Serum p-cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients

Introduction

Previous studies have shown that serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were significantly related to clinical outcomes in patients on hemodialysis (HD). However, evidence for the relationship in elderly HD patients remains scarce. We explore whether the two toxins can predict clinical outcomes in elderly HD patients.

Material and methods

Fifty stable HD patients more than 65 years old were enrolled from a single medical center. Serum total and free PCS, IS levels and biochemistry were measured concurrently. The clinical outcomes including cardiovascular events and all-cause mortality were analyzed after 38-month follow-up.

Results

Univariate Cox proportional hazard ratio analysis revealed that cardiovascular events were associated with gender (p = 0.02), diabetes (p < 0.01), calcium (p = 0.01), total PCS (p < 0.01), free PCS (p < 0.01) and total IS (p = 0.05). Multivariate analysis showed that diabetes (p = 0.01), total PCS (p = 0.01) and free PCS (p = 0.04) were related to cardiovascular events. For all-cause mortality, only total PCS (p = 0.01) reached significance after adjusting other confounding factors. However, Kaplan-Meier analysis indicated that free PCS (p = 0.02) and total PCS (p < 0.01) were significantly associated with cardiovascular events and total PCS (p = 0.048) was related to all-cause mortality during 38-month follow-up.

Conclusions

Our results indicate that total PCS is a valuable marker in predicting cardiovascular event and all-cause mortality in elderly HD patients.     

脱氢表雄酮及其硫酸盐的生理及与动脉粥样硬化的关系

脱氢表雄酮（dehydroepiandrosterone,DHEA）及其硫酸盐（dehydroepiandrosterone sulfate,DHEAS）是人类肾上腺分泌的最主要的类固醇激素,其在血浆中的含量也最高。DHEA在胎儿时期受胎盘促肾上腺皮质激素释放激素的影响,产生大量的DHEA,出生后迅速下降,出生后5年内水平很低,然后开始增加,到青春期到达高峰。之后随着年龄的增长明显下降。到90岁下降接近90％。因此它被称为“青春激素”。在成年人中,血浆DHEAS的水平是雄激素的100～500倍,是雌激素的1000～10000倍。     

APOE-related mortality: effect of dementia, cardiovascular disease and gender

Allele-frequency comparisons between younger and older populations suggest an effect of apolipoprotein E gene (APOE) on mortality, not consistently confirmed by longitudinal data. Our aim was to assess the effect of APOE on survival taking into account the possible contribution of Alzheimer's disease, other dementias, ischemic heart- and cerebrovascular disease (IHCD). In a community-based longitudinal study, the Kungsholmen Project, 75+ year-old individuals (n=1094) were examined, and followed for 18 years. An increased mortality-risk of 22% in those with the epsilon4 allele was detected; whereas a 28% decreased mortality-risk was detected in those with the epsilon2 allele compared to those with the epsilon3epsilon3 genotype. IHCD adjustment did not change the mortality-risk in those with the epsilon4 allele or the epsilon2 allele. Dementia accounted for the majority of the increased mortality-risk associated with the epsilon4 allele, but the protective effect of the epsilon2 allele remained. Both effects of the epsilon4 allele and the epsilon2 allele were strongly modified by gender. A 49% elevated risk for death in men was related to the epsilon4 allele, and a 36% decreased mortality-risk was found in women with the epsilon2 allele. These findings suggest different roles for the APOE alleles in survival by gender in old age.     

A prospective study of sleep duration and mortality risk in women

STUDY OBJECTIVES: It is commonly believed that 8 hours of sleep per night is optimal for good health. However, recent studies suggest the risk of death is lower in those sleeping 7 hours. We prospectively examined the association between sleep duration and mortality in women to better understand the effect of sleep duration on health. DESIGN: Prospective observational study. SETTING: Community-based. PARTICIPANTS: Women in the Nurses Health Study who answered a mailed questionnaire asking about sleep duration in 1986. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Vital status was ascertained through questionnaires, contact with next of kin, and the National Death Index. During the 14 years of this study (1986-2000), 5409 deaths occurred in the 82,969 women who responded to the initial questionnaire. Mortality risk was lowest among nurses reporting 7 hours of sleep per night. After adjusting for age, smoking, alcohol, exercise, depression, snoring, obesity, and history of cancer and cardiovascular disease, sleeping less than 6 hours or more than 7 hours remained associated with an increased risk of death. The relative mortality risk for sleeping 5 hours or less was 1.15 (95% confidence interval [CI], 1.02-1.29) for 6 hours, 1.01 (95% CI, 0.94-1.08), for 7 hours, 1.00 (reference group), for 8 hours, 1.12 (95% CI, 1.05-1.20), and for 9 or more hours 1.42 (95% CI, 1.27-1.58). CONCLUSIONS: These results confirm previous findings that mortality risk in women is lowest among those sleeping 6 to 7 hours. Further research is needed to understand the mechanisms by which short and long sleep times can affect health.     

