Association of Urine Albumin-Creatinine Ratio and Cystatin C-Based Estimated GFR with Outcomes in Patients with Ischemic Stroke.

BACKGROUND/AIMS: Data about the independent and combined effects of cystatin C-based estimated glomerular filtration rate (eGFRcys) and albuminuria on the risk of poor outcome in stroke patients are limited. The aim was to elucidate how these two renal markers affect the clinical outcomes after ischemic stroke separately and jointly. METHODS: The study subjects consisted of 10,197 patients with ischemic stroke from the third China National Stroke Registry. The study outcomes were all-cause mortality, poststroke disability, recurrence of stroke, and cardiocerebral vascular disease (CVD) composite events. Cox proportional hazard models and multivariable logistic regression model were applied to evaluate the effects of eGFRcys and urine albumin-creatinine ratio (ACR) on these outcomes. RESULTS: Both reduced eGFRcys and increased ACR were independently associated with higher incidences of all-cause death and poststroke disability (p < 0.01). Mildly decreased eGFRcys (60-89 mL/min/1.73 m2) is associated with increased risk of all-cause death and poststroke disability in the presence of high-normal ACR (10-29 mg/g). Patients with both eGFRcys <45 mL/min/1.73 m2 and ACR ≥30 mg/g at baseline had a 6.8-fold risk for all-cause mortality and 3.6-fold risk for poststroke disability, compared with patients with eGFRcys of 90-119 mL/min/1.73 m2 and ACR <10 mg/g. In addition, increased ACR was associated with recurrent stroke and CVD composite event, while reduced eGFRcys showed no relationship with these outcomes. CONCLUSIONS: Both decreased eGFRcys and albuminuria are independent risk factors for all-cause death and poststroke disability. Combining the two markers is useful for improving risk stratification even in those without chronic kidney disease.

Mass spectrometry-based urinary metabolomics for the investigation on the mechanism of action of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves against ischemic stroke in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) can treat ischemic, neurasthenia, and hypertension diseases. However, only few studies have been conducted on the mechanism of action of ESL for ischemic disease treatment. AIM OF THE STUDY: This study aimed to discover the potential biomarkers in the rats caused by ischemic stroke and build a gene-enzyme-biomarker network to explore the mechanism of ESL treatment on ischemic stroke further. MATERIALS AND METHODS: The urinary metabolomics strategy was developed by combining UPLC-Q-TOF/MS with multivariate data analysis. The gene-enzyme-biomarker network was built by Cytoscape 3.6.0 on the basis of the potential biomarkers filtered out via urinary metabolomic analysis. Then, the potential target enzymes of ESL in the treatment of ischemic stroke were selected for further validation analysis via the ELISA kits. RESULTS: A total of 42 biomarkers associated with ischemic stroke have been identified, among which 38 species can be adjusted by ESL, including 5'-methylthioadenosine, prostaglandin A2, l-methionine, aldosterone, 11b-hydroxyprogesterone, prostaglandin E3, dehydroepiandrosterone, taurine, 5-methoxyindoleacetate, and p-cresol glucuronide. These biomarkers were involved in several metabolic pathways, including taurine and hypotaurine, arachidonic acid, cysteine and methionine, steroid hormone biosynthesis, tryptophan, and tyrosine metabolism pathways. The gene-enzyme-biomarker network was built, and three predicted target proteins, including cyclooxygenase-2 (COX-2), monoamine oxidase (MAO), and nitric oxide synthase (NOS), were selected as the potential target enzymes for ESL in ischemic stroke treatment. CONCLUSIONS: All results showed that ESL can play a therapeutic role in treating ischemic stroke through different pathways. This study will provide an overall view of the mechanism underlying the action of ESL against ischemic stroke.

Urinary cadmium concentration and the risk of ischemic stroke.

OBJECTIVES: To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. METHODS: A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. RESULTS: The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) µg/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). CONCLUSIONS: Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure.

Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long-Term Outcome After Cardiac Surgery.

BACKGROUND: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome. METHODS AND RESULTS: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11-dehydrothromboxane B2 (11-dhTXB2), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, and death alone. 11-dhTXB2 measured 3 days after surgery did not independently predict outcome, whereas 11-dhTXB2 >450 pg/mg creatinine measured 6 months after surgery predicted the composite end point (adjusted hazard ratio, 1.79; P=0.02) and death (adjusted hazard ratio, 2.90; P=0.01) at 5 years compared with lower values. Additional modeling revealed 11-dhTXB2 measured early after surgery associated with several markers of inflammation, in contrast to 11-dhTXB2 measured 6 months later, which highly associated with oxidative stress. CONCLUSIONS: Long-term nonplatelet thromboxane generation after coronary artery bypass graft surgery is a novel risk factor for 5-year adverse outcome, including death. In contrast, nonplatelet thromboxane generation in the early postoperative period appears to be driven predominantly by inflammation and did not independently predict long-term clinical outcome.

Recent Progress in Analytical Methods for Determination of Urinary 3-Hydroxypropylmercapturic Acid, a Major Metabolite of Acrolein.

3-Hydroxypropylmercapturic acid (3-HPMA), a major metabolite of acrolein in urine, has been recognized as a noninvasive biomarker of exposure to cigarette smoke. Since acrolein is formed endogenously from polyamines and is also formed during oxidative stress and aggravates tissue damage by changing protein activity through its conjugation in pathological lesions, it is thought that the urinary 3-HPMA level is useful as a biomarker to monitor the severity of several diseases related to acrolein. To study the correlation between 3-HPMA and disease severity, it is important to understand the properties of analytical methods for determination of 3-HPMA. In this article, we summarize the analytical methods for determination of urinary 3-HPMA and discuss the utility of 3-HPMA as one of the biomarkers for the diagnosis of brain infarction.

Diagnostic Yield of Universal Urine Toxicology Screening in an Unselected Cohort of Stroke Patients.

BACKGROUND: Illicit drug use increases the risk of cerebrovascular events by a variety of mechanisms. A recent report suggested that universal urine toxicology (UTox) screening of patients with stroke may be warranted. We aimed to evaluate the diagnostic yield of urine drug screening among unselected patients admitted with acute stroke or transient ischemic attack (TIA). METHODS: Using a single-center prospective study design, we evaluated consecutive patients with acute ischemic stroke, TIA, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) over one year. Urine samples were collected within 48 hours of admission and analyzed for common classes of abused drugs. Prevalence of positive UTox screening was determined. We evaluated whether baseline demographics and clinical factors were associated with UTox results. RESULTS: Of 483 eligible patients (acute ischemic stroke 66.4%; TIA 18.8%; ICH 7.7%; SAH 7.0%), 414 (85.7%) completed UTox screening. The mean (standard deviation) age was 65.1 (15.6) years, 52.7% were male, and 64.3% were Caucasian. Twenty-two (4.6%) patients had positive screening-cannabinoids were detected in 13 cases (3.1%), cocaine in 5 cases (1.2%), amphetamines in 1 case, and phencyclidine in 1 case. The highest yield (14.1%) was observed in patients < 60 years old with history of tobacco use while it was < 5% in the remaining subgroups (p<0.01). CONCLUSIONS: Consistent with current guidelines, a selective approach to UTox screening should be pursued in acute stroke evaluation. The highest diagnostic yield is likely to be for cannabinoids and cocaine testing in younger patients with a history of concurrent tobacco use.

Dietary isoflavones, urinary isoflavonoids, and risk of ischemic stroke in women.

