Glomerular hyperfiltration as an independent predictor of all-cause mortality in healthy adults: A nationally representative cohort study.

Background: Cystatin C (Cys-C) is a sensitive biomarker of renal function and an independent predictor of all-cause mortality (ACM) in patients with chronic kidney and cardiovascular disease (CVD). Although higher levels of Cys-C are associated with increased body mass index (BMI), the interplay between serum Cys-C, BMI and ACM in adults with normal renal function is unknown. Methods: Utilizing data from the National Health and Nutrition Examination Survey (1999-2002), analysis was conducted on participants (≥18 years) with normal renal function [glomerular filtration rate (GFR) ≥90 ml/min)]. BMI (kg/m2) was categorized as Normal (BMI:18.5-24.9); Overweight (BMI:25-29.9); Obese (BMI >30), while Cys-C (mg/L) was categorized into weight based quartiles [Q1:<0.72(ref); Q2: ≥0.72-0.80; Q3: ≥0.80-0.89; Q4: ≥0.89]. Mortality information was obtained from the National Death Index using probabilistic matching. Cox proportional hazards models (and associated 95% CI’s) estimated the likelihood of ACM by Cys-C quartiles in each BMI category. Results: The mean(±) age and GFR of 2649 participants (51% females) was 50±20 years and 123±28 mL/min, while the median (IQR) of CRP and Cys-C was 0.19(0.07-0.44) mg/dL and 0.80(0.72-0.89) mg/L, respectively. Approximately, 33% of the cohort was normal, 34% overweight, and 33% were obese. After a mean(SD) follow up of 5.9(1.3) years, 213 deaths (all-cause) were observed. Cys-C levels increased with increasing BMI (p trend <0.05), however, significant difference was only seen in obese when compared with normal weight adults (p<0.05). Within each BMI category, increasing Cys-C was associated with increased risk of ACM (p trend <0.05), however, the hazard ratio were statistically significant only at elevated Cys-C levels (Q4 vs.Q1) in normal and overweight adults (both p values <0.05). Conclusions: Independent of traditional CVD risk factors, elevated Cys-C levels predicts risk of ACM in normal and overweight but not in obese adults who have normal renal function based on GFR.

Background and Aims A reduced glomerular filtration rate (GFR) is a definite risk factor for major adverse cardiovascular event (MACE) in acute myocardial infarction (AMI) patients. While glomerular hyperfiltration (GHF) is associated with early phases of kidney disease, it is unclear whether GHF is associated with higher risk of MACE. Method 9,561 AMI patients with estimated GFR ≥ 60 mL/min/1.73 m2 were enrolled from prospective population-based national cohort. GHF was defined as GFR > 90th percentile after adjustment for age, sex, lean body mass and history of diabetes and hypertension, systolic blood pressure, left ventricular ejection fraction and use of angiotensin converting enzyme inhibitor or receptor blocker. Patients were divided into two groups (normal filtration group vs. GHF group) and occurrence of 3-year MACEs after AMI were investigated. Sensitivity analyses with different adjusted variables for hyperfiltration or with different patient exclusion criteria, and propensity score matching were conducted to determine consistency of our results. Results The GFR in 956 patients with GHF was 113.1±13.1 and it was significantly higher than those in normal filtration patients (87.7±13.1; P<0.001). The incidence rate of MACEs was higher in patients with GHF, and patient with GHF showed significantly higher risk of MACEs even after adjustment for several confounders (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.11-1.63) compared to normal filtration patients. GHF group had significantly higher risk of all-cause mortality (HR 1.65; 95% CI 1.26-2.17) and cardiac death (HR 1.80; 95% CI 1.28-2.54). There was no significant difference in the risk of non-cardiac death between two groups. Sensitivity analyses and propensity score matched analysis also showed similar findings. Conclusion GHF was independently associated with increased risk of MACE after AMI and the hazardous effects of GHF was pronounced in all-cause mortality and cardiac death. Our findings suggest that GHF might be a useful marker for predicting MACE after AMI.

BackgroundElevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The purpose of the study was to investigate if SUA was an independent predictor of 5-year all-cause mortality in a propensity score matched cohort of chronic heart failure (HF) outpatients. Furthermore, to assess whether gender or renal function modified the effect of SUA.MethodsPatients (n = 4684) from the Norwegian Heart Failure Registry with baseline SUA were included in the study. Individuals in the highest gender-specific SUA quartile were propensity score matched 1:1 with patients in the lowest three SUA quartiles. The propensity score matching procedure created 928 pairs of patients (73.4% males, mean age 71.4 ± 11.5 years) with comparable baseline characteristics. Kaplan Meier and Cox regression analyses were used to investigate the independent effect of SUA on all-cause mortality.ResultsSUA in the highest quartile was an independent predictor of all-cause mortality in HF outpatients (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.03–1.37, p-value 0.021). Gender was found to interact the relationship between SUA and all-cause mortality (p-value for interaction 0.007). High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% CI 1.24–2.20, p-value 0.001), but not in men (HR 1.06, 95% CI 0.89–1.25, p-value 0.527). Renal function did not influence the relationship between SUA and all-cause mortality (p-value for interaction 0.539).ConclusionsHigh SUA was independently associated with inferior 5-year survival in Norwegian HF outpatients. The finding was modified by gender and high SUA was only an independent predictor of 5-year all-cause mortality in women, not in men.

Associations between plasma homocysteine (Hcy), vitamin B12, and folate and the risk of all-cause mortality are unclear. This study aimed to examine whether plasma Hcy, vitamin B12, and folate levels independently predict the risk of all-cause mortality in American adults with stroke. Data from the United States National Health and Examination Survey (NHANES; 1999-2006) were used and linked with the latest (2019) National Death Index (NDI). Cox proportional hazards models and restricted cubic splines were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality for Hcy, folate, and B12 levels in adults with stroke. Sample weights were calculated to ensure the generalizability of the results. A total of 431 participants were included (average age: 64.8 years). During a median follow-up of 10.4 years, 316 deaths occurred. Hcy was positively associated with all-cause mortality in adults with stroke (HR, 1.053; 95% CI: 1.026-1.080). Stroke patients with plasma Hcy levels in the fourth quartile had a 1.631-fold higher risk of all-cause mortality (HR, 1.631; 95% CI: 1.160-2.291) than those in the first quartile. The association between plasma Hcy and all-cause mortality was strong significant in older patients (p for interaction = 0.020). Plasma folate and vitamin B12 concentrations were inversely correlated with Hcy concentrations [B-value (95% CI): -0.032 (-0.056- -0.008), -0.004 (-0.007- -0.002), respectively]. No significant associations were observed between folate, vitamin B12 levels, and all-cause mortality in adults with stroke. Plasma Hcy levels were positively associated with all-cause mortality in older adults with stroke. Folate and vitamin B12 levels were inversely correlated with Hcy. Plasma Hcy may serve as a useful predictor in mortality risk assessment and targeted intervention in adults with stroke.

Vitamin D deficiency and sleep disorders may independently contribute to increased mortality, but the combined effects of these two factors on mortality remain unknown. This study aimed to investigate both the separate and joint effects of vitamin D deficiency and sleep disorders on cardiovascular disease mortality, as well as all-cause mortality and cancer mortality. We analyzed data from 24,566 adults in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Sleep disorders were assessed using self-report questionnaires, and vitamin D levels were measured through serum total 25-hydroxyvitamin D [25(OH)D]. Cox proportional hazards models were employed to evaluate the associations between separate and joint effects of vitamin D deficiency and sleep disorders with mortality outcomes. Over a median follow-up of 9.08 years, we included a total of 24,566 individuals, in this study. Among them, 2,776 cases were all-cause deaths, 858 were cardiovascular disease deaths, and 644 were cancer deaths. We found that Vitamin D deficiency was independently associated with an increased risk of all-cause mortality, while sleep disorders were similarly associated with a higher risk of all-cause mortality. Notably, participants with both vitamin D deficiency and sleep disorders exhibited a significantly higher risk of all-cause mortality (HR, 2.31; 95% CI: 1.36-3.91) and cardiovascular mortality (HR, 2.39; 95% CI, 1.03-5.58) compared to those with only one or neither risk factor, even after adjusting for potential confounders. Our study highlights that the combination of vitamin D deficiency and sleep disorders was associated with an increased risk of all-cause and cardiovascular mortality in adults. These findings might help to refine dietary and lifestyle intervention strategies for this population.

