Dose–response relationship between distinct serum uric acid trajectories and metabolic syndrome risk: A 5-year prospective cohort study

Background and aimsAlthough high serum uric acid (SUA) at baseline has been linked to increased risk for metabolic syndrome (MetS), the association of longitudinal SUA changes with MetS risk is unclear. We aimed to examine the effect of distinct SUA trajectories on new-onset MetS risk by sex in a Chinese cohort.Methods and resultsA total of 2364 women and 2770 men who were free of MetS in 2013 were enrolled in this study and followed up to 2018. Group-based trajectory modeling was applied to identify SUA trajectories. Cox proportional hazards model was used to evaluate the association between SUA trajectory and new-onset MetS. The dose–response relationship between SUA trajectories and MetS risk was examined by treating trajectory groups as a continuous variable. During a median follow-up of 48.0 months, 311 (13.16%) women and 950 (34.30%) men developed MetS. SUA trajectories (2013–2018) were defined as four distinct patterns in both women and men: “low”, “moderate”, “moderate-high”, and “high”. Compared with “low” SUA trajectory, the adjusted hazard ratio for incident MetS among participants with “moderate”, “moderate-high” and “high” trajectory was in a dose–response manner: 1.75 (95% CI: 1.08–2.82), 1.94 (95% CI: 1.20–3.14), and 3.05 (95% CI: 1.81–5.13), respectively, for women; 1.20 (95% CI: 0.97–1.49), 1.48 (95% CI: 1.19–1.85), and 1.66 (95% CI: 1.25–2.21), respectively, for men.ConclusionsElevated SUA trajectories are associated with increased risk for new-onset MetS in women and men. Monitoring SUA trajectories may assist in identifying subpopulations at higher risk for MetS.     

Serum uric acid is associated with incident metabolic syndrome independent of body shape index and body roundness index in healthy individuals

Background and aimsElevated serum uric acid (SUA) levels, body shape index (BSI) and body roundness index (BRI) were associated with incident metabolic syndrome (MetS). We aimed to investigate the relationship among the SUA level, BSI, and BRI on the incidence of MetS.Methods and resultsWe retrospectively included 6221 healthy individuals from annual health exams at our hospital between 2016/1/1 and 2016/12/31. We defined hyperuricemia as SUA levels greater than 7 mg/dl in men and 6 mg/dl in women and MetS according to the contemporary definition. The study cohort included 6221 healthy individuals with an overall incidence rate of MetS of 9.8%. Compared with the normouricemic group, the hyperuricemic group had a greater incidence of MetS (17.2% vs. 9.6%, P < 0.001). After full adjustment for confounders, the SUA level was significantly associated with incident MetS in addition to body mass index (BMI) (adjusted OR [aOR]: 1.161, 95% CI: 1.071–1.259, P < 0.001), BRI (aOR: 1.196, 95% CI: 1.104–1.296, P < 0.001), and BSI (aOR: 1.297, 95% CI: 1.200–1.403, P < 0.001). Regarding the anthropometric indices, BMI and BRI were independent predictors of incident MetS, but the BSI lost its significant association in multivariate logistic regression analyses. In sensitivity analyses, various thresholds of elevated SUA levels remained associated with incident MetS.ConclusionWe showed a dose-response effect of SUA on incident MetS independent of BMI, BRI and BSI in healthy individuals. Future studies can use SUA levels to stratify cardiometabolic risk in healthy individuals.Clinical trialsClinicalTrials.gov with the identification number NCT03473951.     

