Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

Aims: Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. Methods and results: We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria

Albuminuria as a predictor of cardiovascular outcomes in patients with acute myocardial infarction

Background. In patients with myocardial infarction ( MI ), reduced kidney function is recognized as an important predictor of poor prognosis, but the impact of albuminuria, a representative measure of kidney damage, has not been extensively evaluated. Methods and Results. In the SCREAM (Stockholm Creatinine Measurements) project (2006-2012), we identified 2469 patients with incident MI with dipstick proteinuria measured within a year before MI (427 patients also had urine albumin to creatinine ratio [ ACR ] measured concurrently) and obtained estimates for ACR with multiple imputation in participants with data solely on dipstick proteinuria. We quantified the association of ACR with the post- MI composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI , ischemic stroke, or heart failure using Cox models and then evaluated the improvement in C statistic. During a median follow-up of 1.0 year after MI , 1607 participants (65.1%) developed the post- MI composite outcome. Higher ACR levels were independently associated with all outcomes except for ischemic stroke. Per 8-fold higher ACR (eg, 40 versus 5 mg/g), the hazard ratio of composite outcome was 1.21 (95% CI , 1.08-1.35). The addition of the ACR improved the C statistic of the post- MI composite by 0.040 (95% CI, 0.030-0.051). Largely similar results were obtained regardless of diabetic status and when ACR or dipstick was separately analyzed without imputation. Conclusions. In patients with MI , albuminuria was a potent predictor of subsequent outcomes, suggesting the importance of paying attention to the information on albuminuria, in addition to kidney function, in this high-risk population

Periodontal disease measures and risk of incident peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) Study

BackgroundThe association of periodontal disease with atherosclerotic cardiovascular diseases is well known, but not specifically with incident peripheral artery disease (PAD). Therefore, we studied the associations of periodontal disease with incident PAD in a population-based setting.MethodsAmong 9,793 participants (aged 53-75 years) without prevalent PAD, self-reported history of periodontal disease was ascertained. Of these, 5,872 participants underwent full-mouth examinations from which periodontal status was defined using the US Centers for Disease Control and Prevention-American Academy of Periodontology (CDC-AAP) definition. We quantified the association of periodontal disease with incident PAD (defined by hospital admission diagnosis or procedures) using multivariable Cox regression models.ResultsDuring a median follow-up of 20.1 years, 360 participants (3.6%) developed PAD. In models accounting for potential confounders including diabetes and smoking pack-years, there was higher hazard of PAD in participants with self-reported tooth loss because of periodontal disease (hazard ratio:1.54 [95% CI:1.20-1.98]), history of periodontal disease treatment (1.37 [1.05-1.80]), and periodontal disease diagnosis (1.38 [1.09-1.74]), compared to their respective counterparts. The clinical measure of periodontal disease (n = 5,872) was not significantly associated with incident PAD in the fully adjusted model (e.g., 1.53 [0.94-2.50] in CDC-AAP-defined severe periodontal disease versus no disease).ConclusionWe observed a modest association of self-reported periodontal disease, especially when resulting in tooth loss, with incident PAD in the general population. Nonetheless, a larger study with the clinical measure of periodontal disease is warranted

Total Cholesterol and Cancer Risk in a Large Prospective Study in Korea

Purpose: To further clarify the relationship between total cholesterol and cancer, which remains unclear. Methods: We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death.Results: Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (≥ 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend ≤ .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001).Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32). Conclusion: In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site

Association of Kidney Disease Measures with Cause-Specific Mortality: The Korean Heart Study

<div><p>Background</p><p>The link of low estimated glomerular filtration rate (eGFR) and high proteinuria to cardiovascular disease (CVD) mortality is well known. However, its link to mortality due to other causes is less clear.</p><p>Methods</p><p>We studied 367,932 adults (20–93 years old) in the Korean Heart Study (baseline between 1996–2004 and follow-up until 2011) and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases), cancer (4,035 cases), and other (non-CVD/non-cancer) causes (3,152 cases) after adjusting for potential confounders.</p><p>Results</p><p>Although cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD), non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR <60 ml/min/1.73m² and 54.3% for proteinuria ≥1+). Lower eGFR (<60 vs. ≥60 ml/min/1.73m²) was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24–1.78]) and non-CVD/non-cancer causes (1.78 [1.54–2.05]). The risk of cancer mortality only reached significance at eGFR <45 ml/min/1.73m² when eGFR 45–59 ml/min/1.73m² was set as a reference (1.62 [1.10–2.39]). High proteinuria (dipstick ≥1+ vs. negative/trace) was consistently associated with mortality due to CVD (1.93 [1.66–2.25]), cancer (1.49 [1.32–1.68]), and other causes (2.19 [1.96–2.45]). Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis.</p><p>Conclusion</p><p>Low eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD, particularly when proteinuria is present.</p></div

Impact of Socioeconomic Status on Mortality and Readmission in Patients With Heart Failure With Reduced Ejection Fraction: The ARIC Study

Background Low socioeconomic status (SES) is associated with a higher risk of heart failure (HF). The contribution of individual and neighborhood SES to the prognosis and quality of care for HF with reduced ejection fraction is not clear yet has important implications. Methods and Results We examined 728 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 78.2 years; 34% Black participants; 46% women) hospitalized with HF with reduced ejection fraction (ejection fraction <50%) between 2005 and 2018. We assessed associations between education, income, and area deprivation index with mortality and HF readmission using multivariable Cox models. We also evaluated the use of guideline‐directed medical therapy (optimal: ≥3 of ß‐blockers, mineralocorticoid receptor antagonist, angiotensin‐converting enzyme inhibitors, or angiotensin receptor blockers; acceptable: at least 2) at discharge. During a median follow‐up of 3.2 years, 58.7% were readmitted with HF, and 74.0% died. Low income was associated with higher mortality (hazard ratio [HR], 1.52 [95% CI, 1.14–2.04]) and readmission (HR, 1.45 [95% CI, 1.04–2.03]). Similarly, low education was associated with mortality (HR, 1.27 [95% CI, 1.01–1.59]) and readmission (HR, 1.62 [95% CI, 1.24–2.12]). The highest versus lowest area deprivation index quartile was associated with readmission (HR, 1.69 [95% CI, 1.11–2.58]) but not necessarily with mortality. The prevalence of optimal guideline‐directed medical therapy and acceptable guideline‐directed medical therapy was 5.5% and 54.4%, respectively, but did not significantly differ by SES. Conclusions Among patients hospitalized with HF with reduced ejection fraction, low SES was independently associated with mortality and HF readmission. A targeted secondary prevention approach that focuses intensive efforts on patients with low SES will be necessary to improve outcomes of those with HF with reduced ejection fraction

Hazard ratios (95%CI) for cause-specific mortality by dipstick proteinuria in Korean Heart Study.

<p>Hazard ratios (95%CI) for cause-specific mortality by dipstick proteinuria in Korean Heart Study.</p

Age-standardized mortality rate (per 1000 person-years) by eGFR.

<p>Age-standardized mortality rate (per 1000 person-years) by eGFR.</p

Adjusted hazard ratios of cause-specific mortality for eGFR<60 ml/min/1.73m² (vs.≥60).

<p>Adjusted hazard ratios of cause-specific mortality for eGFR<60 ml/min/1.73m² (vs.≥60).</p