Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience.

BACKGROUND: Statin therapy is a proven effective treatment of hyperlipidemia. However, a significant number of patients cannot tolerate statins. This study was conducted to review treatment strategies for patients intolerant to statin therapy with a focus on intermittent statin dosing. METHODS AND RESULTS: We performed a retrospective analysis of medical records of 1,605 patients referred to the Cleveland Clinic Preventive Cardiology Section for statin intolerance between January 1995 and March 2010 with at least a 6-month follow-up. The changes in lipid profile, achievement of low-density lipoprotein cholesterol (LDL-C) goals, and statin tolerance rate were analyzed. Most (72.5%) of patients with prior statin intolerance were able to tolerate a statin for the median follow-up time of 31 months. Patients on intermittent statin dosing (n = 149) had significantly lower LDL-C reduction compared with daily dosing group (n = 1,014; 21.3% ± 4.0% vs 27.7% ± 1.4%, P < .04). However, compared with the statin discontinued group (n = 442), they had a significantly higher LDL-C reduction (21.3% ± 4.0% vs 8.3 ± 2.2%, P < .001), and a significantly higher portion achieved their Adult Treatment Panel III goal of LDL-C (61% vs 44%, P < .05). There was a trend toward a decrease in all-cause mortality at 8 years for patients on daily and intermittent statin dosing compared with those who discontinued statin (P = .08). CONCLUSIONS: Most patients with previous statin intolerance can tolerate subsequent trial of statin. A strategy of intermittent statin dosing can be an effective therapeutic option in some patients and may result in reduction in LDL-C and achievement of LDL-C goals.

Feasibility and acceptability of stepping exercise for cardiovascular fitness in women.

Nurses conducting clinical research often test the feasibility and acceptability of interventions before using them in large-scale experimental studies. This article specifically reviews stepping exercise as an intervention with women. In a literature review, three stepping modes (steptreadmill, bench/step, and stepper) were compared, with the steptreadmill being identified as the most advantageous for use in experimental research. An exemplar was constructed to illustrate feasibility and acceptability of steptreadmill exercise (motorized stair climbing) in 11 women with hypertension. Steptreadmill exercise is feasible and acceptable and shows promise for use in experimental studies where strict control over the exercise performed is required.

Readiness to exercise: a comparison of 3 instruments and an interview.

Exercise stage of change (ESOC), or readiness to exercise, has been measured using at least 13 instruments and 4 interviews, yet no comparison studies are available to determine optimal measures for use by health care providers. This pilot study compares ESOC classification between 3 instruments (scale-ladder, scale-true/false, and scale-5 choice); explores the feasibility of using a face-to-face structured interview; compares classification between instruments and interview; and examines the influence of sex, age, and education level on stage classification. Thirty healthy adults completed ESOC instruments in random order and then the interview. Scale-ladder and scale-true/false instruments exhibited almost perfect agreement (weighted kappa, 0.897). All instruments exhibited substantial agreement with interview (weighted kappa, 0.620-0.790). Stage classification did not differ significantly by sex, age, or education level. The authors recommend word clarification revision of the scale-5 choice instrument and further testing of the interview.

Antihypertensive therapy and regression of coronary artery disease: insights from the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) and Norvasc for Regression of Manifest Atherosclerotic Lesions by Intravascular Sonographic Evaluation (NORMALISE) trials.