Association between PNPLA3 rs738409 variant and 5-year estimated glomerular filtration rate decline in post-menopausal women with type 2 diabetes: A panel-data analysis

Background and aimsLittle is known about the relationship between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 variant and decline in estimated glomerular filtration rate (eGFR) over time in individuals with type 2 diabetes (T2DM).Methods and resultsWe enrolled an outpatient sample of 46 post-menopausal women with T2DM and preserved kidney function at baseline (in 2017), who were followed through 2022. eGFR and albuminuria were measured annually. Genotyping of PNPLA3 rs738409 was performed by TaqMan-based RT-PCR system. Overall, 25 (54.3%) patients had PNPLA3 rs738409 CC (homozygous wild-type) genotype and 21 had CG or GG genotypes. During the 5-year follow-up, the presence of rs738409 CG/GG genotypes was associated with faster eGFR decline (coefficient: −6.55; 95% CI −11.0 to −2.08; p = 0.004 by random-effects panel data analysis). This association remained significant even after adjustment for 5-year changes in age, hemoglobin A1c, hypertension status, albuminuria and use of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists.ConclusionsThis pilot study suggests that in post-menopausal T2DM women with preserved kidney function at baseline, the risk allele (G) of PNPLA3 rs738409 is associated with a faster eGFR decline during a 5-year follow-up, independent of annual changes in common renal risk factors and use of certain glucose-lowering medications.     

Positive association between body fat percentage and hyperuricemia in patients with hypertension: The China H-type hypertension registry study

Background and aimsThe relationship between the body fat percentage (BFP) and hyperuricemia is still unknown in different gender subjects. The purpose of this study was to determine the magnitude of the association between the BFP and the presence of hyperuricemia in the sex-specific group among hypertensive patients.Methods and resultsWe conducted a cross-sectional study enrolling 14,234 hypertensive participates from the Chinese Hypertension Registry Study. Body fat percentage (BFP) was calculated by simple anthropometric parameters. Hyperuricemia was defined as serum uric acid (SUA) level 420 umol/L in men and 360 umol/L in women. The mean BFP was 24.5% in men and 37.1% in women. Multiple logistic analyses showed that the relationship between BFP with the risk of hyperuricemia in a dose-dependent manner among both men (odds ratio [OR] 1.07, 95% CI 1.06, 1.09) and women (OR 1.08, 95% CI 1.06, 1.09) in the fully adjusted model. Subgroup analyses showed the positive association between BFP and the risk of hyperuricemia was consistent in all stratification subgroups (all P for interaction >0.05).ConclusionFor patients with hypertension, BFP was positively associated with an increased risk of hyperuricemia among both men and women.     

The role of insulin resistance in the relation of visceral,abdominal subcutaneous and total body fat to cardiovascular function

Background and aimsThe separate cardiovascular effects of type 2 diabetes and adiposity remain to be examined. This study aimed to investigate the role of insulin resistance in the relations of visceral (VAT), abdominal subcutaneous (aSAT) adipose tissue and total body fat (TBF) to cardiovascular remodeling.Methods and resultsIn this cross-sectional analysis of the population-based Netherlands Epidemiology of Obesity study, 914 middle-aged individuals (46% men) were included. Participants underwent magnetic resonance imaging. Standardized linear regression coefficients (95%CI) were calculated, adjusted for potential confounding factors. All fat depots and insulin resistance (HOMA-IR), separate from VAT and TBF, were associated with lower mitral early and late peak filling rate ratios (E/A): −0.04 (−0.09;0.01) per SD (54 cm²) VAT; −0.05 (−0.10;0.00) per SD (94 cm²) aSAT; −0.09 (−0.16;-0.02) per SD (8%) TBF; −0.11 (−0.17;-0.05) per 10-fold increase in HOMA-IR, whereas VAT and TBF were differently associated with left ventricular (LV) end-diastolic volume: −8.9 (−11.7;-6.1) mL per SD VAT; +5.4 (1.1;9.7) mL per SD TBF. After adding HOMA-IR to the model to evaluate the mediating role of insulin resistance, change in E/A was −0.02 (−0.07;0.04) per SD VAT; −0.03 (−0.08;0.02) per SD aSAT; −0.06 (−0.13;0.01) per SD TBF, and change in LV end-diastolic volume was −7.0 (−9.7;-4.3) mL per SD VAT. In women, adiposity but not HOMA-IR was related to higher aortic arch pulse wave velocity.ConclusionInsulin resistance was associated with reduced diastolic function, separately from VAT and TBF, and partly mediated the associations between adiposity depots and lower diastolic function.     