BACKGROUND: Hormone therapy has been shown to increase risk of ischemic stroke in women. Plant-derived estrogens, particularly soy isoflavones, are known to have some estrogenic effects and have been marketed as natural alternatives to hormone therapy. Concerns have been raised about whether high isoflavone exposure may be related to ischemic stroke risk as well. OBJECTIVE: We examined the dietary intake of isoflavones and the urinary excretion of isoflavonoids in relation to risk of ischemic stroke in women. DESIGN: A prospective cohort study was conducted in 66,832 Chinese women (aged 40-70 y) who had no cardiovascular disease or cancer at baseline. Usual dietary intakes were assessed via in-person interviews with the use of a validated food-frequency questionnaire. Incident strokes were ascertained during follow-up home visits and confirmed by medical records. We also conducted a nested case-control study in postmenopausal women who had never used hormone therapy, including 1422 incident ischemic stroke cases and 1422 controls individually matched by age, date and time of urine sample collection, time since last meal, and use of antibiotics. Urinary isoflavonoids were measured with the use of high-performance liquid chromatography coupled with mass spectrometry. RESULTS: During a mean follow-up of 10 y, 3110 incident ischemic strokes were verified. Dietary isoflavone intake was associated with increased risk of ischemic stroke; multivariable-adjusted HRs from lowest to highest quintiles were 1.00, 1.05, 1.10, 1.11, and 1.24, respectively (95% CI: 1.08, 1.42; P-trend = 0.002). In the case-control study, a similar positive association was observed for dietary isoflavones, but no significant associations were shown for the urinary isoflavonoid concentration [OR: 1.01 (95% CI: 0.77, 1.32) for comparison of extreme quintiles]. CONCLUSIONS: A habitually high intake of soy isoflavones may be associated with a modest but significant increase in risk of ischemic stroke in women. However, no association was shown for the urinary excretion of isoflavonoids.

Stroke-induced immune depression-a randomized case control study in Kashmiri population of North India.

BACKGROUND: Stroke leads to transient immunedepression, which leads to increased incidence of poststroke infections. Because infection is one of the most common causes of increased mortality in patients with stroke, this study was undertaken to document immunedepression after stroke in our population. METHODS: A case-controlled study wherein 39 patients with acute ischemic stroke in the age group of 18 and 60 years without any evidence of previous immunedepression were included. Interleukin 6 (IL-6) and interleukin 10 (IL-10) levels were checked in plasma in both the groups on day 3 and day 45. Also Cortisol and epinephrine levels were checked in the urine samples collected on day 3 and day 8. RESULTS: No significant difference was seen between the IL-6 and the IL-10 levels in samples collected on day 3 between the controls and cases, whereas Cortisol and norepinephrine were significantly raised in samples collected on day 3 in cases who developed infection as compared with controls. CONCLUSIONS: The higher levels of urinary cortisol and norepinephrine were observed in patients with stroke who developed infections, which indirectly reflected increased amount of stroke related stress. Furthermore, the levels of plasma IL-6 and IL-10 were also elevated in the same group of patients, which means transformation of immunecompetence to immunedepression, which is responsible for higher mortality. Subsequently on recovery from infection the plasma levels of interleukins and urinary cortisol and norepinephrine did not show any difference, which indirectly means recovery of the immune system on recovery from acute stage of stroke. Mortality in the patients with infection was increased than controls.

Cannabis, ischemic stroke, and transient ischemic attack: a case-control study.