Stress-limiting effect of dehydroepiandrosterone sulfate and its mechanism

Dehydroepiandrosterone sulfate prevented the increase in corticosterone level in rats induced by repeated exposure to stress. The -opioid receptor blocker naltrexone administered in a dose of 0.1 mg/kg 20 min before treatment with dehydroepiandrosterone sulfate abolished the effect of this agent. Dehydroepiandrosterone sulfate and naltrexone had no effect on rats after acute stress.     

A review of low-density lipoprotein cholesterol,treatment strategies,and its impact on cardiovascular disease morbidity and mortality

Cardiovascular (CV) disease is a leading cause of death worldwide, accounting for approximately 31.4% of deaths globally in 2012. It is estimated that, from 1980 to 2000, reduction in total cholesterol accounted for a 33% decrease in coronary heart disease (CHD) deaths in the United States. In other developed countries, similar decreases in CHD deaths (ranging from 19%–46%) have been attributed to reduction in total cholesterol. Low-density lipoprotein cholesterol (LDL-C) has now largely replaced total cholesterol as a risk marker and the primary treatment target for hyperlipidemia. Reduction in LDL-C levels by statin-based therapies has been demonstrated to result in a reduction in the risk of nonfatal CV events and mortality in a continuous and graded manner over a wide range of baseline risk and LDL-C levels. This article provides a review of (1) the relationship between LDL-C and CV risk from a biologic, epidemiologic, and genetic standpoint; (2) evidence-based strategies for LDL-C lowering; (3) lipid-management guidelines; (4) new strategies to further reduce CV risk through LDL-C lowering; and (5) population-level and health-system initiatives aimed at identifying, treating, and lowering lifetime LDL-C exposure.     

Functional impairments of human red cells,induced by dehydroepiandrosterone sulfate

A study has been made on the incorporation of dehydroepiandrosterone sulfate (DHAS), one of the most abundant adrenal C-19 steroids, into human red cells, and of the resulting effects on red cell functions. 1. DHAS was incorporated into red cell membrane mainly by a partition mechanism: The apparent partition constant was small ([DHAS]cell/[DHAS]free = 1.34), indicating that DHAS in red cells would be easily removed by dilution. 2. At least part of the DHAS taken up was apparently bound to band 3 protein and thereby was able to inhibit the exchange of intracellular and extracellular SO4(2-) (Ki = 70 micro M). 3. Using a fatty acid spin label, it was established that the presence of DHAS in lipid bilayer of the membrane increased the acyl chain motion in the middle portion of the membrane. 4. DHAS induced echinocytosis of red cells. It is suggested that the increase in the viscosity of red cell suspension, the decreased deformability and the decrease in the deoxygenation rate of hemoglobin in the presence of DHAS probably reflect the presence of echinocytes. 5. In the presence of plasma proteins, the incorporation of DHAs into red cells was remarkably suppressed.     

Adults with cardiovascular disease who help others: a prospective study of health outcomes

Little is known about the health impact of helping behaviors among individuals with high-risk chronic diseases such as cardiovascular disease (CVD). Using a nationally representative, longitudinal survey, we examined the subsequent health of adults with CVD (n = 4,491) who spent time providing non-paid assistance to family and friends outside of their households compared with those who had provided no assistance. After both adjusting for baseline characteristics and using propensity score matching methods, spending up to 200 h over the prior 12 months helping others was associated with lower odds of experiencing a new CVD event or dying in the subsequent 2 years. Providing up to 100 h of assistance was associated with reporting fewer depressive symptoms. This threshold effect raises the question of whether assistance beyond a certain number of hours may impose a burden that mitigates health benefits from helping others. Health care providers could play an important role exploring ways that patients with CVD can provide beneficial levels of assistance to others in their own social networks or communities, thereby possibly also improving their own health.     