BACKGROUND: In patients with coronary artery disease (CAD), therapies designed to prevent clinical events are not always associated with significant reduction in coronary obstruction, as measured by quantitative coronary angiography. We set out to explore the relationship between quantitative coronary angiography parameters, baseline characteristics, and clinical events in a large trial of CAD regression with antihypertensive agents. METHODS AND RESULTS: Patients randomized to amlodipine, enalapril, or placebo in the CAMELOT trial were followed for 24 months for major ischemic events. Among 431 patients participating in the angiographic and intravascular ultrasound substudy NORMALISE, 298 (99 amlodipine, 96 enalapril, and 103 placebo) had complete angiographic and intravascular ultrasound data. The patients did not differ significantly with respect to baseline characteristics (except for diabetes) or extent of CAD. After 24 months, the change in minimal lumen diameter (MLD) was -0.02 +/- 0.13 for amlodipine, -0.03 +/- 0.12 for enalapril, and -0.03 +/- 0.17 mm for placebo (P = .40). Major ischemic events occurred in 20.2%, 24%, and 25.2%, respectively (P = .68). There was no significant correlation between change in MLD and age, sex, statin therapy, or systolic blood pressure at baseline. The change in MLD did not differ in patients with and without cardiovascular events, regardless of treatment assignment (P = .54). Only the extent of CAD was independently predictive of ischemic events. CONCLUSION: As compared to placebo, amlodipine treatment resulted in fewer ischemic events after 24 months of therapy, but the clinical benefit was not associated with a commensurate improvement in arterial lumen dimensions.

Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative.

We analyzed data from the prospective Women's Health Initiative (WHI) Observational Study to examine the effects of regular use of aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer risk. We studied a population of 80,741 postmenopausal women between 50 and 79 years of age who reported no history of breast cancer or other cancers (excluding nonmelanoma skin cancer), and we completed a personal baseline interview that elicited comprehensive health information including data on breast cancer risk factors and NSAID use. All of the cases were adjudicated by WHI physicians using pathology reports. Our analysis was based on 1392 confirmed cases of breast cancer. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated with adjustment for age and other breast cancer risk factors. Regular NSAID use (two or more tablets/week) for 5-9 years produced a 21% reduction in the incidence of breast cancer (RR, 0.79; 95% CI, 0.60-1.04); regular NSAID use for 10 or more years produced a 28% reduction (RR, 0.72; CI, 0.56-0.91), and there was a statistically significant inverse linear trend of breast cancer incidence with the duration of NSAID use (P < 0.01). The estimated risk reduction for long-term use of ibuprofen (RR, 0.51; CI, 0.28-0.96) was greater than for aspirin (RR, 0.79; CI, 0.60-1.03). Subgroup analysis by breast cancer risk factors did not result in effect modification. Regular use of acetaminophen (an analgesic agent with little or no anti-inflammatory activity) or low-dose aspirin (<100 mg) was unrelated to the incidence of breast cancer. Our results indicate that the regular use of aspirin, ibuprofen, or other NSAIDs may have a significant chemopreventive effect against the development of breast cancer and underscore the need for clinical trials to confirm this effect.

Exercise accelerates wound healing among healthy older adults: a preliminary investigation.

BACKGROUND: Older adults are likely to experience delayed rates of wound healing, impaired neuroendocrine responsiveness, and increased daily stress. Exercise activity has been shown to have a positive effect on physiological functioning and psychological functioning among older adults. This study evaluated the effect of a 3-month exercise program on wound healing, neuroendocrine function, and perceived stress among healthy older adults. METHODS: Twenty-eight healthy older adults (mean age 61.0 +/- 5.5 years) were assigned randomly to an exercise activity group (n = 13) or to a nonexercise control group (n = 15). One month following baseline randomization, after exercise participants had acclimated to the exercise routine, all participants underwent an experimental wound procedure. Wounds were measured 3 times per week until healed to calculate rate of wound healing. All participants completed assessments of exercise endurance, salivary cortisol, and self-reported stress prior to randomization and at the conclusion of the intervention. RESULTS: Exercise participants achieved significant improvements in cardiorespiratory fitness, as reflected by increased oxygen consumption (VO(2)max) and exercise duration. Wound healing occurred at a significantly faster rate in the exercise group [mean = 29.2 (9.0) days] than in the nonexercise group [38.9 (7.4) days; p =.012]. Exercise participants also experienced increased cortisol secretion during stress testing following the intervention. Group differences in wound healing and neuroendocrine responsiveness were found despite low levels of self-reported stress. CONCLUSIONS: A relatively short-term exercise intervention is associated with enhanced rates of wound healing among healthy older adults. Thus, exercise activity may be an important component of health care to promote wound healing.

