Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families, we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds. Soluble plasma TNFR1 levels in patients were approximately half normal. Leukocytes bearing a C52F mutation showed increased membrane TNFR1 and reduced receptor cleavage following stimulation. We propose that the autoinflammatory phenotype results from impaired downregulation of membrane TNFR1 and diminished shedding of potentially antagonistic soluble receptor. TNFR1-associated periodic syndromes (TRAPS) establish an important class of mutations in TNF receptors. Detailed analysis of one such mutation suggests impaired cytokine receptor clearance as a novel mechanism of disease.

Abstract-Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk.The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Urinary albumin/creatinine ratio (UACR) was measured at baseline and annually. Time-varying albuminuria was closely related to risk for the primary composite end point (ie, when UACR decreased during treatment, risk was reduced accordingly). When the population was divided according to median baseline value (1.21 mg/mmol) and median year 1 UACR (0.67 mg/mmol), risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 (5.5%), to low baseline/high year 1 (8.6%), to high baseline/low year 1 (9.4%), and to high baseline/high year 1 (13.5%) values. Similar significant, stepwise increases in risk were seen for the components of the primary composite end point (cardiovascular mortality, stroke, and myocardial infarction). The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure. We propose that monitoring of albuminuria should be an integrated part of the management of hypertension. If albuminuria is not decreased by the patient's current antihypertensive and other treatment, further intervention directed toward blood pressure control and other modifiable risks should be considered. Key Words: albuminuria Ⅲ angiotensin antagonist Ⅲ blood pressure Ⅲ cardiovascular diseases A ssessment of small amounts of urinary albumin excretion, so-called microalbuminuria, has become an integrated marker of cardiovascular risk in diabetic as well as nondiabetic populations. [1][2][3][4] We published data recently from a large group of patients with essential hypertension and ECG-verified left ventricular hypertrophy (LVH) from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showing a 4-to 5-fold increase in risk for cardiovascular events from the lowest to the highest decile of baseline urinary albumin excretion rate. 3 In another publication from the same hypertensive population, we showed that high urinary albumin excretion rate was related to LVH and was independent of age, blood pressure, diabetes, race, serum creatinine, or smoking. 5 This suggested cardiac organ damage was paralleling increased renal albumin excretion rate, which itself was most likely a marker of generalized hypertensionrelated damage to the peripheral vasculature. 6,7 Although baseline level of urinary albumin excretion is a powerful risk predictor, there are no data from a comprehensive study population to clarify whether a reduction in albuminuria during antihypertensive treatment relates to a ...

Background: Low-fat diets increase plasma triacylglycerol and decrease HDL-cholesterol concentrations, thereby potentially adversely affecting cardiovascular disease (CVD) risk. High-monounsaturated fatty acid (MUFA), cholesterol-lowering diets do not raise triacylglycerol or lower HDL cholesterol, but little is known about how peanut products, a rich source of MUFAs, affect CVD risk.Objective: The present study compared the CVD risk profile of an Average American diet (AAD) with those of 4 cholesterol-lowering diets: an American Heart Association/National Cholesterol Education ProgramStep II diet and 3 high-MUFA diets [olive oil (OO), peanut oil (PO), and peanuts and peanut butter (PPB)]. Design: A randomized, double-blind, 5-period crossover study design (n = 22) was used to examine the effects of the diets on serum lipids and lipoproteins: AAD [34% fat; 16% saturated fatty acids (SFAs), 11% MUFAs], Step II (25% fat; 7% SFAs, 12% MUFAs), OO (34% fat; 7% SFAs, 21% MUFAs), PO (34% fat; 7% SFAs, 17% MUFAs), and PPB (36% fat; 8% SFAs, 18% MUFAs). Results:The high-MUFA diets lowered total cholesterol by 10% and LDL cholesterol by 14%. This response was comparable with that observed for the Step II diet. Triacylglycerol concentrations were 13% lower in subjects consuming the high-MUFA diets and were 11% higher with the Step II diet than with the AAD. The high-MUFA diets did not lower HDL cholesterol whereas the Step II diet lowered it by 4% compared with the AAD. The OO, PO, and PPB diets decreased CVD risk by an estimated 25%, 16%, and 21%, respectively, whereas the Step II diet lowered CVD risk by 12%. Conclusion: A high-MUFA, cholesterol-lowering diet may be preferable to a low-fat diet because of more favorable effects on the CVD risk profile.Am J Clin Nutr 1999;70:1009-15. KEY WORDSPlasma triacylglycerol, HDL cholesterol, LDL cholesterol, monounsaturated fatty acids, dietary fat, peanuts, peanut products, Step II diet, cardiovascular disease, humans INTRODUCTIONDiet is the cornerstone of the prevention and treatment of cardiovascular disease (CVD). Currently, National Cholesterol Education Program/American Heart Association Step I or Step II diets are typically recommended for lowering blood cholesterol concentrations. The primary objective of these diets is to lower saturated fat (8-10% and < 7% of energy, respectively), cholesterol (300 or 200 mg/d), and total fat (< 30% of energy). Typically, a Step I diet lowers total cholesterol and LDL cholesterol by Ϸ5-7% (1-3). A Step II diet can lower total cholesterol and LDL cholesterol an additional 3-7% (1, 2). In these diets, saturated fat energy is replaced by carbohydrate, resulting in a low-fat, high-carbohydrate diet. Although these diets have beneficial effects on total cholesterol and LDL cholesterol, they increase plasma triacylglycerol concentrations and decrease HDL-cholesterol concentrations, thereby potentially adversely affecting CVD risk. This has caused some to question whether a Step I or Step II diet is the ideal diet for maximally reducing...

Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility, increasing serum total antioxidant capacity and HDL-cholesterol concentrations, and not adversely affecting prostaglandins.