Only 12.9% of patients attained LDL-C goal on their initial lipid-lowering drugs, and an additional 13.4% achieved goal after a change in their lipid-lowering therapy, resulting in 73.7% of patients not attaining goal after at least 3 years of follow-up, after initiation of lipid-lowering therapy. Patients who would gain the most from aggressive lipid lowering (CHD patients and patients with high baseline LDL-C) were least likely to achieve goal. More effective lipid management is needed to help these patients lower their cholesterol to goal levels or even lower.
The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the ratelimiting enzyme of cholesterol biosynthesis, 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, respectively); mucosal total and esterified cholesterol concentrations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of 125 I-labeled LDL to mucosal membranes. Feeding 2% sitosterol or 0.04% lovastatin for 1 week significantly ( P Ͻ 0.01) decreased the amounts of cholesterol absorbed per day ( Ϫ 85% and Ϫ 63%, respectively). In contrast, feeding 2% cholesterol for 1 week increased the amounts of absorbed cholesterol 27-fold, even though the percent absorption significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reductase activity ( P Ͻ 0.05) and receptor-mediated LDL binding ( P Ͻ 0.01), whereas lovastatin-and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimulation of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reductase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentrations of mucosal cholesterol, and only cholesterol-fed animals had increased mucosal esterified cholesterol concentrations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and receptor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum. -
Suicide rates among veterans are higher than those of the general US population. Although veterans compose only 7.6% of the US population, nearly 14% of American adult suicides are among veterans. The rate of suicide is 1.5 times higher among all veterans and 2.1 times higher among female veterans compared with the general population. Only 47% of all veterans are enrolled in the US Department of Veterans Affairs (VA) Healthcare System, leaving a large number either not receiving health care or receiving it outside the VA. Recent legislation has improved access to care for veterans outside the VA, highlighting the need for a broad public health approach to address veteran suicide and the need for all health care institutions and clinicians to be familiar with the unique health concerns in this population. The purpose of this narrative review was to summarize the risk factors contributing to veteran suicide and to provide guidance on how to assess and mitigate these risks. Suicide is preventable through recognition of risk and prompt intervention. Health care providers both inside and outside the VA system are uniquely situated at the intersection of the many contributing factors to veteran suicide and should have a structured, proactive approach to address the problem.
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