Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: We sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S. METHODS AND RESULTS: Six hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75 ± 17 vs. 85 ± 20 nmol/L [30 ± 7 vs. 34 ± 8 ng/mL], P<0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L [>30 ng/mL], reference group), insufficient (37-75 nmol/L [15-30 ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90-6.34) or deficient (<37 nmol/L [<15 ng/mL]; adjusted OR: 2.56, 95% CI: 1.27-5.19). When modeled as a continuous variable, increased log10 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064-0.96, P=0.02). CONCLUSION: Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.

Vitamin D deficiency may be an independent risk factor for arterial disease.

OBJECTIVES: The aim of this study was to assess the vitamin D status in patients with occlusive or aneurysmatic arterial disease in relation to clinical cardiovascular risk profiles and markers of atherosclerotic disease. METHODS: We included 490 patients with symptomatic peripheral arterial disease (PAD, n = 254) or aortic aneurysm (n = 236). Cardiovascular risk factors and comorbidities carotid intima-media thickness (CIMT), ankle-brachial index (ABI), serum high-sensitive C-reactive protein (hs-CRP) and vitamin D were assessed. Patients were categorised into severely (≤25 nmol l(-1)) or moderately (26-50 nmol l(-1)) vitamin D deficient, vitamin D insufficient (51-75 nmol l(-1)) or vitamin D sufficient (>75 nmol l(-1)). RESULTS: Overall, 45% of patients suffered from moderate or severe vitamin D deficiency. The prevalence of vitamin D deficiency was similar in patients with PAD and those with an aortic aneurysm. Low levels of vitamin D were associated with congestive heart failure and cerebrovascular disease. Adjusting for clinical cardiovascular risk factors, multivariable regression analyses showed that low vitamin D status was associated with higher CIMT (P = 0.001), lower ABI (P < 0.001) and higher hs-CRP (P = 0.022). CONCLUSIONS: The current study shows a strong association between low vitamin D status and arterial disease, independent of traditional cardiovascular risk factors and irrespective of the type of vascular disease, that is, occlusive or aneurysmatic disease.

A randomised study of perioperative esmolol infusion for haemodynamic stability during major vascular surgery; rationale and design of DECREASE-XIII.

OBJECTIVES: This article describes the rationale and design of the DECREASE-XIII trial, which aims to evaluate the potential of esmolol infusion, an ultra-short-acting beta-blocker, during surgery as an add-on to chronic low-dose beta-blocker therapy to maintain perioperative haemodynamic stability during major vascular surgery. DESIGN: A double-blind, placebo-controlled, randomised trial. MATERIALS & METHODS: A total of 260 vascular surgery patients will be randomised to esmolol or placebo as an add-on to standard medical care, including chronic low-dose beta-blockers. Esmolol is titrated to maintain a heart rate within a target window of 60-80 beats per minute for 24 h from the induction of anaesthesia. Heart rate and ischaemia are assessed by continuous 12-lead electrocardiographic monitoring for 72 h, starting 1 day prior to surgery. The primary outcome measure is duration of heart rate outside the target window during infusion of the study drug. Secondary outcome measures will be the efficacy parameters of occurrence of cardiac ischaemia, troponin T release, myocardial infarction and cardiac death within 30 days after surgery and safety parameters such as the occurrence of stroke and hypotension. CONCLUSIONS: This study will provide data on the efficacy of esmolol titration in chronic beta-blocker users for tight heart-rate control and reduction of ischaemia in patients undergoing vascular surgery as well as data on safety parameters.

Risk of cardiovascular disease and chronic kidney disease in diabetic patients with non-alcoholic fatty liver disease: just a coincidence?

Non-alcoholic fatty liver disease (NAFLD) is estimated to afflict ~20-30% of the general population, and over 70% of the patients with Type 2 diabetes. Given the expected rise in the prevalence of obesity and diabetes, NAFLD will be, if not already there, an epidemic. The consequences of NAFLD are numerous, and range from progression to chronic liver disease with its associated morbidity and mortality, to worsening insulin resistance and Type 2 diabetes, to being a contributor to both cardiovascular disease (CVD) and chronic kidney disease (CKD). NAFLD is, therefore, a complex problem with implications far beyond the liver. This review focuses on the rapidly expanding body of clinical evidence suggesting that NAFLD is associated with an increased prevalence and incidence of both CVD and CKD in patients with diabetes. This association appears to be independent of obesity, hypertension, and other potential confounding factors. However, given the heterogeneity and small number of observational studies, further research is urgently required to corroborate the prognostic role of NAFLD in the development and progression of CVD and CKD among patients with diabetes, and to further elucidate the complex and intertwined mechanisms that link NAFLD with these adverse outcomes.

