Fasting serum potassium and long-term mortality in healthy men.
Ontology highlight
ABSTRACT: Background
Serum potassium levels have been positively associated with cardiovascular mortality, but little is known about the association with cancer mortality and death due to other causes. We examined whether serum levels of potassium were associated with long-term mortality in a healthy cohort.Methods
Oslo Ischemia Study invited 2341 initially healthy men aged 40-59 years with no use of medication to a comprehensive health survey in 1972. Fasting serum level of potassium (mmol/L) was ascertained at baseline for 1989 men. We have complete follow-up for death throughout 2017. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted for multiple confounders.Results
After a median follow-up of 30 years (interquartile range 21.2-38.7), 1736 deaths were observed, of which 494 were cancer deaths, 688 cardiovascular deaths, and 536 deaths related to other causes. Restricted cubic spline analysis showed that potassium level was linearly and positively associated with long-term cancer mortality; HR per mmol/L 1.8, 95% CI 1.4-2.4. Compared with low levels of potassium (≤ 4.0 mmol/L), men with high levels (≥4.6 mmol/L) showed a significantly 78% higher risk of cancer death. A positive linear association was found for all-cause mortality (HR per mmol/L 1.6, 95% CI 1.4-1.8), and for cardiovascular (HR per mmol/L 1.4, 95% CI 1.1-1.7) and other cause mortality (HR per mmol/L 1.7, 95% CI 1.3-2.2).Conclusions
These findings suggest that serum potassium level appears to predict long-term mortality in healthy middle-aged men, and it might imply future surveillance strategies for individuals with high serum potassium levels.
SUBMITTER: Falk RS
PROVIDER: S-EPMC8045339 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundFasting is attracting an increasing interest as a potential strategy for managing diseases, including metabolic disorders and complementary cancer therapy. Despite concerns of clinicians regarding protein catabolism and muscle loss, evidence-based clinical data in response to long-term fasting in healthy humans are scarce. The objective of this study was to measure clinical constants, metabolic, and muscular response in healthy men during and after a 10 day fast combined with a physical activity programme.MethodsSixteen men (44 ± 14 years; 26.2 ± 0.9 kg/m2 ) fasted with a supplement of 200-250 kcal/day and up to 3 h daily low-intensity physical activity according to the peer-reviewed Buchinger Wilhelmi protocol. Changes in body weight (BW) and composition, basal metabolic rate (BMR), physical activity, muscle strength and function, protein utilization, inflammatory, and metabolic status were assessed during the 10 day fast, the 4 days of food reintroduction, and at 3 month follow-up.ResultsThe 10 day fast decreased BW by 7% (-5.9 ± 0.2 kg, P < 0.001) and BMR by 12% (P < 0.01). Fat mass and lean soft tissues (LST) accounted for about 40% and 60% of weight loss, respectively, -2.3 ± 0.18 kg and -3.53 ± 0.13 kg, P < 0.001. LST loss was explained by the reduction in extracellular water (44%), muscle and liver glycogen and associated water (14%), and metabolic active lean tissue (42%). Plasma 3-methyl-histidine increased until Day 5 of fasting and then decreased, suggesting that protein sparing might follow early proteolysis. Daily steps count increased by 60% (P < 0.001) during the fasting period. Strength was maintained in non-weight-bearing muscles and increased in weight-bearing muscles (+33%, P < 0.001). Glycaemia, insulinemia, blood lipids, and blood pressure dropped during the fast (P < 0.05 for all), while non-esterified fatty acids and urinary beta-hydroxybutyrate increased (P < 0.01 for both). After a transient reduction, inflammatory cytokines returned to baseline at Day 10 of fasting, and LST were still lower than baseline values (-2.3% and -3.2%, respectively; P < 0.05 for both).ConclusionsA 10 day fast appears safe in healthy humans. Protein loss occurs in early fast but decreases as ketogenesis increases. Fasting combined with physical activity does not negatively impact muscle function. Future studies will need to confirm these first findings.