Association between serum uric acid levels and cardiovascular risk factors among adults in India

Background and aimThe objective of this study was to explore the association between serum uric acid (SUA) levels and cardiovascular risk factors in the Indian population.Methods and resultsThis was a cross-sectional, population-based study. The study enrolled adults aged 20 years and above residing in rural, sub-urban, and urban. All participants completed a detailed questionnaire, underwent anthropometric measurements, and had blood samples collected. Participants were divided into three tertiles based on their SUA concentrations. A total of 2976 participants were included in this study, with 865 from rural, 1030 from sub-urban, and 1081 from urban populations. The mean values of cardiovascular risk factors were significantly higher in tertile 3 (p < 0.001) as compared to the other tertiles. However, we observed a negative trend between the increase of SUA and SUA/Scr ratio and HbA1c levels (Pearson correlation r = −0.068; p < 0.001 and r = −0.140; p < 0.001, respectively). The healthy and prediabetic groups did not show any significant change in HbA1c with increasing SUA levels, while an inverse trend was observed in diabetics. In the diabetic population, both men and women showed an inverse trend between increasing SUA levels and HbA1c in both known and newly diagnosed diabetes (p < 0.001).ConclusionsThe study found a positive association between SUA levels and cardiovascular risk factors. However, HbA1c was inversely correlated with increasing SUA tertiles in both known and newly diagnosed diabetes, as compared to the general population. Additionally, both men and women with diabetes consistently showed an inverse relationship between increasing SUA/SCr ratio and HbA1c levels.     

Diet quality in association to lipidaemic profile in adults of families at high-risk for type 2 diabetes in Europe: The Feel4Diabetes study

Background and aimsThe role of diet in blood lipids is scarcely investigated in adults at risk of Type 2 Diabetes Mellitus (T2DM) and even less studied regarding their socioeconomic status (SES). This study aimed to investigate the associations of diet quality with blood lipids in adults from families at high-risk for developing T2DM from six European countries, considering their SES.Methods and resultsIn total 2049 adults (67% women) from relatively low-SES regions and high T2DM risk families were enrolled. Dietary habits, sedentary behaviour and sociodemographic characteristics were assessed using standardised questionnaires. The associations of tertiles of healthy diet score (HDS) with blood lipids were tested by univariate analysis of variance (UNIANOVA). HDL-Cholesterol (HDL-C) was positively (B 1.54 95%CI 0.08 to 2.99) and LDL-Cholesterol (LDL-C) (B ?4.15 95%CI ?7.82 to ?0.48), ratio of total cholesterol to HDL-C (B ?0.24 95%CI ?0.37 to ?0.10), ratio of LDL-C to HDL-C (B ?0.18 95%CI ?0.28 to ?0.08) and Atherogenic Index of Plasma (B ?0.03 95%CI ?0.06 to 0.00) inversely associated with the highest tertile of diet score compared to the lowest tertile independently of age, sex, Body Mass Index, total screen time and smoking. In sub-analysis of education (<14 and ≥ 14 years of education), these findings were only significant in the high-SES group.ConclusionWhile diet quality was poorer in the low-SES group, an association between diet quality and lipidemic profile was not found, as increased central obesity and smoking prevalence might have confounded this association. These findings indicate the need for tailor-made interventions, guided by the specific risk factors identified per population sub groups.     

Causal relationship between serum uric acid and abnormal blood pressure based on the panel model study: A 5-year cohort study

