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1.  Use of an electronic medical record to characterize cases of intermediate statin-induced muscle toxicity 
Preventive cardiology  2009;12(2):88-94.
Statin use can be accompanied by a variety of musculoskeletal complaints. We describe the clinical characteristics of case subjects experiencing adverse statin-induced musculoskeletal symptoms within a large, population based cohort in Central Wisconsin. Case status was determined based upon elevated serum creatine kinase (CK) levels and the presence of at least one physician note reflecting an increased index of suspicion for statin intolerance. From the medical records of nearly 2 million unique patients, we identified more than 20,000 potential study subjects (∼1%) having CK data and at least one exposure to a statin drug. Manual screening was completed on 2,227 subjects with CK levels in the upper 10th percentile. Of those screened, 267 met inclusion criteria (12.0% eligibility), and 218 agreed to participate in a retrospective study characterizing the risk determinants of statin-induced muscle toxicity. Three categorical pain variables were graded retrospectively (distribution, location, and severity of pain). The presenting complaints of these case subjects were extremely heterogeneous. The number of subjects with a compelling pain syndrome (diffuse, proximal muscle pain of high intensity) increased at higher serum CK levels; the number of subjects with indeterminate pain variables decreased at higher serum CK levels. The lines reflecting these relationships cross at a CK level of approximately 1,175 U/l, approximately half the threshold level needed to make a clinical diagnosis of “myopathy” (i.e., CK > 10-fold upper limit).
PMCID: PMC3773543  PMID: 19476582
2.  Postprandial Metabolic Responses to Dietary Glycemic Index in Hypercholesterolemic Postmenopausal Women 
Preventive cardiology  2010;13(1):29-35.
Cardiovascular disease is the leading cause of death in postmenopausal women. While diet and lifestyle remain the cornerstones of prevention, a low-fat/high-carbohydrate diet is associated with hyperglycemia and hyperlipemia—atherosclerotic risk factors affected by postprandial conditions. The objective of this study was to examine the acute response of lipids and insulin to a low-fat/high-carbohydrate meal with either a high-glycemic or a low-glycemic index in healthy postmenopausal women. Fifteen healthy postmenopausal women were enrolled in a randomized crossover dietary intervention study. Levels of glucose, triglyceride, free fatty acids (FFAs), and insulin were measured preprandially and for 240 minutes after consumption of the test meals. In response to the high-glycemic compared with the low-glycemic index meal, postprandial insulin levels had a higher peak (65.4 vs 48.1 μU/mL, respectively), the homeostasis model assessment-insulin resistance (HOMA-IR) was significantly higher (P=.014), serum triglyceride levels declined significantly (P<.001), and there was a small reduction in FFA levels, although the difference did not reach statistical significance. The results suggest a postprandial impact of glycemic index on cardiovascular metabolic biomarkers in postmenopausal women and may have implications for dietary glycemic modification of cardiovascular risk in women.
PMCID: PMC3613123  PMID: 20021624
3.  Risk Factors for Subclinical Carotid Atherosclerosis among Current Smokers 
Preventive Cardiology  2010;13(4):166-171.
This study characterized the determinants of carotid atherosclerosis in a large, contemporary sample of current smokers. Associations between risk factors, carotid intima-media thickness (CIMT) and carotid plaque presence were determined by multivariable regression. Subjects included 1,504 current smokers (58% female) who were a median (interquartile range) of 44.7 (38–53) years old and smoked 25 (15–40) pack-years; 55% had plaque. Pack-years, age, male sex, non-white race, body-mass index, systolic blood pressure, small low-density lipoproteins (LDL), and total high-density lipoproteins were independently associated with CIMT (model R2=0.434, p<0.001). Pack-years (OR 1.14 per 10 pack-years, p=0.001), age (OR 1.75 per 10 years, p<0.001), body-mass index (OR 0.91 per 5 kg/m2, p =0.035), and small LDL (OR 1.11 per 100 nmol/L, p<0.001), were independently associated with carotid plaque presence (model X2=210.7, p<0.001). The association between pack-years and carotid plaque was stronger in women (OR 1.09 per 10 pack-years, pinteraction=0.018).
PMCID: PMC3276243  PMID: 20860639
atherosclerosis; carotid; arteries; lipoproteins; smoking
4.  Managing mixed dyslipidemia in special populations 
Preventive cardiology  2010;13(2):78-83.