Diuretic resistance predicts mortality in patients with advanced heart failure.

BACKGROUND: In patients with chronic heart failure (CHF), diuretic requirements increase as the disease progresses. Because diuretic resistance can be overcome with escalating doses, the evaluation of CHF severity and prognosis may be incomplete without considering the intensity of therapy. METHODS: The prognostic importance of diuretic resistance (as evidenced by a high-dose requirement) was retrospectively evaluated in 1153 patients with advanced CHF who were enrolled in the Prospective Randomized Amlodipine Survival Evaluation (PRAISE). The relation of loop diuretic and angiotensin-converting enzyme inhibitor doses (defined by their median values) and other baseline characteristics to total and cause-specific mortality was determined by proportion hazards regression. RESULTS: High diuretic doses were independently associated with mortality, sudden death, and pump failure death (adjusted hazard ratios [HRs] 1.37 [P =.004], 1.39 [P =.042], and 1.51 [P =.034], respectively). Use of metolazone was an independent predictor of total mortality (adjusted HR = 1.37, P =.016) but not of cause-specific mortality. Low angiotensin-converting enzyme inhibitor dose was an independent predictor of pump failure death (adjusted HR = 2.21, P =.0005). Unadjusted mortality risks of congestion and its treatment were additive and comparable to those of established risk factors. CONCLUSIONS: The independent association of high diuretic doses with mortality suggests that diuretic resistance should be considered an indicator of prognosis in patients with chronic CHF. These retrospective observations do not establish harm or rule out a long-term benefit of diuretics in CHF, because selection bias may entirely explain the relation of prescribed therapy to death.

Gender differences in quality of life among cardiac patients.

OBJECTIVE: Prior studies of quality of life among cardiac patients have examined mostly men. This study evaluated gender differences in quality of life and examined the degree to which social support was associated with quality of life. METHODS: A sample of 536 patients (35% women) was recruited during a 14-month period from the inpatient cardiology service of a University-based hospital. Participants completed assessments at baseline and at 3-month intervals over the subsequent 12 months, for a total of 5 assessments. Measures at each assessment included quality of life [Mental Component Score (MCS) and Physical Component Score (PCS) from the Medical Outcomes Study--Short Form 36] and social support [Interpersonal Support Evaluation List--Short Form]. RESULTS: A total of 410 patients completed the baseline assessment and at least one follow-up, and were included in the data analyses. Linear mixed effects modeling of the MCS score revealed a significant effect of gender (p =.028) and time (p <.001), as well as a significant interaction of gender by social support (p =.009). Modeling of the PCS revealed a significant effect of gender (p =.010) and time (p <.001). CONCLUSIONS: Women with cardiac disease indicated significantly lower quality of life than men with cardiac disease over the course of a 12-month longitudinal follow-up. Social support, especially a sense of belonging or companionship, was significantly associated with emotional quality of life (MCS) among women. Strategies to increase social support may be important for health and well-being of women with cardiac disease.

Short-term effects of exercise and music on cognitive performance among participants in a cardiac rehabilitation program.

OBJECTIVE: Exercise has been associated with improved cognitive performance among patients with coronary artery disease. Music listening has been associated with enhanced cognitive functioning among healthy adults. This study evaluated the combined influence of exercise and music listening on cognitive performance among patients in cardiac rehabilitation (CR). DESIGN AND SETTING: Using a within-subjects repeated measures design, this study was conducted in an outpatient University-based CR facility. SAMPLE: Thirty-three men and women (mean age = 62.6 +/- 10.5 years) participated in this study. METHODS: Participants completed 1 exercise session accompanied by music and a second exercise session without music. Order of conditions was assigned randomly. Before and after each exercise session, participants completed a brief assessment of depression and anxiety, and a cognitive test of verbal fluency. RESULTS: The music condition was associated with significant improvements in verbal fluency, but the no-music control condition was not associated with cognitive change. CONCLUSION: The study provides preliminary evidence of the combined benefit of exercise and music listening for cognitive performance among patients in CR.