| S-EPMC8718030 | biostudies-literature
Project description:ObjectiveA number of observational studies have shown an inverse association between circulating 25-hydroxyvitamin D and total mortality, but a reverse J-shaped association has also been reported. In a large nested case-control study, serum-25-hydroxyvitamin D (s-25(OH)D) was positively associated with incident prostate cancer. Based on the same study population, the primary aim of the present study was to investigate the association between s-25(OH)D and total mortality.MethodsMen participating in population based health screenings during 1981-1991 and enrolled in a nested case-control study were followed throughout 2007 with respect to all-cause and cause-specific mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression.ResultsIn men with prostate cancer (n = 2282), there was a significant inverse association between s-25(OH)D and total mortality after controlling for potential confounders (HR = 1.25 (95% CI 1.05-1.50), s-25(OH)D <50 nmol/l versus s-25(OH)D ? 50 nmol/l). The corresponding figure among controls (n = 2147) was HR = 1.15 (95% CI 0.88-1.50) and in the total study population HR = 1.19 (95% CI 1.03-1.38). For cause-specific deaths, we found no significant associations.ConclusionsIn this study population, s-25(OH)D was inversely associated with total mortality during more than two decades of follow-up, despite, as previous reported, high s-25(OH)D was associated with increased risk of prostate cancer.
| S-EPMC4795600 | biostudies-literature
Project description:AimsDiuretic treatment is often needed in acute heart failure following myocardial infarction (MI) and carries a risk of abnormal potassium levels. We examined the relation between different levels of potassium and mortality.Methods and resultsFrom Danish national registries we identified 2596 patients treated with loop diuretics after their first MI episode where potassium measurement was available within 3 months. All-cause mortality was examined according to seven predefined potassium levels: hypokalaemia <3.5 mmol/L, low normal potassium 3.5-3.8 mmol/L, normal potassium 3.9-4.2 mmol/L, normal potassium 4.3-4.5 mmol/L, high normal potassium 4.6-5.0 mmol/L, mild hyperkalaemia 5.1-5.5 mmol/L, and severe hyperkalaemia: >5.5 mmol/L. Follow-up was 90 days and using normal potassium 3.9-4.2 mmol/L as a reference, we estimated the risk of death with a multivariable-adjusted Cox proportional hazard model. After 90 days, the mortality rates in the seven potassium intervals were 15.7, 13.6, 7.3, 8.1, 10.6, 15.5, and 38.3%, respectively. Multivariable-adjusted risk for death was statistically significant for patients with hypokalaemia [hazard ratio (HR): 1.91, confidence interval (95%CI): 1.14-3.19], and mild and severe hyperkalaemia (HR: 2, CI: 1.25-3.18 and HR: 5.6, CI: 3.38-9.29, respectively). Low and high normal potassium were also associated with increased mortality (HR: 1.84, CI: 1.23-2.76 and HR: 1.55, CI: 1.09-2.22, respectively).ConclusionPotassium levels outside the interval 3.9-4.5 mmol/L were associated with a substantial risk of death in patients requiring diuretic treatment after an MI.
| S-EPMC4900739 | biostudies-literature
Project description:Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term T alterations were induced. We designed a human model of 30 healthy young males with pharmacologically induced T changes, which resulted in three time points for blood collection: (A) baseline, (B) low T (3 weeks post administration of gonadotropin releasing hormone antagonist) and (C) restored T (2 weeks after injection of T undecanoate). The influence of T on AAs was analyzed by spectrophotometry on plasma samples. Levels of 9 out of 23 AAs, of which 7 were essential AAs, were significantly increased at low T and are restored upon T supplementation. Levels of tyrosine and phenylalanine were most strongly associated to T changes. Short-term effect of T changes suggests an increased protein breakdown that is restored upon T supplementation. Fasting AA levels are able to monitor the early metabolic changes induced by the T fluctuations.