The trajectory of glomerular filtration rate (GFR) in relation to glomerular hyperfiltration (GHF) has been unknown. It was evaluated retrospectively in 23,982 GHF-free health examinees who were followed for 2-10 yr (mean: 5.1 yr). GFR was estimated by the serum creatinine concentration, and GHF was defined as age- and sex-specific estimated GFR (eGFR) ≥ 95% of the Japanese general population. The temporal profile of eGFR was plotted in a GHF-centered way, which was fitted to a random coefficient linear mixed model. Of the 23,982 subjects, 797 and 23,185 subjects developed or did not develop GHF, respectively, so that they were termed as the GHF(+) and GHF(-) groups. At baseline, median eGFR was significantly elevated in the GHF(+) group compared with in the GHF(-) group: 94.1 versus 77.3 mL/min/1.73 m2 (P < 0.001). Elevation of basal eGFR lasted for a mean (SD) of 3.3 (1.9) yr in the GHF(+) group; mean eGFR then rose to the GHF range, which was 108.5 mL/min/1.73 m2. The eGFR decline after the peak was steeper in the GHF(+) group than in the GHF(-) group: -0.984 versus -0.497 mL/min/1.73 m2/yr (P < 0.001). Baseline eGFR, but no other variable, well predicted incident GHF, with an area under the receiver operating characteristic curve of 0.87 (95% confidence interval: 0.86-0.88). In conclusion, GHF occurs as a chronic, multiphasic phenomenon: initially with a sustained GFR elevation for years, followed by a GFR surge to the GHF range, which was accompanied by accelerated GFR declining.

OBJECTIVEHemoglobin A1c (HbA1c) level has been associated with increased mortality in middle-aged populations. The optimal intensity of glucose control in older adults with diabetes remains uncertain. We sought to estimate the risk of mortality by HbA1c levels among older adults with and without diabetes.RESEARCH DESIGN AND METHODSWe analyzed data from adults aged ≥65 years (n = 7,333) from the Third National Health and Nutrition Examination Survey (NHANES III) (1998–1994) and Continuous NHANES (1999–2004) and their linked mortality data (through December 2011). Cox proportional hazards models were used to examine the relationship of HbA1c with the risk of all-cause and cause-specific (cardiovascular disease [CVD], cancer, and non-CVD/noncancer) mortality, separately for adults with diabetes and without diabetes.RESULTSOver a median follow-up of 8.9 years, 4,729 participants died (1,262 from CVD, 850 from cancer, and 2,617 from non-CVD/noncancer causes). Compared with those with diagnosed diabetes and an HbA1c <6.5%, the hazard ratio (HR) for all-cause mortality was significantly greater for adults with diabetes with an HbA1c >8.0%. HRs were 1.6 (95% CI 1.02, 2.6) and 1.8 (95% CI 1.3, 2.6) for HbA1c 8.0–8.9% and ≥9.0%, respectively (P for trend <0.001). Participants with undiagnosed diabetes and HbA1c >6.5% had a 1.3 (95% CI 1.03, 1.8) times greater risk of all-cause mortality compared with participants without diabetes and HbA1c 5.0–5.6%.CONCLUSIONSAn HbA1c >8.0% was associated with increased risk of all-cause and cause-specific mortality in older adults with diabetes. Our results support the idea that better glycemic control is important for reducing mortality; however, in light of the conflicting evidence base, there is also a need for individualized glycemic targets for older adults with diabetes depending on their demographics, duration of diabetes, and existing comorbidities.