BACKGROUND AND PURPOSE: There is a temporal relationship between cannabis use and stroke in case series and population-based studies. METHODS: Consecutive stroke patients, aged 18 to 55 years, who had urine screens for cannabis were compared with a cohort of control patients admitted to hospital without cardiovascular or neurological diagnoses. RESULTS: One hundred sixty of 218 (73%) ischemic stroke/transient ischemic attack patients had urine drug screens (100 men; mean [SD] age, 44.8 [8.7] years). Twenty-five (15.6%) patients had positive cannabis drug screens. These patients were more likely to be men (84% versus 59%; χ2: P=0.016) and tobacco smokers (88% versus 28%; χ2: P<0.001). Control urine samples were obtained from 160 patients matched for age, sex, and ethnicity. Thirteen (8.1%) control participants tested positive for cannabis. In a logistic regression analysis adjusted for age, sex, and ethnicity, cannabis use was associated with increased risk of ischemic stroke/transient ischemic attack (odds ratio, 2.30; 95% confidence interval, 1.08-5.08). However after adjusting for tobacco use, an association independent of tobacco could not be confirmed (odds ratio, 1.59; 95% confidence interval, 0.71-3.70). CONCLUSIONS: This study provides evidence of an association between a cannabis lifestyle that includes tobacco and ischemic stroke. Further research is required to clarify whether there is an association between cannabis and stroke independent of tobacco. CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au. Unique identifier: ACTRN12610000198022.

Urine toxicology screening in an urban stroke and TIA population.

OBJECTIVE: We sought to determine the rate of urine toxicology screening, differences in testing, and outcomes among patients with stroke and TIA presenting to a tertiary care emergency department. METHODS: In this retrospective cohort study, patients admitted with stroke or TIA to a single tertiary care stroke center between June 2005 and January 2007 were identified through a stroke database. Factors that predicted urine toxicology screening of patients and a positive test, and discharge outcomes of patients based on toxicology result were analyzed. Stroke severity, treatment with tissue plasminogen activator, discharge status, and stroke etiology were compared between toxicology positive and negative patients. RESULTS: A total of 1,024 patients were identified: 704 with ischemic stroke, 133 with intracerebral hemorrhage, and 205 with TIA. Urine toxicology screening was performed in 420 patients (40%); 11% of these studies were positive for cocaine (19% younger than 50 years and 9% 50 years or older). Factors that significantly predicted the performance of a urine toxicology screen were younger age (<50 years) and black race (<0.001). Positive toxicology screens occurred in a broad range of patients. There were no significant differences in admission NIH Stroke Scale score, stroke etiology, and discharge status between toxicology-positive and -negative patients. CONCLUSIONS: In this study, patients with stroke and TIA who were young and black were more likely to have urine toxicology screening. Eleven percent of all tested patients (and 9% of patients 50 years or older) were positive for cocaine. To avoid disparities, we suggest that all stroke and TIA patients be tested.

The usefulness of rapid point-of-care creatinine testing for the prevention of contrast-induced nephropathy in the emergency department.

BACKGROUND: Renal dysfunction is the most important factor to consider when predicting a patient's risk of developing contrast-induced nephropathy (CIN). Measurement of creatinine (Cr) via rapid point-of-care blood urea nitrogen/creatinine testing (POCT-BUN/Cr) to determine CIN risk could potentially reduce the time required to achieve an accurate diagnosis and to initiate and complete treatment in the emergency department (ED). The aim of our study was to compare the results of POCT-BUN/Cr and reference laboratory tests for BUN and serum Cr. MATERIALS AND METHODS: A retrospective analysis of suspected stroke patients who presented between November 2009 and November 2010, and had BUN and Cr levels measured by POCT-BUN/Cr, and the reference laboratory tests performed with the blood sample which was transferred to the central laboratory by an air-shoot system. Two assays were conducted on the whole blood (POCT) and serum (reference) by trained technicians. The time interval from arrival at the ED to reporting of the results was assessed for both assays via a computerised physician order entry system. RESULTS: The mean standard deviation (SD) interval from arrival at the ED to reporting of the results was 11.4 (4.9) min for POCT-BUN/Cr and 46.8 (38.5) min for the serum reference laboratory tests (p<0.001). Intra-class correlation coefficient (ICC) analysis demonstrated a high level of agreement (the consistency agreement) between POCT and the serum reference tests for both BUN (ICC=0.914) and Cr (ICC=0.980). CONCLUSIONS: This study suggests that POCT-BUN/Cr results correlate well with those of serum reference tests in terms of BUN and Cr levels and, in turn, predicting CIN. POCT-BUN/Cr is easily performed with a rapid turnaround time, suggesting its use in the ED may have substantial clinical benefit.