| S-EPMC8619397 | biostudies-literature
Project description:To examine the effect of socioeconomic factors on survival in black and white patients with local or regional prostate cancer.All cases (n = 2046) of clinically localized prostate cancer diagnosed from 1990 to 2000 at the Henry Ford Health System and the Henry Ford Medical Group, equal access health centers, were included. Data on the stage, grade, age at diagnosis, socioeconomic status, treatment given, comorbidities, and vital statistics were gathered from the Henry Ford Medical Group tumor registry and computerized databases, pathologic reports, patient charts, Surveillance, Epidemiology, and End Results database, and the national death registry. The endpoints were the overall and cancer-specific survival. Survival was calculated using Cox proportional hazards regression models.Of the 2046 cases, 1243 were white and 803 were black. Black patients were more likely to have lower incomes, a greater baseline prostate-specific antigen level, and greater comorbidities. They were also more likely to undergo radiotherapy and less likely to undergo radical prostatectomy. Univariate analysis, with white race as the baseline hazard, showed that black patients had significantly increased cancer-specific (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.01-2.13) and overall (HR 1.29, 95% CI 1.09-1.53) mortality. However, adjusting for insurance status and income on multivariate analysis revealed no significant differences in cancer-specific (HR 1.04, 95% CI 0.66-1.64) and overall (HR 0.96, 95% CI 0.78-1.18) survival.In this cohort, socioeconomic factors were sufficient to explain the disparity in survival between white and black patients. Survival differences disappeared after adjusting for income status on multivariate analysis.
| S-EPMC5557082 | biostudies-other
Project description:BackgroundRecent studies suggest that potassium levels may differ by race. The basis for these differences and whether associations between potassium levels and adverse outcomes differ by race are unknown.Study designObservational study.Setting & participantsAssociations between race and potassium level and the interaction of race and potassium level with outcomes were investigated in the Racial and Cardiovascular Risk Anomalies in Chronic Kidney Disease (RCAV) Study, a cohort of US veterans (N=2,662,462). Associations between African ancestry and potassium level were investigated in African Americans in the Atherosclerosis Risk in Communities (ARIC) Study (N=3,450).PredictorsRace (African American vs non-African American and percent African ancestry) for cross-sectional analysis; serum potassium level for longitudinal analysis.OutcomesPotassium level for cross-sectional analysis; mortality and end-stage renal disease for longitudinal analysis.ResultsThe RCAV cohort was 18% African American (N=470,985). Potassium levels on average were 0.162mmol/L lower in African Americans compared with non-African Americans, with differences persisting after adjustment for demographics, comorbid conditions, and potassium-altering medication use. In the ARIC Study, higher African ancestry was related to lower potassium levels (-0.027mmol/L per each 10% African ancestry). In both race groups, higher and lower potassium levels were associated with mortality. Compared to potassium level of 4.2mmol/L, mortality risk associated with lower potassium levels was lower in African Americans versus non-African Americans, whereas mortality risk associated with higher levels was slightly greater. Risk relationships between potassium and end-stage renal disease were weaker, with no difference by race.LimitationsNo data for potassium intake.ConclusionsAfrican Americans had slightly lower serum potassium levels than non-African Americans. Consistent associations between potassium levels and percent African ancestry may suggest a genetic component to these differences. Higher and lower serum potassium levels were associated with mortality in both racial groups.