Glomerular hyperfiltration is associated with increased risk of cardiovascular disease in high-risk conditions, but its significance in low-risk individuals is uncertain. To determine whether glomerular hyperfiltration is associated with increased cardiovascular risk in healthy individuals. This was a prospective population-based cohort study, for which enrollment took place from August 2009 to October 2010, with follow-up available through March 31, 2016. Analysis of the data took place in October 2019. The cohort was composed of 9515 healthy individuals, defined as individuals without hypertension, diabetes, cardiovascular disease, estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, or statin and/or aspirin use, identified among 20 004 patients aged 40 to 69 years with health information accessed through the CARTaGENE research platform. Individuals with glomerular hyperfiltration (eGFR >95th percentile after stratification for sex and age) were compared with individuals with normal filtration rate (eGFR 25th-75th percentiles). Adverse cardiovascular events were defined as a composite of cardiovascular mortality, myocardial infarction, unstable angina, heart failure, stroke, and transient ischemic attack. Risk of adverse cardiovascular events was assessed using Cox and fractional polynomial regressions and propensity score matching. From the 20 004 CARTaGENE participants, 9515 healthy participants (4050 [42.6%] male; median [interquartile range] age, 50.4 [45.9-55.6] years) were identified. Among these, 473 had glomerular hyperfiltration (median [interquartile range] eGFR, 112 [107-115] mL/min/1.73 m2) and 4761 had a normal filtration rate (median [interquartile range] eGFR, 92 [87-97] mL/min/1.73 m2). Compared with the normal filtration rate, glomerular hyperfiltration was associated with an increased cardiovascular risk (hazard ratio, 1.88; 95% CI, 1.30-2.74; P = .001). Findings were similar with propensity score matching. The fractional polynomial regression showed that only the highest eGFR percentiles were associated with increased cardiovascular risk. The cardiovascular risk of individuals with glomerular hyperfiltration was similar to that of the 597 participants with an eGFR between 45 and 60 mL/min/1.73 m2 (hazard ratio, 0.90; 95% CI, 0.56-1.42; P = .64). These findings suggest that glomerular hyperfiltration is independently associated with increased cardiovascular risk in middle-aged healthy individuals. This risk profile appears to be similar to stage 3a chronic kidney disease.

BackgroundObesity is a complex chronic disease associated with several adverse health outcomes that increase mortality risk. Physical activity (PA) is recommended for the prevention and treatment of obesity and is related to a decreased risk of cardiovascular disease, cancer and all-cause mortality. This systematic review and meta-analysis estimates the effect of PA levels on mortality (cardiovascular, cancer and all-cause mortality) in adults with obesity.MethodsA systematic search was conducted in MEDLINE, Embase, Web of Science and SPORTDiscus from inception to June 2024. Prospective cohort studies that explored the association between PA and mortality in adults with obesity (according to their body mass index, ≥ 30 kg/m2) aged ≥ 18 years were included. Our main outcomes were all-cause mortality, and cardiovascular, and cancer mortality reported in primary studies by hazard ratios or relative risk, which were pooled for the meta-analysis when at least two studies reported the effect estimate for the same outcome. The PRISMA recommendations and the MOOSE guidelines were followed. The reported mortality risk estimates comparing insufficiently active versus active (moderate to very active) adults with obesity were pooled using the DerSimonian and Laird random-effects model.ResultsA total of 9 prospective cohort studies involving 199,425 adults with obesity (age range: 35–85 years) were included, of which 59,873 were insufficiently active and 84,328 were active. Active individuals had a 21% lower risk of all-cause mortality (HR: 0.79, 95%CI: 0.74 to 0.84; I2 = 38.2%), and a 24% lower risk of cardiovascular mortality (HR: 0.76, 95%CI: 0.66 to 0.87; I2 = 0.0%) than insufficiently active individuals. The HR for cancer mortality was 0.91 (95%CI: 0.80 to 1.02; I2 = 0.0%), and although this was mostly consistent with a benefit, it was based on only two studies.ConclusionOur data support that moderate to high levels of PA are associated with a 21% lower risk of all-cause and 24% cardiovascular disease mortality in adults with obesity. Although data from the only two published studies seem to indicate a protective effect of PA on cancer risk, the estimates are not statistically significant.Systematic review registrationPROSPERO CRD42022309346.