Dietary intakes of monounsaturated fatty acids and risk of mortality from all causes,cardiovascular disease and cancer: A systematic review and dose-response meta-analysis of prospective cohort studies

BackgroundFindings on the link between dietary intakes of monounsaturated fatty acids (MUFA) and risk of mortality are conflicting. This study aimed to summarize existing literature regarding the association between MUFA intake and risk of mortality from all causes, cardiovascular diseases (CVDs), and cancer.MethodsPubMed, Scopus, and ISI Web of Science was systematically searched up to December 2020. Prospective cohort studies which investigated MUFA intake in relation to mortality from all causes, CVD, or cancer were eligible for this systematic review. Publications that had reported risk ratios (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) as effect size, were considered.ResultsA total of 17 prospective cohort studies were included. These studies included 1022,321 participants aged ≥ 20 years in total, and 191,283 all-cause deaths, 55,437 CVD deaths, and 64,448 cancer deaths were totally reported. Combining 15 effect sizes from 11 studies, MUFA intake was inversely associated with risk of all-cause mortality (RR: 0.94; 95% CI: 0.90, 0.98; I² =55.5; P = 0.005). Based on 17 effect sizes from 11 studies, we found no significant association between MUFA intake and risk of CVD mortality (RR: 0.95; 95% CI: 0.89, 1.01; I² =37.0; P = 0.06). Combining 10 effect sizes from 6 studies, MUFA intake was not significantly associated with cancer mortality (RR: 0.99; 95% CI: 0.96, 1.03, I² =13.3%, P = 0.32). Also, an additional 5% of energy from MUFA was associated with a 3% reduced risk of all-cause mortality (RR: 0.97; 95%CI: 0.96, 0.98), but not with CVD (RR: 0.98; 95%CI: 0.95, 1.01) and cancer mortality (RR: 0.99; 95%CI: 0.97, 1.01).ConclusionsMUFA intake was found to be inversely associated with risk of all-cause mortality. However, no link was found between MUFA consumption and mortality from CVD or cancer.     

Dietary potassium and stroke-associated mortality. A 12-year prospective population study

Hypertension is the most important known risk factor for stroke. Clinical, experimental, and epidemiologic evidence suggests that a high dietary intake of potassium is associated with lower blood pressure. In hypertensive rats, a high intake of potassium is reported to protect against stroke, even though blood pressure is not affected. We examined the relation between the 24-hour dietary potassium intake at base line and subsequent stroke-associated mortality in a population-based cohort of 859 men and women (aged 50 to 79 years) in Southern California. After 12 years, 24 stroke-associated deaths had occurred. The relative risks of stroke-associated mortality in the lowest tertile of potassium intake, as compared with that in the top two tertiles combined, were 2.6 (P = 0.16) in men and 4.8 (P = 0.01) in women. In multivariate analyses, a 10-mmol increase in daily potassium intake was associated with a 40 percent reduction in the risk of stroke-associated mortality (P less than 0.001). This effect was independent of other dietary variables, including the intake of calories, fat, protein, fiber, calcium, magnesium, and alcohol. The effect was also apparently independent of known cardiovascular risk factors, including age, sex, blood pressure, blood cholesterol level, obesity, fasting blood glucose level, and cigarette smoking. These findings support the hypothesis that a high intake of potassium from food sources may protect against stroke-associated death.     

HLA*A2 confers mortality risk for cardiovascular disease in Pimans

A sample of 1465 full heritage Piman Indians from Arizona were typed for the serological antigens of the HLA class I loci and then incorporated into a survival study that ended December 31, 1991. The total follow-up time was 11,749 person-years with an average of 8.0 years per person. During the study 298 persons died, 54 from cardiovascular disease (CVD). Allele HLA*A2 conferred a 4.94 fold rate for death from CVD (95% C.I. 1.91 – 12.77). When controlled for the potential confounding variables, cholesterol, mean blood pressure, smoking, body mass index, rheumatoid factor titer, and nephropathy, the mortality rate ratio (MRR) was 5.42 (95% C.I. 1.98 – 14.82). There was no statistically significant association of mortality with other HLA-A or HLA-B alleles, or for causes of death not related to cardiovascular disease.     