| S-EPMC5526716 | biostudies-literature
Project description:High serum glucose to potassium ratio (GPR) at admission is implicated for a poor outcome in acute brain injury, acute intracranial hemorrhage, and aneurysmal subarachnoid hemorrhage. However, the relationship between GPR and the outcome of ischemic stroke (IS) remains unknown. In all, 784 IS patients from a large emergency Norwegian cohort were included for secondary analysis. The exposure and outcome were GPR at baseline and all-cause mortality within 30 days after the first admission. Multivariable logistic regression analysis was performed to estimate the risk of 30-day mortality based on GPR levels. In addition, we examined whether there was a nonlinear relationship between admission GPR and 30-day mortality using two-piecewise linear regression with a smoothing function and threshold level analysis. The results of multivariable regression analysis showed that GPR at baseline was positively associated with the 30-day mortality (OR 2.01, 95% CI 1.12, 3.61) after adjusting for potential confounders (age, gender, department, serum sodium, serum albumin, serum-magnesium, hypertension, heart failure, chronic renal failure, and pneumonia). When GPR was translated to a categorical variable, the ORs and 95% CIs in the tertiles 2 to 3 versus the tertile 1 were 1.24 (0.60, 2.56) and 2.15 (1.09, 4.24), respectively (P for trend = 0.0188). Moreover, the results of the two-piecewise linear regression and curve fitting revealed a linear relationship between GPR and 30-day mortality. In IS patients, GPR is positively correlated with 30-day mortality, and the relationship between them is linear. The GPR at admission may be a promising predictor for the short-term outcome in IS patients.
| S-EPMC9114007 | biostudies-literature
Project description:BackgroundIntermittent fasting (IF) is defined as an eating pattern without calorie restrictions, alternating between periods of fasting and eating. In the past decades IF has not only become a popular weight-reducing diet but is thought to improve Quality of Life (QoL) and fatigue. However, very little evidence exists for the general population. Thus, we aimed to assess the impact of a 16-h fasting period per day over a three-month study period on QoL and especially fatigue in healthy people.MethodsWe conducted a prospective cohort study including healthy subjects. All participants fasted 16 h for at least five days a week while maintaining their normal lifestyle. In the study, we analysed blood samples as well as QoL through standardized questionnaires (WHO-5 questionnaire, Short Form Health 36). Furthermore, we measured the degree of fatigue with the Fatigue Assessment Scale (FAS) and Fatigue Severity Scale (FSS) as well as compliance, activity records, and weight alterations. All endpoints were evaluated at baseline, after two weeks, four weeks, and three months of IF.ResultsA total of 30 participants fasted for the entire study period. The results of the WHO-5 questionnaire (15.6 ± 4.6 vs. 18 ± 3.6, p < 0.0019) demonstrated a significant increase in QoL. For long-term QoL six out of eight domains measured by the Short Form Health 36 (SF-36) significantly improved (e.g., physical health: 92.3 ± 11.6 vs. 96.5 ± 6.3, p = 0.015; mental health: 75.5 ± 12.0 vs. 81.7 ± 9.0; p < 0.001 and body pain: 74.1 ± 31.8 vs. 89.5 ± 14.9; p = 0.008) after three months. Fatigue significantly decreased from 10.3 ± 3.2 to 8.4 ± 2.5; p = 0.002 for mental fatigue and from 12.6 ± 3.8 to 10.7 ± 3.3; p = 0.002 measured by the FAS. The mean FSS-Score at baseline was 3.5 ± 1.2 compared to 2.9 ± 1.1 (scale 1-7) after three months (p < 0.001). Notably, the proliferation marker IGF-1 was significantly reduced. No clinically significant changes in laboratory parameters were observed that would have endangered a participant's safety.ConclusionsIF according to the 16:8 regime over a fasting period of three months significantly improved several aspects of the QoL and decreased fatigue in healthy people, while maintaining a good safety profile. The practicability of this diet was also demonstrated for shift workers and people with a high percentage of active labour. Apart from the improvement in QoL and fatigue, the significant reduction in IGF-1, which can act as an accelerator of tumour development and progression, might be an indicator of the potential benefits of IF for patients with cancer.