Urinary microalbumin as a risk factor for ischaemic stroke.

Microalbuminuria (MA), a microvascular irregularity of the blood - urine interface within kidney glomeruli, may reflect the renal sign of global endothelial dysfunction, and has been associated with an elevated risk of serious cardiovascular events including stroke. This case-control study was carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2008 to December 2009. This relationship appears graded with higher levels of microalbuminuria being independently associated with a greater magnitude of vascular risk over time. We studied 60 patients of ischemic stroke with in 4 weeks of onset of symptoms and performed a case control study for MA by spot urinalysis. The incidence of microalbuminuria was 31.7% of the patients compared with 8.3% of the controls. Of all the traditional risk factors for stroke - age, male gender, hypertension, diabetes, dyslipidemia, smoking showed a positive correlation with the presence of MA (p<0.05). The effect of microalbuminuria and subtypes of ischemic stroke was observed that small vessels stroke (lacunar infract) were more (70%) than large vessels stroke (30%) and effect of microalbuminuria 21.67% higher in small vessels stroke than large vessels stroke. The presence of microalbuminuria appears to independently predict proper clinical outcome following acute stroke.

Inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid, an acrolein-glutathione metabolite.

BACKGROUND: We found previously that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good biomarkers for stroke. The aim of this study was to test whether 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, was increased in the urine of stroke patients. METHODS: The level of 3-HPMA in urine was measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Stroke (78 subjects) was divided into 52 cerebral infarction (CI) and 26 cerebral hemorrhage (CH) on the basis of clinical information including brain imaging. RESULTS: A major acrolein derivative in urine is 3-HPMA. Being different from the results of PC-Acro in plasma, 3-HPMA in urine decreased following stroke. The median value of µmol 3-HPMA/g creatinine (Cre) for 90 control subjects was 2.83, while that for 78 stroke patients was 1.56. The degree of the decrease in 3-HPMA was similar in both CI and CH patients. Furthermore, the median value of µmol 3-HPMA/g Cre in 56 patients with lesions ≥ 1cm in diameter (1.39) was significantly lower than that in 20 patients with lesion <1cm in diameter (2.16). CONCLUSION: Inverse correlation between stroke and urinary 3-HPMA was observed. The results suggest that stroke is aggravated when nervous system tissues have a reduced level of glutathione.

Albuminuria and the risk of incident stroke and stroke types in older adults.

BACKGROUND: The kidney biomarker that best reflects risk of stroke is unknown. We sought to evaluate the association of stroke with 3 kidney biomarkers: albuminuria, cystatin C, and glomerular filtration rate. METHODS: These 3 biomarkers were determined in 3,287 participants without history of stroke from the Cardiovascular Health Study, a longitudinal cohort study of men and women age 65 years and older from 4 US communities. The biomarkers were albuminuria ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up between 1996 and 2006. RESULTS: A total of 390 participants had an incident stroke: 81% ischemic, 12% hemorrhagic, and 7% unclassified. In adjusted Cox regression models, UACR was more strongly related to any stroke, ischemic stroke, and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any stroke comparing the top to bottom quintile of UACR was 2.10 (95% confidence interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95% CI 0.91-1.84) and for cystatin C was 1.22 (95% CI 0.85-1.74). When considering clinically relevant categories, elevated UACR was associated with increased hazard of any stroke and ischemic stroke regardless of eGFR or cystatin C categories. CONCLUSIONS: UACR was the kidney biomarker most strongly associated with risk of incident stroke. Results in this elderly cohort may not be applicable to younger populations. These findings suggest that measures of glomerular filtration and permeability have differential effects on stroke risk.

Cadmium exposure in association with history of stroke and heart failure.