Controlling low-density lipoprotein cholesterol is one of the major focuses of cardiovascular care. However, the twin global pandemics of obesity and diabetes are promoting an increased prevalence of associated cardiometabolic risk factors. These factors include mixed dyslipidemia, which is prevalent among several important subgroups of the overall population. Cardiovascular risk increases as women reach and extend beyond menopause, partly reflective of dyslipidemia. In addition, women with polycystic ovary syndrome display a cluster of risk factors reminiscent of the metabolic syndrome. Certain ethnic groups are also at increased risk of type 2 diabetes or the metabolic syndrome. Dyslipidemia contributes significantly to overall cardiovascular risk in the elderly, and the frequency of children and adolescents presenting with type 2 diabetes or metabolic syndrome is increasing worldwide. Physicians should be aware of the possibility of mixed dyslipidemia in patients at elevated cardiometabolic risk. However, while combination therapy may successfully correct the associated dyslipidemia, it remains to be established whether the addition of a second agent improves coronary risk beyond statin monotherapy.
PMCID: PMC2923824  PMID: 20377810
mixed dyslipidemia; HDL-cholesterol; triglycerides; metabolic syndrome; cardiometabolic risk; special populations
6.  Correlation of Normal Diastolic Cardiac Function with VO2 max in Metabolic Syndrome 
Preventive cardiology  2009;12(3):163-168.
Morbid obesity and diabetes cause diastolic dysfunction that can be detected by Doppler echocardiography. Metabolic syndrome subjects could demonstrate early diastolic dysfunction which may influence effort tolerance (VO2 max).
Methods and Results
32 subjects (17 males) who fulfilled 2 or more of the 5 metabolic syndrome criteria were studied. Average age was 37 ± 2 years. All were overweight-obese (mean BMI of 34.4 ± 0.7 kg/m2), 15 had BP > 130/85mmHg, 19 had elevated triglycerides (>150mg/dl) and 17 had low HDL cholesterol (males <40 mg/dl, females <50 mg/dl). Maximal exercise was performed using Bruce treadmill protocol with standard stress echocardiography and tissue Doppler. Maximal oxygen consumption (VO2 max) was measured using indirect calorimetry. LV filling pressure was indirectly derived from dividing pulse Doppler early mitral inflow velocity (E) by tissue Doppler early diastolic mitral annular motion (E′) or E/E′.
The group's average treadmill time was 8.06 ± 0.28 minutes, VO2 max was 28.6±1.1 ml/kg/min and 8.2 ±0.3 METs. None had evidence for myocardial ischemia, systolic or diastolic dysfunction with exercise. Mean resting E/E′ and post exercise E/E′ were 7.01 ± 0.04 and 7.41 ± 0.41 respectively. There was no significant correlation between resting E/E′ and VO2 max (r= -0.266, p=0.14). The post exercise E/E′ significantly correlated with VO2 max (r= -0.483, p=0.005) and METs (r= -0.487, p=0.005).
Diastolic function is preserved in early metabolic syndrome. Even in the normal diastolic function range, exercise E/E′ is inversely related to VO2 max. Further longitudinal studies are needed to determine if they develop diastolic dysfunction and related heart failure.
PMCID: PMC2945232  PMID: 19523060
7.  Appropriateness of Cholesterol Management in Primary Care by Sex and Level of Cardiovascular Risk 
Preventive cardiology  2009;12(2):95-101.
A study was undertaken to ascertain the appropriateness of lipid screening and management per the Third Report of the Adult Treatment Panel National Cholesterol Education Program (ATP III) guideline in a sample of North Carolina primary care practices. Demographics, cholesterol values, and comorbid conditions were abstracted from the medical records from 60 community practices participating in a randomized practice-based trial (Guideline Adherence for Heart Health). Eligible patients were aged 21 to 84 years, seen during the baseline period of June 1, 2001, through May 31, 2003, and who were not taking lipid-lowering therapy. Multivariable logistic regression was utilized to assess whether age, sex, race/ethnicity, diabetes, cardiovascular disease, ATP III risk category, or pretreatment low-density lipoprotein (LDL) influenced treatment. Among 5031 eligible patients, 1711 (34.5%) received screening lipid profiles. Screening rates were higher with older age, diabetes, and cardiovascular disease. No large differences were seen by sex. Among patients screened (mean age, 51.6 years; 57.9% female), 76.6% were appropriately managed within 4 months. In adjusted analyses, older age was associated with less appropriate treatment (odds ratio [OR] per 5 years, 0.91; P=.01), and patients with LDL cholesterol ≤130 mg/dL (OR, 18.8; P<.001) and the low-risk group (OR, 27.5; P<.001) were more likely to be managed appropriately compared with patients with LDL ≥190 mg/dL and those at high risk. Among 375 patients eligible for drug treatment, those with LDL levels between 131 and 159 mg/dL were much less likely to be treated (OR, 0.15; P<.001) compared with those with LDL >190 mg/dL, whereas risk category did not influence treatment. The challenge facing implementation of ATP III guidelines is much greater for intermediate- and high-risk patients than for low-risk patients.