Stage-specific education/counseling intervention in women with elevated blood pressure.

Many women with elevated blood pressure who seek exercise opportunities require a flexible program with systematic follow-up. The study framework included motivational readiness (exercise stage of change) from the Transtheoretical Model and self-efficacy theory. This pilot study, which used a one-group repeated measures design, tested the feasibility of a stage-specific education/counseling intervention aimed at improving exercise outcomes in women with elevated blood pressure. Forty women completed a 2.5-hour session including prescription for moderate-vigorous exercise on their own, practice on equipment, maintenance of an exercise diary, and contracting; three follow-up calls (Weeks 1, 2, 3); a visit (Week 4); and a final call (Week 5). After the intervention, 85% of women moved to or remained in the action or maintenance stages of change, the highest levels of readiness; none relapsed. Exercise self-efficacy and benefits increased and barriers decreased (P<.05); 70% of participants increased exercise performance. The intervention was feasible. Further testing is warranted using larger samples and including a control group.

Effect of platelet antigen polymorphism on platelet inhibition by aspirin, clopidogrel, or their combination.

OBJECTIVES: We studied the modifier effect of platelet antigen polymorphism (PlA2) on platelet inhibition by acetylsalicylic acid (ASA, i.e., aspirin), clopidogrel, or their combination in patients with coronary heart disease. BACKGROUND: Clopidogrel, when administered with ASA, was shown to significantly improve the outcome of patients with acute coronary syndromes compared with patients receiving only ASA. We have shown previously that the effect of ASA on platelets is modified by the glycoprotein IIIa single nucleotide polymorphism PlA2. Hence, an important pharmacogenetic question remains whether the antiplatelet effect of clopidogrel is uniform for all patients or, like acetylsalicylic acid, more selective. METHODS: Thirty PlA1/A1 and 30 PlA1/A2 patients were assigned randomly to ASA 325 mg/day, clopidogrel 75 mg/day, or both. After 10 days, platelet function was studied. RESULTS: Clopidogrel provided stronger platelet inhibition than ASA with adenosine diphosphate as the agonist, and combination therapy resulted in greater inhibition than either inhibitor used alone (p < 0.0001). The use of ASA resulted in greater inhibition compared with clopidogrel with epinephrine (p < 0.0001) and collagen as agonists (p < 0.0001). With collagen as the agonist, platelets from PlA1/A2 donors were markedly and significantly less inhibited by ASA (p = 0.005). In contrast, with clopidogrel, no significant difference could be detected between inhibition of Pl(A1/A1) and Pl(A1/A2) platelets. CONCLUSIONS: The combination of ASA and clopidogrel appears superior to either agent alone in inhibiting platelet function. Pl(A2) functions as an important modifier for platelet responsiveness to ASA but not to clopidogrel. These findings could have significant impact on the future design of pharmacogenetic antithrombotic strategies for patients with coronary heart disease.

Psychological predictors of adherence and outcomes among patients in cardiac rehabilitation.

PURPOSE: The purpose of this study was to evaluate the effects of optimism, depression, and neuroticism on adherence and outcomes among patients in cardiac rehabilitation (CR). METHODS: Participants included 46 patients (34 men) with coronary heart disease (CHD) who completed measures of psychological functioning (optimism, depression, neuroticism), physical functioning (exercise stress test, body mass index, symptom reports), and CHD knowledge during the first week (baseline) and last week of a 12-week CR program. RESULTS: Baseline depression scores accounted for 9.5% of the variance associated with change in aerobic capacity (maximum oxygen consumption), when controlling for relevant demographic variables and program attendance. However, optimism and neuroticism were not predictive of CR outcomes. Results also indicated that program dropouts were significantly younger and reported more psychological distress at baseline than did participants who completed the program. CONCLUSION: Depression appears to have a significant influence on adherence and improvement among patients in CR, but optimism and neuroticism were not significant predictors of change.