Glomerular filtration rate, albuminuria and risk of cardiovascular and all-cause mortality in type 2 diabetic individuals.

BACKGROUND AND AIMS: To assess all-cause and cardiovascular mortality in type 2 diabetic individuals according to estimated glomerular filtration rate (eGFR) and albuminuria. METHODS AND RESULTS: We followed 2823 type 2 diabetic outpatients for a median period of 6 years for the occurrence of all-cause and cardiovascular mortality. eGFR was estimated using the abbreviated Modification of Diet in Renal Disease study equation. At baseline, an eGFR < 60 ml/min/1.73 m² and abnormal albuminuria were present in 22.5% and 26.0% of participants, respectively. During follow-up, a total of 309 patients died, 53% of deaths were secondary to cardiovascular causes. Risks of all-cause and cardiovascular mortality increased progressively with decreasing eGFR and increasing albuminuria. After adjustment for age, sex, body mass index, smoking, hypertension, diabetes duration, hemoglobin A1c, plasma lipids, medications use (hypoglycemic, anti-hypertensive, anti-platelet or lipid-lowering drugs) and albuminuria, the hazard ratios of all-cause and cardiovascular mortality per 1-SD decrease in eGFR were 1.53 (95%CI 1.2-2.0; p < 0.0001) and 1.51 (95%CI 1.05-2.2; p=0.023), respectively. A similar pattern in the risk of all-cause and cardiovascular mortality was seen for albuminuria (1.14, 1.01-1.3, p=0.028 and 1.19, 1.01-1.4, p=0.043 per 1-SD increase in albuminuria, respectively) after adjustment for eGFR and other potential confounders. CONCLUSIONS: These findings suggest that both decreasing eGFR and rising albuminuria are associated with all-cause and cardiovascular mortality in type 2 diabetic individuals, independently of traditional risk factors and diabetes-related variables.

Prognosis of vascular surgery patients using a quantitative assessment of troponin T release: is the crystal ball still clear?

BACKGROUND: Cardiac troponin T (cTnT) assays with increased sensitivity might increase the number of positive tests. Using the area under the curve (AUC) with serial sampling of cTnT an exact quantification of the myocardial damage size can be made. We compared the prognosis of vascular surgery patients with integrated cTnT-AUC values to continuous and standard 12-lead electrocardiography (ECG) changes. METHODS: 513 Patients were monitored. cTnT sampling was performed on postoperative days 1, 3, 7, 30 and/or at discharge or whenever clinically indicated. If cTnT release occurred, daily measurements of cTnT were performed, until baseline was achieved. CTnT-AUC was quantified and divided in tertiles. All-cause mortality and cardiovascular events (cardiac death and myocardial infarction) were noted during follow-up. RESULTS: 81/513 (16%) Patients had cTnT release. After adjustment for gender, cardiac risk factors, and site and type of surgery, those in the highest cTnT-AUC tertile were associated with a significantly worse cardiovascular outcome and long-term mortality (HR 20.2; 95% CI 10.2-40.0 and HR 4.0; 95% CI 2.0-7.8 respectively). Receiver operator analysis showed that the best cut-off value for cTnT-AUC was <0.01 days*ng m for predicting long-term cardiovascular events and all-cause mortality. CONCLUSION: In vascular surgery patients quantitative assessment of cTnT strongly predicts long-term outcome.