BACKGROUND: It is unclear whether environmental cadmium exposure is associated with cardiovascular disease, although recent data suggest associations with myocardial infarction and peripheral arterial disease. OBJECTIVE: The objective of this study was to evaluate the association of measured cadmium exposure with stroke and heart failure (HF) in the general population. METHODS: We analyzed data from 12,049 participants, aged 30 years and older, in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) for whom information was available on body mass index, smoking status, alcohol consumption, and socio-demographic characteristics. RESULTS: At their interviews, 492 persons reported a history of stroke, and 471 a history of HF. After adjusting for demographic and cardiovascular risk factors, a 50% increase in blood cadmium corresponded to a 35% increased odds of prevalent stroke [OR: 1.35; 95% confidence interval (CI): 1.12-1.65] and a 50% increase in urinary cadmium corresponded to a 9% increase in prevalent stroke [OR: 1.09; 95% CI: 1.00-1.19]. This association was higher among women [OR: 1.38; 95% CI: 1.11-1.72] than men [OR: 1.30; 95% CI: 0.93-1.79] (p-value for interaction=0.05). A 50% increase in blood cadmium corresponded to a 48% increased odds of prevalent HF [OR: 1.48; 95% CI: 1.17-1.87] and a 50% increase in urinary cadmium corresponded to a 12% increase in prevalent HF [OR: 1.12; 95% CI: 1.03-1.20], with no difference in sex-specific associations. CONCLUSIONS: Environmental exposure to cadmium was associated with significantly increased stroke and heart failure prevalence. Cadmium exposure may increase these important manifestations of cardiovascular disease.

Fibrates may cause an abnormal urinary betaine loss which is associated with elevations in plasma homocysteine.

PURPOSE: Betaine is an osmolyte, supplies methyl groups, and controls plasma homocysteine. Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations. We suggest there is a connection between fibrate treatment and betaine excretion. METHODS: We identified 32 fibrate-treated patients in several studies (total of 740 subjects) and compared the betaine excretion by these with the excretion by other patients, both in the separate studies and in the combined group. We investigated the correlation of betaine excretion with homocysteine in these groups. RESULTS: Patients taking bezafibrate had higher betaine excretion than patients not taking fibrates, p < 0.00001 in some studies with n < 10. Of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion. Plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate (n = 68, p = 0.043), but the relationship was stronger if patients taking bezafibrate were included (n = 76, p < 0.00001). In elderly (>65 years) subjects with hypertension there was a similar correlation (n = 19, p = 0.047), which was stronger when a subject taking bezafibrate was included (n = 20, p = 0.013). CONCLUSIONS: Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.

Albuminuria, intermittent hyperfiltration and salt wasting in patients with stroke: a pilot study.

OBJECTIVE: To investigate whether different types of stroke influence renal excretion of albumin, major electrolytes and water. MATERIAL AND METHODS: Timed urine collections were started shortly after admission in 5 patients with haemorrhagic stroke (group A), 5 with ischaemic stroke (group Bx), 6 with presumed ischaemic stroke (groups By/z) and 6 with subarachnoid haemorrhage (group C). Albuminuria was also investigated in four patients undergoing elective abdominal surgery. RESULTS: Increased levels of albuminuria were observed in all patients in groups A and B, but were found to decline with observation time and appeared to be related to outcome in group B. In group C, albuminuria was detected in 4 out of 6 patients. Elective surgery did not affect albumin excretion. In a setting with high urinary osmolality, high excretion rates for creatinine, urea, sodium, potassium and large diuresis were intermittently observed in groups A, B and C. None of these patients was in steady-state condition. CONCLUSIONS: Different types of stroke elicit a complex change in renal function which resembles the response to a hypervolaemic and hyperosmolar signal, possibly mediated by a breakdown of renal autoregulation of blood flow in the presence of high vasopressin activity. Acute changes in excretion of albumin might be an indicator of prognosis in stroke. The findings point to the existence of unrecognized pathways between the central nervous system and the kidneys. Further studies on the mechanisms underlying alterations in renal function in stroke and their implication for treatment and outcome are indicated.