Background and aimsTo investigate the relationship between elevated serum uric acid (SUA) levels and blood pressure (BP).Methods and resultsBased on the Beijing Health Management Cohort, 5276 health examination people were enrolled. Cross-lagged model was used to explore the relationship between SUA levels and blood pressure. The results showed: (1) increased SUA and increased systolic blood pressure (SBP): ① The path coefficients from baseline SUA to follow-up SBP were statistically significant in both the general population (β = 0.034, P < 0.05) and men (β = 0.048, P < 0.05). The path coefficients from baseline SBP to follow-up SUA were not statistically significant in either the general population (β = 0.010, P > 0.05) or men (β = 0.011, P > 0.05). ② The path coefficients from baseline SUA to follow-up SBP and from baseline SBP to follow-up SUA were not statistically significant in women with BMI ≥ 25 kg/m² and BMI < 25 kg/m². (2) Increased SUA and diastolic blood pressure (DBP): ① There was no statistical significance between the path coefficients from baseline DBP to follow-up SUA and the path coefficients from baseline SUA to follow-up DBP. ② In men and women, BMI ≥ 25 kg/m² and BMI < 25 kg/m², the path coefficients from baseline DBP to follow-up SUA and from baseline SUA to follow-up DBP were not statistically significant.ConclusionsSUA can increase blood pressure in the general male population; no reverse time sequence relationship was found. The temporal relationships between SUA levels and SBP abnormalities were different in the sex and BMI subgroups. No bidirectional causal temporal relationship was found between SUA elevation and DBP abnormality.     

Sugar- and artificially-sweetened soda consumption and subclinical atherosclerosis among Mexican women

Background and aimsSugar-sweetened soda consumption is associated with most cardiometabolic risk factors. The role of artificially-sweetened beverages in cardiovascular disease (CVD) is inconclusive, but their consumption correlates with health impairment. Little is known about the contribution of soda consumption in subclinical stages of atherosclerosis. Therefore, we evaluated the relation between sugar- and artificially-sweetened soda consumption and carotid intima-media thickness (IMT) among Mexican women.Methods and resultsWe cross-sectionally evaluated 1093 women enrolled in the Mexican Teachers’ Cohort who were free of CVD, diabetes or cancer. Sugar- and artificially-sweetened soda consumption was estimated from a validated 140-item food frequency questionnaire in 2008 and all women underwent a carotid ultrasound assessment three years later. Participants were categorized into tertiles of soda consumption in servings/week. Subclinical atherosclerosis was defined as a mean left and/or right IMT ≥0.8 mm or the presence of plaque on either common carotid artery. In multivariable regression models, women in the highest tertile of sugar-sweetened soda consumption had 2.6% (95%CI: 0.8, 4.5) mean increased IMT, and had 2-fold the risk of carotid atherosclerosis (PR: 2.0, 95%CI: 1.3, 3.2) compared to those in the lowest tertile. In stratified analyses, older and postmenopausal women who consumed sugar-sweetened soda had an increased IMT and atherosclerosis risk. Artificially-sweetened soda consumption was not associated with IMT or carotid atherosclerosis.ConclusionsSugar-sweetened soda consumption was associated with subclinical atherosclerosis among disease-free Mexican women. Public health strategies to decrease CVD should consider the impact of sugar-sweetened soda consumption, particularly in older women.     

Association between body mass index,waist circumference,and relative fat mass with the risk of first unprovoked venous thromboembolism

Background and aimsObesity defined by body mass index (BMI) is independently associated with venous thromboembolism (VTE). Abdominal obesity, defined by waist circumference, is a predictor of cardiovascular events. Recently, relative fat mass (RFM) was proposed as a marker of cardiovascular risk. We assessed the role of three different measures of obesity to predict unprovoked VTE in a longitudinal study.Methods and resultsMoli-sani is a prospective cohort study carried out in the general population of the Molise region, Italy. A total of 23,538 individuals (48% men, age 55.4 years) enrolled between 2005 and 2010 were eligible. Patients on anticoagulant treatment were excluded. BMI ≥30 kg/m² defined obesity, waist circumference >102 cm for men or 88 cm for women defined abdominal obesity, tertiles of RFM were compared. The long-term incidence of first unprovoked VTE during follow-up was assessed. Overall, 29.6% individuals were obese and 44.2% had abdominal obesity. A total of 66 first unprovoked VTE events were diagnosed during a median follow-up of 8.2 years. After multivariable Cox regression analysis, the risk of unprovoked VTE was significantly higher in obese participants (HR 1.89, 95% CI 1.16–3.07) than in participants with BMI <30; in subjects with abdominal obesity than with normal waist circumference (HR 2.19, 1.26–3.81); and in subjects with third vs first RFM tertile index (HR 2.46, 1.15–5.28). The areas under the curves for the models including the three obesity indexes were comparable.ConclusionsThree indexes of obesity based on BMI, waist circumference or RFM similarly predict first occurrence of unprovoked VTE.     