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and retinopathy in type 1 diabetic patients.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased prevalence of chronic kidney disease (CKD) and retinopathy in patients with type 2 diabetes. Information on this issue is lacking for type 1 diabetes. We evaluated whether NAFLD is associated with increased prevalence of retinopathy and CKD in type 1 diabetic patients. METHODS: All type 1 diabetic patients (n = 202) who regularly attended our diabetes clinic and did not have any clinical evidence of cirrhosis or other secondary causes of chronic liver disease were studied. Main study measures were detection of NAFLD (by patient history and liver ultrasound), diabetic retinopathy (diagnosed by ophthalmoscopy) and CKD (defined as abnormal albuminuria or estimated GFR of < or =60 ml min(-1) 1.73 m(-2)). RESULTS: The age- and sex-adjusted prevalence of diabetic retinopathy (53.2 vs 19.8%) and CKD (37.8 vs 9.9%) was markedly higher in patients with NAFLD than in those without (p < 0.0001). In multivariate logistic regression analysis, NAFLD was associated with prevalent retinopathy (adjusted OR 3.31, 95% CI 1.4-7.6, p = 0.005) or CKD (adjusted OR 3.90, 95% CI 1.5-10.1, p = 0.005). These associations were independent of age, sex, diabetes duration, HbA(1c), medication use and presence of the metabolic syndrome. CONCLUSIONS/INTERPRETATION: Our findings suggest that ultrasound-diagnosed NAFLD is associated, independently of several confounding factors, with a higher prevalence of CKD and retinopathy in type 1 diabetic individuals.

Relationship between serum gamma-glutamyltransferase and chronic kidney disease in the United States adult population. Findings from the National Health and Nutrition Examination Survey 2001-2006.

BACKGROUND AND AIMS: Elevated serum levels of gamma-glutamyltransferase (GGT) are a marker of liver injury, but may also be associated with other diseases and death. Currently, the association of serum GGT concentrations with chronic kidney disease has not been established in the U.S. general population. METHODS AND RESULTS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey 2001 through 2006 and examined the association between serum GGT concentrations and chronic kidney disease in a nationally representative sample of 13,188 adults aged 20 years or older. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease formula. The prevalence of chronic kidney disease defined as eGFR <60 ml/min/1.73 m(2) or abnormal albuminuria in those with eGFR ≥60 ml/min/1.73 m(2) was 13.9% (n = 1842). Serum GGT elevation was associated with an increased odds of chronic kidney disease (odds ratio 2.38, 95% confidence intervals 2.02-2.80, p<0.0001). After adjustment for demographics, comorbidities, daily alcohol consumption, lipid-lowering medications, viral hepatitis status and laboratory measures, the odds ratio of chronic kidney disease per log serum GGT increase was 1.79 (1.41, 2.27; p<0.0001). CONCLUSIONS: These results show a strong, independent, relationship of increased serum GGT concentrations with chronic kidney disease in the US adult population.

Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults. METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (< or =5.6%), tertile 2 (5.61-6.20%) and tertile 3 (> or =6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest). CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

Higher HDL cholesterol levels are associated with a lower incidence of chronic kidney disease in patients with type 2 diabetes.

BACKGROUND AND AIMS: Type 2 diabetes is one of the most important risk factor for the development of chronic kidney disease (CKD). Recently, it has been shown that lower high-density lipoprotein cholesterol (HDL-C) levels predicted the development of microalbuminuria in type 2 diabetic individuals. We have prospectively assessed the effects of plasma HDL-C levels on the incidence of CKD in a large cohort of type 2 diabetic patients. METHODS AND RESULTS: We followed 1987 type 2 diabetic outpatients with normal or near-normal kidney function at baseline for 5 years for the occurrence of incident CKD defined as glomerular filtration rate < or = 60 mL/min/1.73 m(2) (as estimated by the abbreviated Modified Diet and Renal Disease Study equation). Cox proportional hazards models were used to examine the independent relationship between plasma HDL-C levels and incident CKD. During a median follow-up of 5 years, 11.8% (n=234) of participants developed incident CKD. In multivariate regression analysis, higher HDL-C levels were associated with a lower risk of incident CKD (multiple-adjusted hazard ratio 0.76; 95% coefficient intervals 0.61-0.96; p=0.025) independently of age, gender, body mass index, hypertension, smoking history, diabetes duration, hemoglobin A1c, plasma triglycerides, LDL-cholesterol, presence of diabetic retinopathy, baseline albuminuria, and current use of medications (anti-hypertensive, anti-platelet, lipid-lowering and hypoglycemic drugs). CONCLUSIONS: Higher plasma levels of HDL-C are associated with a lower risk of incident CKD in a large cohort of type 2 diabetic adults independently of numerous confounding factors.