Autopsy study in the analysis of cardiovascular mortality

The frequency of using autopsy to verify the cardiovascular causes of death was studied in typical regions of Russia. One thousand and sixty deaths from circulatory system diseases were analyzed among a representative sample of 285,736 subjects. Death occurred outside health care facilities in 88% of the analyzed cases; nevertheless, autopsy was made only in 28.3%. Moreover, autopsy was carried out in all cases of less than 40-year-old males and less than 50-year-old females who had died from suspected cardiovascular diseases. The proportion of notified cardiovascular mortality increased in the structure of overall mortality and the rate of autopsy-verified diagnosis decreased with advanced age. To obtain valid information on cardiovascular mortality rates is limited due to low autopsy rates primarily in cases of death outside health care facilities, particularly among elderly and senile persons, despite the fact that it is these fatal cases that constitute the bulk of registered cardiovascular mortality.     

Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease

To determine the associations of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol with mortality from coronary heart disease and cardiovascular disease, we studied 2541 white men who were 40 to 69 years old at base line and followed them for an average of 10.1 years. Seventeen percent had some manifestation of cardiovascular disease at base line, whereas the others did not. Among the men who had cardiovascular disease at base line, we found, after multivariate adjustment, that those with "high" blood cholesterol levels (above 6.19 mmol per liter) had a risk of death from cardiovascular disease, including coronary heart disease, that was 3.45 times higher (95 percent confidence interval, 1.63 to 7.33) than that for men with "desirable" blood cholesterol levels (below 5.16 mmol per liter). The corresponding hazard ratios were 5.92 (95 percent confidence interval, 2.59 to 13.51) for LDL cholesterol levels above 4.13 mmol per liter as compared with those below 3.35 mmol per liter, and 6.02 (95 percent confidence interval, 2.73 to 13.28) for HDL cholesterol levels below 0.90 mmol per liter as compared with those above 1.16 mmol per liter. All three lipid levels were also significant predictors of death from coronary heart disease alone (P less than 0.005). Total cholesterol and LDL cholesterol levels were also significant predictors of death from cardiovascular and coronary heart disease in men without preexisting cardiovascular disease, although at a lower level of absolute risk of death. Thus, the 10-year risk of death from cardiovascular disease for a man with preexisting cardiovascular disease increased from 3.8 percent to almost 19.6 percent with increasing levels of total cholesterol from "desirable" to "high," whereas the corresponding risk for a man who was free of cardiovascular disease at base line increased from 1.7 percent to 4.9 percent. Our findings suggest that total, LDL, and HDL cholesterol levels predict subsequent mortality in men 40 to 69 years of age, especially those with preexisting cardiovascular disease.     

Geographic variation in cardiovascular disease mortality in US blacks and whites

Cardiovascular disease mortality rates have dropped significantly over the past several decades, but a shift has occurred over time in the geographic patterns of both coronary heart disease (CHD) and stroke mortality. This article describes these patterns and discusses how they vary by sex, race, age, and over time. Death certificate information for Health Service Areas (HSAs) in 1988-1992 was used to analyze the geographic patterns of CHD and stroke death rates by race, sex, and age. Changes in these patterns from 1979-1993 also were examined. In 1988-1992, considerable geographic variation in both CHD and stroke mortality was demonstrated for each sex and race group. Coronary heart disease rates were particularly high in the lower Mississippi valley and Oklahoma for all four groups, in the Ohio River valley and New York for whites, and to a lesser extent for blacks. Areas of high rates among whites in the Carolinas resemble stroke mortality patterns. There were greater differences by racial group than by gender, by the definition of heart disease. Over time, rates have declined for both CHD and stroke, but regional differences in the rates of change give the appearance of a southwesternly movement of high heart disease rate clusters and a breakup of the "Stroke Belt." Further research is needed to elucidate the cause of regional variation in CHD and stroke mortality. Similar geographic patterns of high rates of CHD and stroke in the southeastern United States may reflect common risk factors. This knowledge can be used to help develop appropriate interventions to target these high-rate areas in the Mississippi and Ohio River valleys.