The effect of high-dose atorvastatin on neural activity and cognitive function.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks. METHODS: Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions. RESULTS: There were few changes in standard neuropsychological tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color-Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P<.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.

A randomized controlled trial of acupuncture in stable ischemic heart disease patients.

BACKGROUND: Heart rate variability (HRV) is reduced in stable ischemic heart disease (SIHD) patients and is associated with sudden cardiac death (SCD). We evaluated the impact of traditional acupuncture (TA) on cardiac autonomic function measured by HRV in SIHD patients. METHODS: We conducted a randomized controlled study of TA, sham acupuncture (SA), and waiting control (WC) in 151 SIHD subjects. The TA group received needle insertion at acupuncture sites, the SA group received a sham at non-acupuncture sites, while the WC group received nothing. The TA and SA groups received 3 treatments/week for 12 weeks. 24-Hour, mental arithmetic stress, and cold pressor (COP) HRV was collected at entry and exit, along with BP, lipids, insulin resistance, hs-CRP, salivary cortisol, peripheral endothelial function by tonometry (PAT), and psychosocial variables. RESULTS: Mean age was 63 ± 10; 50% had prior myocardial infarction. Comparison of WC and SA groups demonstrated differences consistent with the unblinded WC status; therefore by design, the control groups were not merged. Exit mental stress HRV was higher in TA vs. SA for markers of parasympathetic tone (p ≤ 0.025), including a 17% higher vagal activity (p=0.008). There were no differences in exit 24-hour or COP HRV, BP, lipids, insulin resistance, hs-CRP, salivary cortisol, PAT, or psychosocial variables. CONCLUSIONS: TA results in intermediate effects on autonomic function in SIHD patients. TA effect on HRV may be clinically relevant and should be explored further. These data document feasibility and provide sample size estimation for a clinical trial of TA in SIHD patients for the prevention of SCD. CONDENSED ABSTRACT: We conducted a randomized, single-blind trial of traditional acupuncture (TA) vs. sham acupuncture (SA) vs waiting control (WC) in stable ischemic heart disease (SIHD) patients to evaluate cardiac autonomic function measured by heart rate variability (HRV). Exit mental stress HRV was higher in the TA compared to SA group for time and frequency domain markers of parasympathetic tone (all p ≤ 0.025), including a 17% higher vagal activity (p=0.008). These data document feasibility and provide sample size estimation for an outcome-based clinical trial of TA in SIHD patients for the prevention of sudden cardiac death.

A randomized trial of coenzyme Q10 in patients with statin myopathy: rationale and study design.

BACKGROUND: Statins are the most commonly prescribed and effective medications for reducing low-density lipoprotein levels. Some patients experience myopathic symptoms during statin treatment. The etiology is not known, but depletion of mevalonate pathway metabolites, including coenzyme Q10 (CoQ10), has been suggested. Despite a lack of conclusive evidence supporting its utility, CoQ10 supplementation has been recommended to patients who experience myalgic symptoms. OBJECTIVE: The Co-Enzyme Q10 in Statin Myopathy study is designed to examine the effect of CoQ10 supplementation on the extent and intensity of muscle pain during treatment with simvastatin. METHODS: We will recruit patients with a documented history of myalgia during statin treatment. The presence of statin-related myalgia will be confirmed in a crossover run-in trial during which the presence and absence of symptoms will be documented during statin and placebo treatment, respectively. Individuals experience myalgic symptoms while taking statins but not placebo will be randomized to receive simvastatin 20 mg daily plus either 600 mg daily of CoQ10 or placebo. Muscle pain intensity will be documented during weekly phone calls via use of the Brief Pain Inventory, Short Form. Treatment will continue for 8 weeks or until muscle symptoms are reported continuously for 1 week or become intolerable, and then subjects will crossover to the alternative treatment (CoQ10 or placebo). RESULTS: This study is an ongoing clinical trial. CONCLUSIONS: This study will determine the utility of CoQ10 for reducing pain intensity in myalgic patients and will provide guidance for clinicians treating patients with hypercholesterolemia who are intolerant to statins.

Automated quantitation of pericardiac fat from noncontrast CT.

INTRODUCTION: Increased abdominal visceral fat has been shown to be a cardiovascular risk factor. Preliminary studies indicate that pericardiac fat (PF) may provide similar information. We aimed to develop new software (QFAT) for automatic quantitation of PF from noncontrast cardiac CT and compare PF measures to other cardiovascular risk factors. METHODS: QFAT accepts user-defined range of noncontrast transverse cardiac CT slices, automatically segments the heart, and determines PF volume (PFV) as contiguous pericardial fat voxels. PFV normalized to cardiac volume defines PF ratio (PFR). QFAT and manual processing (MAN) was performed in 105 patients (mean BMI, 27; range, 17-41) by 2 observers. RESULTS: Mean processing time was 20 +/- 4 seconds for QFAT, and 9 +/- 6 minutes for MAN. There was excellent agreement between QFAT and MAN for PFV (R = 0.98) and PFR (R = 0.98). MAN and QFAT interobserver variability were comparable. Interscan and interscanner variability for PFV and PFR were comparable to corresponding interobserver variability. PFV (R = 0.88, P < 0.0001) and PFR (R = 0.81, P < 0.0001) correlated strongly with abdominal visceral fat area, moderately with BMI (R = 0.58, P < 0.0001 and R = 0.48, P < 0.0001), and weakly with abdominal subcutaneous fat area (R = 0.33, P < 0.0001 and R = 0.32, P = 0.001). CONCLUSIONS: PFV and PFR can be accurately and automatically quantified from noncontrast CT acquired for coronary calcium screening and may provide complementary information regarding cardiovascular risk.

Effects of a randomized controlled trial of transcendental meditation on components of the metabolic syndrome in subjects with coronary heart disease.

BACKGROUND: The metabolic syndrome is thought to be a contributor to coronary heart disease (CHD), and components of the syndrome have been identified as possible therapeutic targets. Previous data implicate neurohumoral activation related to psychosocial stress as a contributor to the metabolic syndrome. The aim of this study was to evaluate the efficacy of transcendental meditation (TM) on components of the metabolic syndrome and CHD. METHODS: We conducted a randomized, placebo-controlled clinical trial of 16 weeks of TM or active control treatment (health education), matched for frequency and time, at an academic medical center in a total of 103 subjects with stable CHD. Main outcome measures included blood pressure, lipoprotein profile, and insulin resistance determined by homeostasis model assessment (calculated as follows: [(fasting plasma glucose level [in milligrams per deciliter] x fasting plasma insulin level [in microunits per milliliter]) x 0.0552]/22.5); endothelial function measured by brachial artery reactivity testing; and cardiac autonomic system activity measured by heart rate variability. RESULTS: The TM group had beneficial changes (measured as mean +/- SD) in adjusted systolic blood pressure (-3.4 +/- 2.0 vs 2.8 +/- 2.1 mm Hg; P = .04), insulin resistance (-0.75 +/- 2.04 vs 0.52 +/- 2.84; P = .01), and heart rate variability (0.10 +/- 0.17 vs -0.50 +/- 0.17 high-frequency power; P = .07) compared with the health education group, respectively. There was no effect of brachial artery reactivity testing. CONCLUSIONS: Use of TM for 16 weeks in CHD patients improved blood pressure and insulin resistance components of the metabolic syndrome as well as cardiac autonomic nervous system tone compared with a control group receiving health education. These results suggest that TM may modulate the physiological response to stress and improve CHD risk factors, which may be a novel therapeutic target for the treatment of CHD.