Associations between major dietary patterns and blood pressure among Southwest Chinese: A cross-sectional analysis based on the China Multi-Ethnic Cohort (CMEC) study

Background and aimsIn the less developed multi-ethnic regions (LEMRs) of Southwest China, the associations between dietary patterns and blood pressure (BP) values remain unclear. We aimed to investigate such associations and related effect modifiers.Methods and resultsThis study included 81,433 participants from the China Multi-Ethnic Cohort Study. Dietary intakes during the year before the interview were measured with the Quantitative Food Frequency Questionnaire. Three major dietary patterns that were highly in line with geographical and ethnic distributions of the study population, i.e., “Sichuan Basin,” “Yunnan-Guizhou Plateau,” and “Qinghai-Tibet Plateau,” were derived using principal component factor analysis. The multilinear regression model combined with inverse probability of exposure weighting was used to estimate the associations between dietary patterns and BP values.Comparing the highest with the lowest quintiles, the Sichuan Basin dietary pattern (characterized by urban lifestyles) was associated with 2.67 mmHg lower systolic blood pressure (SBP) (95% CI: −3.07 to −2.27) and 0.89 mmHg lower diastolic blood pressure (95% CI: −1.12 to −0.65). In contrast, both the Yunnan-Guizhou Plateau (characterized by agricultural lifestyles) and the Qinghai-Tibet Plateau dietary patterns (characterized by nomadic lifestyles) showed positive associations with BP. In the stratified analysis, the associations between dietary patterns and SBP were significantly stronger in women than in men for all three kinds of dietary patterns.ConclusionBoth major dietary patterns and their associations with BP showed a substantial disparity in LEMRs of Southwest China. Dietary patterns in regions of higher socioeconomic status are more conducive to reducing the rising of BP, especially for women and urban residents, which might provide insights into the BP control in LEMRs of Southwest China.     

Proposed Stages of Myocardial Phenotype Development in Fabry Disease

ObjectivesThis study sought to explore the Fabry myocardium in relation to storage, age, sex, structure, function, electrocardiogram changes, blood biomarkers, and inflammation/fibrosis.BackgroundFabry disease (FD) is a rare, x-linked lysosomal storage disorder. Mortality is mainly cardiovascular with men exhibiting cardiac symptoms earlier than women. By cardiovascular magnetic resonance, native T1 is low in FD because of sphingolipid accumulation.MethodsA prospective, observational study of 182 FD (167 adults, 15 children; mean age 42 ± 17 years, 37% male) who underwent cardiovascular magnetic resonance including native T1, late gadolinium enhancement (LGE), and extracellular volume fraction, 12-lead electrocardiogram, and blood biomarkers (troponin and N-terminal pro-brain natriuretic peptide).ResultsIn children, T1 was never below the normal range, but was lower with age (9 ms/year, r = −0.78 children; r = −0.41 whole cohort; both p < 0.001). Over the whole cohort, the T1 reduction with age was greater and more marked in men (men: −1.9 ms/year, r = −0.51, p < 0.001; women: −1.4 ms/year, r = −0.47 women, p < 0.001). Left ventricular hypertrophy (LVH), LGE, and electrocardiogram abnormalities occur earlier in men. Once LVH occurs, T1 demonstrates major sex dimorphism: with increasing LVH in women, T1 and LVH become uncorrelated (r = −0.239, p = 0.196) but in men, the correlation reverses and T1 increases (toward normal) with LVH (r = 0.631, p < 0.001), a U-shaped relationship of T1 to indexed left ventricular mass in men.ConclusionsThese data suggest that myocyte storage starts in childhood and accumulates faster in men before triggering 2 processes: a sex-independent scar/inflammation regional response (LGE) and, in men, apparent myocyte hypertrophy diluting the T1 lowering of sphingolipid.     

Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project

Background and aimThe URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes.Methods and resultsThe URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up.A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04–1.47) and CV mortality (HR:1.31, 95%CI:1.03–1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders.ConclusionsSUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.     

Rendimiento y validación del Test del Corazón Saludable para la predicción de mortalidad cardiovascular en población mediterránea a escala nacional

Introduction and objectivesThe Healthy Heart Score (HHS) is a lifestyle-based equation for predicting cardiovascular disease (CVD) risk and may serve as a tool in primordial prevention. However, its performance outside North American populations is unknown. This study assessed the performance of the HHS for estimating CVD mortality in the adult population of Spain.MethodsWe analyzed data from the ENRICA cohort, comprising 10 228 participants free of chronic disease and representative of the Spanish population aged ≥ 18-years, who were recruited from 2008 to 2010 and were followed up to 2020. The HHS includes body mass index, alcohol, physical activity, smoking, and a 5-component dietary score. The HHS was calculated at baseline using the sex-specific beta coefficients from the original development cohorts. Model discrimination was assessed using the Harrell c-statistic and Gonen-Heller c-statistic for survival data, and calibration was evaluated through calibration plots.ResultsAfter a median follow-up of 11.8 years, 110 CVD deaths were ascertained. The discrimination of the HHS was similar for women (Harrell c, 0.91; 95%CI, 0.87-0.95; Gonen-Heller-c, 0.85; 95%CI, 0.83-0.88) and men (Harrell c, 0.91; 95%CI, 0.88-0.94; Gonen-Heller c: 0.85; 95%CI, 0.83-0.88). After recalibration by the sex-specific baseline survival function, the calibration became optimal for: a) all deciles of predicted CVD risk except the highest decile, where HHS underestimated the risk, and b) all age groups except 70 years and older, where there was an underestimation.ConclusionsIn this Spanish cohort, the HHS showed good discrimination and calibration for predicting CVD death. The performance of HHS in other European populations and its implementation in the clinical setting warrants further investigation.     

The association between early-life famine exposure and adulthood obesity on the risk of dyslipidemia

Background and aimsThe joint effect of famine exposure and adulthood obesity on risk of dyslipidemia remains unclear. Thus, we aim to explore the joint effect of famine exposure and adulthood obesity on the risk of dyslipidemia, and the potential effect of adult general or abdominal obesity on the association between famine exposure and dyslipidemia.Methods and resultsWe conducted a community-based cohort study in 8880 subjects aged 40 years or older. Participants were divided into nonexposed, fetal-exposed, childhood-exposed, adolescent-exposed according to birth date. General obesity and abdominal obesity were defined according to body mass index (BMI: overweight≥24.0 kg/m², obesity≥28.0 kg/m²) and waist-to-hip ratio (WHR, men/women: moderate≥0.90/0.85, high≥0.95/0.90). Dyslipidemia was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Compared with nonexposed participants, fetal-exposed individuals had significantly increased risk of dyslipidemia (OR:1.24, 95%CI: 1.03–1.50) in the whole study. Significant increased risk of dyslipidemia related to famine exposure was observed in women [ORs (95%CIs) were 1.36 (1.05–1.76) and 1.70 (1.22–2.37) for the fetal and childhood-exposed group, respectively] but not in men. Moreover, both general and central obesity had significant multiplicative interactions with famine exposure for the risk of dyslipidemia (P for interaction = 0.0001 and < 0.0001, respectively). Significant additive interaction was found between famine exposure and WHR on risk of dyslipidemia in women, with the relative excess risk due to interaction (RERI) and 95% CI of 0.43 (0.10–0.76).ConclusionCoexistence of early-life undernutrition and adulthood obesity was associated with a higher risk of dyslipidemia in later life.     