Proteinuria and risk for stroke and coronary heart disease during 27 years of follow-up: the Honolulu Heart Program.

BACKGROUND: Urinary protein excretion has been linked to coronary heart disease (CHD); the relationship to stroke is less clear. We assessed whether urine dipstick screening for protein predicted stroke and CHD in the Honolulu Heart Program cohort. METHODS: Prospective, observational study of 6252 Japanese American men in Honolulu aged 45 to 68 years. Proteinuria was detected by means of urine dipstick screening during the first and third examinations. Subjects were classified as having no proteinuria if results were negative at both examinations, transient proteinuria if results were positive at 1 examination, and persistent proteinuria if results were positive at both examinations. Relative risk was derived using those subjects with no proteinuria as the reference. Outcomes were assessed through 27 years. RESULTS: No proteinuria was found in 92.8% of subjects, transient proteinuria in 6.1%, and persistent proteinuria in 1.1%. The age-adjusted incident stroke rates were 3.7, 7.3, and 11.8 per 1000 person-years in subjects with no, transient, or persistent proteinuria, respectively (P<.001). Age-adjusted rates of incident CHD were 9.4, 15.8, and 35.2 events per 1000 person-years, respectively (P<.001). Using Cox proportional hazards models, adjusting for age, body mass index, physical activity, smoking status, cholesterol level, presence of hypertension or diabetes mellitus, and alcohol consumption, the relative risk for 27-year incident stroke was 1.66 (95% confidence interval, 1.21-2.30; P = .002) with transient proteinuria and 2.84 (95% confidence interval, 1.51-5.34; P = .001) with persistent proteinuria, and relative risk for 27-year incident CHD was 1.48 (95% confidence interval, 1.19-1.83; P<.001) with transient proteinuria and 3.72 (95% confidence interval, 2.62-5.27; P<.001) with persistent proteinuria. CONCLUSION: Proteinuria detected at urine dipstick screening independently predicted increased risk for incident stroke and incident CHD over 27 years in this cohort.

Microalbuminuria, cardiovascular risk factors and cardiovascular morbidity in a British population: the EPIC-Norfolk population-based study.

BACKGROUND: Microalbuminuria is independently associated with increased cardiovascular risk and renal function deterioration in diabetes and hypertension, but the clinical relevance of raised albuminuria in the general population is less certain. We examined the prevalence of microalbuminuria and its relationship to cardiovascular risk factors and cardiovascular morbidity in the UK general population. METHODS: Cross-sectional population-based study of 23,964 individuals, aged 40-79 years recruited in 1993-1997 for the EPIC-Norfolk Study. Smoking status, prevalent physician diagnosed diabetes, hypertension, cardiovascular disease and cancer were derived from a health and lifestyle questionnaire. Albumin-to-creatinine ratios were estimated from random spot urine specimens collected at the survey visit, and using these ratios participants were categorized into normoalbuminuria, microalbuminuria (2.5-25 mg/mmol), and macroalbuminuria. RESULTS: The prevalence of microalbuminuria and macroalbuminuria was 11.8% and 0.9% respectively in the total population and significantly higher in women (14.4%) compared with men (8.9%) (P<0.001). Independent determinants of microalbuminuria were age, sex, systolic blood pressure and current smoking. Microalbuminuria was independently associated with cardiovascular morbidity, after adjusting for known cardiovascular risk factors, with odds ratio (95% confidence interval) for prevalent cardiovascular disease of 1.30 (1.12-1.51) in all men and women. CONCLUSION: Microalbuminuria was present in approximately 12% of this population. It was independently associated with cardiovascular risk factors and prevalent cardiovascular disease. Microalbuminuria may be a useful indicator of high absolute cardiovascular risk in the community but prospective data are needed to establish its independent predictive value for future events.