Introduction and aimsThe world is rapidly ageing. Tooth loss, the consequence of various age-related oral diseases, leads to decreased chewing function and has emerged as a significant public health concern. The aim of this study was to investigate the association between masticatory function and mortality in older adults.MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2009-2018 were analysed. Mortality details were obtained from the National Death Index (NDI). Chewing capacity was determined by the number of functional tooth units (FTUs) that was defined as pairs of opposing natural and artificial teeth in the premolar and molar regions. Weighted Cox proportional hazards models were employed to assess the relationship between FTU and mortality risk. Propensity score matching (PSM) analyses and subgroup analyses were conducted to further assess the association between FTU and mortality.Results5,780 individuals aged 60 and above were involved in this study. The risk of all-cause mortality (HR = 2.4, 95%CI 1.8-3.3) was higher for participants with 0 ≤ FTUs ≤ 3 compared to those in the 10 ≤ FTUs ≤ 12 group. After PSM, a significant increase in the risk of all-cause mortality (HR = 1.8, 95%CI 1.4-2.2) was observed in the 0 ≤ FTUs ≤ 3 group compared to the reference group. Subgroup analyses revealed consistent results across all subgroups.ConclusionsThe findings revealed an association between impaired masticatory function and an increased risk of all-cause mortality among older adults.Clinical RelevanceStudy findings show that maintaining and enhancing oral function may help to promote healthy longevity. They also offer guidance for decision-making among older adults and their caregivers.

Associations of vitamin B6 turnover rate with the risk of cardiovascular and all-cause mortality in hypertensive adults

Combined effect of falling difficulty and cardiovascular diseases on the risk of all-cause and cardiovascular mortality in older adults: an analysis of the National Health and Nutrition Examination Survey.

Visceral obesity is an important risk factor for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). The body roundness index (BRI) is a novel indicator that demonstrates a stronger correlation with visceral fat than other anthropometric indices. However, the association between the BRI and mortality risk in patients with MASLD remains unclear. Therefore, this study investigated the relationship between the BRI and the risks of all-cause and cardiovascular disease mortality among patients with MASLD. This study included 7,428 adults aged ≥18 years with MASLD, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database spanning from 1999 to 2018. The assessment of MASLD was conducted based on the fatty liver index (FLI). To examine the relationship between the BRI and mortality risks, multivariable Cox proportional hazards regression models, trend analysis, and restricted cubic spline curves were employed. Additionally, subgroup analyses were conducted to assess whether the association between the BRI and mortality varied across different subgroups. In total, 1,249 participant deaths were recorded during a median follow-up period of 115 months, of which 404 were attributed to cardiovascular disease. After adjusting for multiple covariates in the fully adjusted model, the risk of all-cause mortality was increased by 27% (HR: 1.27; 95% CI: 1.00-1.60) and 52% (HR: 1.52; 95% CI: 1.18-1.96) in BRI quartiles 3 to 4 (Q3-Q4) compared with Q1, respectively. Similarly, the risk of cardiovascular disease mortality was increased by 61% (HR, 1.61; 95% CI, 1.05-2.46), 62% (HR, 1.62; 95% CI, 1.03-2.53), and 144% (HR, 2.44; 95% CI, 1.46-4.09) in BRI quartiles 2 to 4 (Q2-Q4) compared with Q1, respectively. The restricted cubic spline curves indicated a linear relationship between the BRI and both all-cause and cardiovascular disease mortality (p for non-linearity >0.05). In this nationally representative sample of adults with MASLD from the non-institutionalized civilian population in the United States, the BRI served as an independent predictor of both all-cause and cardiovascular disease mortality. Specifically, higher BRI values were associated with increased risks of both all-cause and cardiovascular disease mortality among patients with MASLD.