| S-EPMC9571750 | biostudies-literature
Project description:Treatment with mirtazapine, a widely prescribed antidepressant, has been linked to weight gain and dyslipidemia. Whether dyslipidemia occurs secondary to increased appetite due to antidepressant treatment, or due to direct pharmacological effects of mirtazapine is unknown. The aim of this analysis is to complement our previously published results of the effect of mirtazapine on metabolism and energy substrate partitioning from a proof-of-concept, open-label clinical study (ClinicalTrials.gov NCT00878540) in 12 healthy males (20-25 years). We report the effect of a seven-day administration of mirtazapine 30 mg per day on weight and lipid metabolism in healthy men under highly standardized conditions with respect to diet, physical activity and day-night-rhythm and under continuous clinical observation. After a 7-day administration of mirtazapine 30 mg, we observed a statistically significant increase in triglyceride levels (mean change + 4.4 mg/dl; 95% CI [- 11.4; 2.6]; p = 0.044) as well as TG/HDL-C ratio (mean change + 0.2; 95% CI [- 0.4; 0.1]; p = 0.019) and a decrease in HDL-cholesterol (mean change - 4.3 mg/dl; 95% CI [2.1; 6.5]; p = 0.004), LDL-cholesterol (mean change - 8.7 mg/dl; 95% CI [3.8; 13.5]; p = 0.008), total cholesterol (mean change - 12.3 mg/dl; 95% CI [5.4; 19.1]; p = 0.005), and non-HDL-C (mean change - 8.0 mg/dl; 95% CI [1.9; 14.0]; p = 0.023). Notably, weight (mean change - 0.6 kg; 95% CI [0.4; 0.8]; p = 0.002) and BMI (mean change - 0.2; 95% CI [0.1; 0.2]; p = 0.002) significantly decreased. No change in waist circumference (mean change - 0.4 cm; 95% CI [- 2.1; 2.9]; p = 0.838) or waist-to-hip-ratio (mean change 0.0; 95% CI [- 0.0; 0.0]; p = 0.814) was observed. This is the first study showing unfavorable changes in lipid metabolism under mirtazapine in healthy individuals despite highly standardized conditions including dietary restriction, and despite the observation of a decrease of weight. Our findings support the hypothesis that mirtazapine has direct pharmacological effects on lipid metabolism. ClinicalTrials.gov: NCT00878540.
| S-EPMC10409833 | biostudies-literature
Project description:BackgroundOptogenetic tools allow precise manipulation of neuronal activity via genetically encoded light-sensitive proteins. Currently available optogenetic inhibitors are not suitable for prolonged use due to short-lasting photocurrents, tissue heating, and unintended changes in ion distributions, which may interfere with normal neuron physiology. To overcome these limitations, a novel potassium channel-based optogenetic silencer, named PACK, was recently developed. The PACK tool has two components: a photoactivated adenylyl cyclase from Beggiatoa (bPAC) and a cAMP-dependent potassium channel, SthK, which carries a large, long-lasting potassium current in mammalian cells. Previously, it has been shown that activating the PACK silencer with short light pulses led to a significant reduction of neuronal firing in various in vitro and acute in vivo settings. Here, we examined the viability of performing long-term studies in vivo by looking at the inhibitory action and side effects of PACK and its components in healthy and epileptic adult male mice.ResultsWe targeted hippocampal cornu ammonis (CA1) pyramidal cells using a viral vector and enabled illumination of these neurons via an implanted optic fiber. Local field potential (LFP) recordings from CA1 of freely moving mice revealed significantly reduced neuronal activity during 50-min intermittent (0.1 Hz) illumination, especially in the gamma frequency range. Adversely, PACK expression in healthy mice induced chronic astrogliosis, dispersion of pyramidal cells, and generalized seizures. These side effects were independent of the light application and were also present in mice expressing bPAC without the potassium channel. Light activation of bPAC alone increased neuronal activity, presumably via enhanced cAMP signaling. Furthermore, we applied bPAC and PACK in the contralateral hippocampus of chronically epileptic mice following a unilateral injection of intrahippocampal kainate. Unexpectedly, the expression of bPAC in the contralateral CA1 area was sufficient to prevent the spread of spontaneous epileptiform activity from the seizure focus to the contralateral hippocampus.ConclusionOur study highlights the PACK tool as a potent optogenetic inhibitor in vivo. However, further refinement of its light-sensitive domain is required to avoid unexpected physiological changes.
| S-EPMC8760681 | biostudies-literature