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Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy.

ABSTRACT: UNLABELLED:Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100?mg or spironolactone 25?mg once daily added onto lisinopril 80?mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ?UACR differed among treatment arms (placebo -24.6%, los -38.2%, spiro -51.6%, p=0.02). No correlation existed between ?UACR and ?TG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (-20.9% vs +34.3%, p<0.01), V+I C(-18.8% vs +21.3%, p<0.01), and V+I-ApoB (-13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. TRIAL REGISTRATION NUMBER:NCT00381134; Results.

SUBMITTER: Srivastava A

PROVIDER: S-EPMC4975815 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy.

Srivastava Anand A Adams-Huet Beverley B Vega Gloria L GL Toto Robert D RD

Journal of investigative medicine : the official publication of the American Federation for Clinical Research 20160707 6

<h4>Unlabelled</h4>Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid le ...[more]

PMID: 27388615

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Project description:Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ?150 mg/dL [?1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ?500 mg/dL [?5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant's effect on TG levels correlating with the magnitude of the variant's effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the available epidemiological, clinical, and genetic evidence relating to the atherogenicity of TRLs and their role in the progression of CVD.

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Dataset Information

Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy.

Publications

Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy.

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