Our study aims to evaluate the associations between the serum cobalamin (vitamin B12) and related biomarkers with mortality in hypertensive adults. Data on serum cobalamin from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2014 were included. Mortality status was linked to National Death Index mortality data through 31 December, 2019. Cox regression and restricted cubic spline (RCS) analyses were used to determine the hazard ratios (HRs) and 95% CIs for mortality risk. A total of 9934 hypertensive adults were included in the analysis (mean age, 58.1 ± 17.5 years; 4899 [49.3%] men). At 11.0 years of mean follow-up, 935 cardiovascular deaths and 3096 all-cause deaths were identified. Compared to the third quartiles, the first and fourth quartiles of serum cobalamin were associated with risk of cardiovascular mortality, with multivariable-adjusted HRs of 1.26 (1.05-1.53) and 1.40 (1.17-1.68). Similar results were observed in the relationship between serum cobalamin and all-cause mortality. These results were supported by the RCS analysis. The inflection points for the nonlinear associations of serum cobalamin with cardiovascular and all-cause mortality were 649.9 pg/mL and 577.2 pg/mL, respectively. In addition, compared with the second quartile of circulating methylmalonic acid (MMA, a cobalamin-deficiency marker), this association with the fourth quartile was evident for an increased rate of cardiovascular and all-cause mortality, with 111% (HR = 2.11, 1.71-2.61) and 73% (HR = 1.73, 1.55-1.93) increase. Findings suggest that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults. This study was a prospective cohort study that included serum cobalamin data from 9934 hypertensive adults from the NHANES from 1999-2006 and 20011-2014. Findings suggested that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide and tirzepatide, provide cardiometabolic benefits to patients with type 2 diabetes and obesity, but their potential benefits in mitigating neurodegenerative and cerebrovascular diseases remain unclear. To evaluate the association of semaglutide and tirzepatide with the incidence of dementia, Parkinson disease, ischemic stroke, intracerebral hemorrhage, and all-cause mortality compared with other antidiabetic drugs in adults with type 2 diabetes and obesity. This retrospective cohort study analyzed electronic health record-based data from the TriNetX US network (December 1, 2017, to June 30, 2024) in adults aged 40 years or older with type 2 diabetes and obesity initiating semaglutide, tirzepatide, or other antidiabetic drugs, excluding those with prior neurodegenerative or cerebrovascular diseases. Propensity score matching was used to balance the baseline characteristics. Patients treated with antidiabetic drugs were categorized as GLP-1RA (semaglutide or tirzepatide) or other antidiabetic drug (biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, thiazolidinediones, and α-glucosidase inhibitors) users. The primary outcomes were the incidence of neurodegenerative diseases (dementia, Parkinson disease, and mild cognitive impairment) and cerebrovascular (stroke and intracerebral hemorrhage) diseases, while the secondary outcome was all-cause mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs. A total of 60 860 adults with type 2 diabetes and obesity were included, with 30 430 each in the GLP-1RA group (mean [SD] age, 57.9 [9.9] years; 50.2% female) and the other antidiabetic drug group (mean [SD] age, 58.0 [10.8] years; 51.4% female) after propensity score matching. During a 7-year follow-up, GLP-1RA users had a lower risk of dementia (HR, 0.63; 95% CI, 0.50-0.81), stroke (HR, 0.81; 95% CI, 0.70-0.93), and all-cause mortality (HR, 0.70; 95% CI, 0.63-0.78), with no significant differences in the risk of Parkinson disease or intracerebral hemorrhage. Subgroup analyses revealed greater benefits in patients aged 60 years or older, women, and patients with a body mass index of 30 to 40. In this cohort study, the use of GLP-1RAs semaglutide and tirzepatide was associated with a lower risk of dementia, stroke, and all-cause mortality in adults with type 2 diabetes and obesity. These findings suggest potential neuroprotective and cerebrovascular benefits of GLP-1RAs beyond glycemic control, warranting further trials to confirm these outcomes.