The effects of ramipril in individuals at risk for Alzheimer's disease: results of a pilot clinical trial.

Research shows that certain antihypertensives taken during midlife confer Alzheimer's disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-ß (Aß) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD. This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E ε4 (APOE ε4) status and randomized to receive 5 mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Aß(1-42) and ACE activity, arterial function, and cognition. Participants were middle-aged (mean 54 y) and highly educated (mean 15.4 y), and included 50% men and 50% APOE ε4 carriers. While results did not show a treatment effect on CSF Aß(1-42) (p = 0.836), data revealed that ramipril can inhibit CSF ACE activity (p = 0.009) and improve blood pressure, however, there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved blood pressure, but did not influence CSF Aß1-42. While larger trials are needed to confirm our CSF Aß results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of angiotensin II-mediated inhibition of acetylcholine.

Web-based resources for medical nutrition education.

The World Wide Web is a valuable source of nutrition and health information, but the time and effort required to take advantage of this resource may stand in the way of routine use in medical education and practice. The Nutrition Academic Award (NAA) has produced numerous examples of Web-based nutrition resources, including nutrition assessment tools, patient education materials, and presentations and curricula for professional education. The University of Wisconsin Medical Nutrition Handbook provides evidence-based nutrition care guides for common clinical problems, including obesity, diabetes, hypertension, lipid disorders, and the metabolic syndrome. Incorporation of these resources into medical practice may increase the provision of effective nutrition care.

Office systems for heart disease prevention.

The provision of heart disease prevention services in primary care is currently inadequate, but can be improved with the establishment of a practice system. The system process involves all members of the practice in a clearly defined, well-organized approach to patient care. An initial review of patient care services will help practices identify prevention areas that they would like to improve by defining protocols, roles, and routines within the practice. Once established, the prevention system can improve patient care and satisfaction of practice staff and physicians, but requires on-going assessment, modification, and commitment.

Effects of multivitamins and low-dose folic acid supplements on flow-mediated vasodilation and plasma homocysteine levels in older adults.

BACKGROUND: Hyperhomocysteinemia is associated with aging, endothelial dysfunction, and increased risk of coronary heart disease in older adults; however, the effects of homocysteine-lowering therapy on vascular reactivity in older persons are unknown. The objective of this study was to determine the effects of multivitamins (MV) and folic acid (FA) supplements on flow-mediated vasodilation (FMD) in older adults. METHODS: Individuals > or =70 years old with homocysteine levels > or =10 micromol/L were recruited for this 40-week, prospective, single-blinded study. All subjects were treated sequentially, with each of the following daily therapies for 10 weeks: (1) placebo, (2) MV (400 microg FA, 6 mg vitamin B6, 25 microg vitamin B12), (3) placebo, then (4) MV + FA (total FA, 1400 microg). FMD, folate intake, and laboratory values were measured at each visit. Investigators were blinded to subject treatment phase when measuring vessel diameters and calculating FMD. RESULTS: Twenty subjects (mean +/- SEM age, 78.0 +/- 1.2 [range, 70 to 88] years, 9 women) completed the MV and 17 completed the MV + FA interventions. FMD was impaired at baseline (2.0% +/- 1.2%). During the 40-week study, homocysteine levels decreased by 1.4 +/- 0.9 micromol/L (p(trend) = 0.034) from a baseline of 12.8 +/- 0.6 micromol/L; however, FMD did not change significantly (p(trend) = 0.874). FMD did not improve after therapy with MV alone (3.0% +/- 0.9% [week 10] vs 2.4% +/- 1.1% [week 20], P =.716) or with MV + FA (2.6% +/- 0.9% [week 30] vs 1.9% +/- 0.7% [week 40], P =.484). CONCLUSIONS: At doses commonly prescribed in clinical practice, MV and FA supplements did not improve FMD in older adults with hyperhomocysteinemia.

Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors.

BACKGROUND: Although recommended as initial therapy for patients with dyslipidemia who are taking human immunodeficiency virus protease inhibitors (HIV PIs), the effects of pravastatin on lipoproteins and arterial reactivity have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in patients with dyslipidemia who are receiving HIV PIs. METHODS: This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 patients who were taking HIV PIs. Lipoprotein subfractions were measured with nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was evaluated with high-resolution ultrasound scanning. RESULTS: At baseline, subjects had an increased concentration of low-density lipoprotein (LDL) particles (1756 +/- 180 nmol/L), which tended to be small (19.9 +/- 0.2 nm), a low concentration of large high-density lipoproteins (HDL; 0.94 +/- 0.07 mmol/L), and an increased concentration of large very low-density lipoproteins (VLDL; 1.90 +/- 0.58 mmol/L). FMD was impaired (4.5% +/- 1.1%). Compared with placebo, pravastatin resulted in a 20.8% reduction in LDL particles (P =.030), a 26.7% reduction in small LDL (P =.100), and a 44.9% reduction in small VLDL (P =.023). Total and non-HDL cholesterol levels decreased by 18.3% (P <.001) and 21.7% (P <.001), respectively. FMD tended to increase in patients receiving pravastatin (0.7% +/- 0.6%); however, the difference between treatment phases was not statistically significant (P =.080). CONCLUSIONS: This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipids, lipoprotein subfractions, and endothelial function in patients taking HIV PIs. Pravastatin reduced concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events.

Teaching nutrition skills to primary care practitioners.

Primary care physicians have the potential to decrease morbidity and mortality for many chronic diseases if they provide effective nutrition counseling. Given the time constraints of primary care practice, nutrition counseling needs to be brief, be part of an organized office system and refer appropriate patients to qualified nutrition professionals to be effective. This paper reviews a system of primary care nutrition counseling using the 5A's of patient-centered counseling, the elements necessary to develop an office-based system and some successful tools developed by nutrition researchers for the primary care setting to be used in an office-based system.

Nonresponse bias: does it affect measurement of clinician behavior?

BACKGROUND: Previous studies of nonresponders have not assessed the effects of nonresponse on the accuracy of clinician behavior measurements. Knowledge of these effects is critical to both research and quality improvement. OBJECTIVE: To evaluate the hypothesis that nonresponders to a survey would not adversely affect the ability to measure rates of preventive services. RESEARCH DESIGN: Four primary-care medical practices participating in a randomized clinical trial provided an unusual opportunity to compare the medical record-documented care of both responders and nonresponders to a survey of their patients. SUBJECTS: Three hundred forty-five nonresponders and 321 responders to a questionnaire requesting participation in the study. MEASURES: Differences in patient characteristics and diseases and documentation of screening and management of tobacco use, hypertension, and hypercholesterolemia. RESULTS: Although the survey process resulted in a response rate of only 52.5% and some statistically significant differences in responder and nonresponder characteristics, there were no differences in management behavior regarding cardiovascular risk factors. Responders were more likely to have adjusted documentation of tobacco use (OR = 1.4), blood pressure measurement (OR = 9.8), and cholesterol testing (OR = 2.0), but not family history of cardiovascular disease. The most striking difference in subject characteristics was that 22.0% of nonresponders and only 12.1% of responders were tobacco users (P = 0.002). CONCLUSIONS: This study confirms that survey nonresponders may have some different characteristics and risk factor screening rates than responders. However, if confirmed by others, nonresponders who have risk factors identified may not be managed differently than responders.