Associations Between Cardiovascular Risk,Structural Brain Changes,and Cognitive Decline

BackgroundThe impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear.ObjectivesThis study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences.MethodsWithin the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models.ResultsIn all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (β = −0.019; 95% confidence interval [CI]: −0.035 to −0.003), episodic memory (β = −0.023; 95% CI: −0.041 to −0.004), working memory (β = −0.021; 95% CI: −0.035 to −0.007), and perceptual speed (β = −0.027; 95% CI: −0.042 to −0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β = −0.021; 95% CI: −0.042 to −0.000), gray matter (β = −1.569; 95% CI: −2.757 to −0.382), and total brain (β = −1.588; 95% CI: −2.832 to −0.344), and greater volume of white matter hyperintensities (β = 0.035; 95% CI: 0.001 to 0.069).ConclusionsHigher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.     

Low serum creatinine to cystatin C ratio is independently associated with sarcopenia and high carotid plaque score in patients with type 2 diabetes

Background and aimsLow serum creatinine (Cr) to cystatin C (cysC) ratio has been suggested to be associated with low muscle mass and strength and poor prognosis in various chronic disease. We investigated the associations of CCR with sarcopenia and carotid plaque score (PS) in patients with type 2 diabetes mellitus.Methods and resultsA total of 1577 patients with type 2 diabetes were enrolled. High PS was defined as PS ≥ 3. Sarcopenia was assessed by the measurement of appendicular skeletal muscle mass (ASM) and grip strength (GS). Compared to the highest CCR group, the lowest tertile group was older; had higher C-reactive protein levels, CIMT, and PS, but lower cysC-based estimated glomerular filtration rate (cysC-eGFR), ASM/BMI, and GS. Positive correlations between CCR and ASM/BMI (r = 0.239 in men and 0.303 in women, p < 0.001) and GS (r = 0.282 in men and 0.270 in women, p < 0.001) were observed in both genders. Odds ratios and 95% confidence intervals for high PS after adjusting for age and sex were 1.22 (0.92–1.61, p = 0.18) in the middle and 1.74 (1.31–2.30, p < 0.001) in the lowest tertiles, respectively, with those of the lowest tertile remaining significant after further adjusting for multiple confounders.ConclusionsLow CCR was independently associated with sarcopenia and high PS in patients with type 2 diabetes mellitus, especially after adjusting for ASM/BMI and GS.     

Acetabular dysplasia and the risk of developing hip osteoarthritis at 2,5,8, and 10 years follow-up in a prospective nationwide cohort study (CHECK).

ObjectiveTo assess the relationship between acetabular dysplasia (AD) and the risk of incident and end-stage radiographic hip osteoarthritis (RHOA) over 2,5,8 and 10 years.DesignIndividuals (n = 1002) aged between 45 and 65 from the prospective Cohort Hip and Cohort Knee (CHECK) were studied. Anteroposterior pelvic radiographs were obtained at baseline and 2,5,8, and 10-years follow-up. False profile radiographs were obtained at baseline. AD was defined as a lateral center edge angle, an anterior center edge angle, or both <25° at baseline. The risk of developing RHOA was determined at each follow-up moment. Incident RHOA was defined by Kellgren & Lawrence (KL) grade ≥2 or total hip replacement (THR), end-stage RHOA by a KL grade ≥3 or THR. Associations were expressed in odds ratios (OR) using logistic regression with generalized estimating equations.ResultsAD was associated with the development of incident RHOA at 2 years follow-up (OR 2.46, 95% CI 1.00–6.04), 5 years follow-up (OR 2.28, 95% CI 1.20–4.31), and 8 years follow-up (OR 1.86, 95%CI 1.22–2.83). AD was only associated with end-stage RHOA at 5 years follow-up (OR 3.75, 95% CI 1.02–13.77). No statistically significant associations were observed between AD and RHOA at 10-years follow-up.ConclusionBaseline AD in individuals between 45 and 65 years is associated with an increased risk of developing RHOA within 2- and 5 years. However, this association seems to weaken after 8 years and disappears after 10 years.     

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate

ObjectivesThe aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs).BackgroundThe outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined.MethodsPatients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m²), intermediate eGFR (≥60 and <90 mL/min/1.73 m²), and high eGFR (≥90 mL/min/1.73 m²). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year.ResultsPatients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding.ConclusionsThese results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)