Prognosis of patients with peripheral arterial disease.

The incidence of peripheral arterial disease (PAD) is on the increase and is associated with a major health concern in current practical care. The most common disease process underlying PAD is atherosclerosis. Atherosclerosis is a complex generalized disease affecting several arterial beds, including the peripheral and coronary circulation. Especially in patients with PAD, high incidences of coronary artery disease (CAD) have been observed, which may be asymptomatic or symptomatic. The prognosis of patients with PAD is related to the presence and extent of underlying CAD. In patients with PAD undergoing major vascular surgery, cardiac complications are the major cause of perioperative morbidity and mortality and indicate a high-risk for adverse long-term cardiac outcome. In order to improve outcome for PAD patients, assessment and aggressive therapy of atherosclerotic risk factors and usage of cardio-protective medications is recommended. Unfortunately, substantial differences in risk factor management and treatment and long-term outcome have been reported between PAD and CAD patients.

Beta-blockers improve outcomes in kidney disease patients having noncardiac vascular surgery.

Beta-blockers are known to improve postoperative outcome after major vascular surgery. We studied the effects of beta-blockers in 2126 vascular surgery patients with and without kidney disease followed for 14 years. Creatinine clearance was calculated using the Cockcroft-Gault equation, and kidney function was categorized as Stage 1 for a reference group of 550 patients, Stage 2 with 808 patients, Stage 3 with 627 patients, and combined Stages 4 and 5 with 141 patients. Outcome measures were 30-day and long-term all-cause mortality with a mean follow-up of 6 years. Cox proportional hazards models were used to control cardiovascular risk factors, including propensity for beta-blocker use. In all, 129 (6%) and 1190 (56%) patients died respectively. Mortality rates were three- and two-fold higher, respectively, for patients at Stages 3-5 compared to the reference group for the two outcomes. beta-Blocker use was significantly associated with a lower risk of mortality after surgery. The overall adjusted hazard ratio was 0.35 and 0.62, respectively, for individuals at Stages 3-5 compared to the reference group for 30-day and long-term mortality. This study shows that kidney function is a predictor of all-cause mortality and beta-blocker use is associated with a lower risk of death in kidney disease patients undergoing elective vascular surgery.

25-Hydroxyvitamin D, insulin resistance, and kidney function in the Third National Health and Nutrition Examination Survey.

Previous research has reported reduced serum 25-hydroxyvitamin D levels in patients with chronic kidney disease (CKD), although the relationship between vitamin D status and insulin resistance (IR) in patients with CKD has not been examined in the general population. We examined the association that kidney function, based on glomerular filtration rate (eGFR) estimated from serum creatinine, has with serum levels of 25-hydroxyvitamin D and components of the metabolic syndrome among 14 679 participants in the Third National Health and Nutrition Examination Survey (NHANES III). In this analysis, adjusted mean serum 25-hydroxyvitamin D was significantly lower only in the participants with a severe (15-29 ml/min/1.73 m(2)) decrease in eGFR compared to those with normal kidney function (61.6 vs 73.3 nmol/l, P=0.0063). Serum 25-hydroxyvitamnin D (P=0.0018) and level of kidney function (P=0.0003) were inversely associated, independent of each other, with homeostasis model assessment of insulin resistance (HOMA-IR), adjusting for confounders. Participants with high 25-hydroxyvitamin D levels (>81 nmol/l) had lower HOMA-IR. We conclude that 25-hydroxyvitamin D deficiency is not as prevalent in the US general population with decreased eGFR as previously reported in patients with CKD; and that vitamin D and kidney function have independent inverse associations with IR.

Should we biopsy kidneys of patients post-liver transplant?

Thirty days after orthotropic liver transplantation, a 52-year-old Hispanic male developed full-blown nephrotic syndrome. Although the patient was posttransplantation, he underwent a kidney biopsy under real-time ultrasound guidance. The pathological specimen revealed membranous nephropathy. A change in the immunosuppressive regimen resulted in a rapid decrease in urinary protein excretion, leading to resolution of the nephrotic syndrome. We report this case to illustrate the precautions that need to be taken when liver transplant patients require a kidney biopsy.