: a prospective cohort study.

BACKGROUND: The poor nutritional characteristics and potentially harmful molecules in ultraprocessed foods (UPFs) are risk factors for diabetic microvascular complications. However, the evidence regarding UPFs and diabetic microvascular complications remains limited. OBJECTIVES: We aimed to evaluate the associations between UPF consumption and risk of diabetic microvascular complications, to examine the underlying biological pathways (e.g., inflammation and lipid profile), and to identify whether the associations differ by type of UPF dietary patterns. METHODS: We included a prospective cohort of UK Biobank participants with type 2 diabetes (T2D) having at least one 24-h dietary recall (N = 5685). UPFs were defined using the Nova classification. Principal component analysis was used to derive UPF consumption patterns. Associations of UPFs and their consumption patterns with microvascular complications were assessed using Cox proportional hazards regression models. Mediation analyses were used to estimate the mediating effects of 22 biomarkers. RESULTS: During a median of 12.7 y of follow-up, 1243 composite microvascular complications events occurred (599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events). Five consumption patterns were identified (spread and bread, cereal prepared with liquids, dairy-based products, sugary beverage and snack, and mixed beverage and savory snack patterns). A 10% increment in the proportion of UPF was associated with higher hazards of the composite microvascular complications (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.03, 1.13) and diabetic kidney disease (HR: 1.13; 95% CI: 1.06, 1.20). Triglycerides, C-reactive protein, and body mass index collectively explained 22.0% (9.6%-43.0%) of the association between UPF intake and composite microvascular complications. Pattern high in mixed beverage and savory snack was associated with a higher risk of composite microvascular complications. CONCLUSIONS: Higher UPF consumption was associated with higher risks of diabetic microvascular complications, and the association was partly mediated through multiple potential ways.

Socioeconomic status, lifestyle and risk of incident dementia: a prospective cohort study of 276730 participants.

Healthy lifestyle might alleviate the socioeconomic inequities in health, but the extent of the joint and interactive effects of these two factors on dementia are unclear. This study aimed to detect the joint and interactive associations of socioeconomic status (SES) and lifestyle factors with incident dementia risk, and the underlying brain imaging alterations. Cox proportional hazards analysis was performed to test the joint and interactive associations. Partial correlation analysis was performed to reflect the brain imaging alterations. A total of 276,730 participants with a mean age of 55.9 (±8.0) years old from UK biobank were included. Over 8.5 (±2.6) years of follow-up, 3013 participants were diagnosed with dementia. Participants with high SES and most healthy lifestyle had a significantly lower risk of incident dementia (HR=0.19, 95% CI=0.14 to 0.26, P<2×10-16), Alzheimer's disease (AD, HR=0.19, 95% CI=0.13 to 0.29, P=8.94×10-15), and vascular dementia (HR=0.24, 95% CI=0.12 to 0.48, P=7.57×10-05) compared with participants with low SES and an unhealthy lifestyle. Significant interactions were found between SES and lifestyle on dementia (P=0.002) and AD (P=0.001) risks; the association between lifestyle and dementia was stronger among those of high SES. The combination of high SES and healthy lifestyle was positively associated with higher volumes in brain regions vulnerable to dementia-related atrophy. These findings suggest that SES and lifestyle significantly interact and influence dementia with its related brain structure phenotypes.