PMCID: PMC2937269  PMID: 19476583
8.  Factors Associated With Low Levels of Subclinical Vascular Disease in Older Adults: Multi-Ethnic Study of Atherosclerosis 
Preventive cardiology  2009;12(2):72-79.
Coronary artery calcium (CAC), carotid intimal medial thickness (cIMT), and reduced ankle brachial indices (ABI) are markers of subclinical vascular disease strongly associated with aging. We identified factors associated with low levels of subclinical vascular disease in 1824 participants ≥70 years in the Multi-Ethnic Study of Atherosclerosis. 452 had low CAC (<25th percentile), 441 had low cIMT (<25th percentile), 1636 had normal ABI (>0.9), and 165 had a combination index indicating favorable values for all three parameters. This combination index was independently associated with younger age [OR=2.5 per 1 SD (95%CI 1.8–3.6)], female gender [OR=3.0(1.9–4.8)], lower BMI [OR=1.6 per 1 SD (1.2–2.0)], absence of hypertension [OR=1.8(1.2–2.6)], absence of dyslipidemia [OR=1.6 (1.04–2.4)], and never smoking [OR=1.7(1.1–2.6)]. No significant associations were observed for C-reactive protein, education, diet, or physical activity. Favorable levels of multiple traditional risk factors, but not several novel risk factors, were associated with subclinical markers of successful cardiovascular aging.
PMCID: PMC2932469  PMID: 19476580
9.  Control of Lipids at Baseline in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial 
Preventive cardiology  2009;12(1):9-18.
In order to examine lipids, a major treatment goal in those with diabetes and heart disease, we analyzed baseline data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial. The study consists of 2,368 participants with Type 2 diabetes and coronary artery disease from 49 sites in 6 countries (2295 provided lipid measurements). Fifty-nine percent of participants had a LDL cholesterol <100 mg/dl. Total, LDL, and non-HDL cholesterol and triglycerides differed by age group (<55, 55–64, and 65+ years), being lowest in the 65 years old. Women had higher total, LDL, and non-HDL cholesterol. Education was associated with lower total, LDL, and non-HDL cholesterol. LDL cholesterol and triglycerides were lower in the USA and Canada. Adjustment for age, gender, education, randomization year, and medication did not eliminate these differences. Geographic variation was seen which was not fully accounted for by demographic or treatment characteristics (all p values <0.05).
PMCID: PMC2717619  PMID: 19301686
10.  Walking and Non–HDL-C in Adults: A Meta-Analysis of Randomized Controlled Trials 
Preventive cardiology  2005;8(2):102-107.
An elevated level of non–high-density lipoprotein cholesterol (non–HDL-C) is a major risk factor for cardiovascular disease. The purpose of this study was to use the meta-analytic approach to examine the effects of walking on non–HDL-C in adults. Twenty-two randomized controlled trials representing 30 outcomes from 948 subjects (573 exercise, 375 control) met our inclusion criteria. Across all designs and categories, random effects modeling resulted in a significantly greater decrease in the walking group when compared with the control group of approximately 4% for non–HDL-C (X̄ ± standard error of the mean, −5.6±1.8 mg/dL, 95% confidence interval, −8.8 to −2.4 mg/dL). Meta-regression showed a statistically significant association between changes in non–HDL-C and the year of publication, with greater reductions associated with more recent publication year (R2=0.23, p=0.005). The results of this meta-analytic review suggest that walking reduces non–HDL-C in adult humans.
PMCID: PMC2447860  PMID: 15860986
11.  The Effects of Exercise on Resting Blood Pressure in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials 
Preventive cardiology  2003;6(1):8-16.
Resting blood pressure in children and adolescents can track into adulthood. The purpose of this study was to use the meta-analytic approach to examine the effects of exercise on resting systolic and diastolic blood pressure in children and adolescents. Twelve randomized, controlled trials representing 16 outcomes in 1266 subjects met the inclusion criteria. Reductions in blood pressure were approximately 1% and 3% for resting systolic and diastolic blood pressures, respectively. However, random-effects modeling using 5000 bootstrap confidence intervals revealed that neither result was statistically significant (systolic, X̄±SEM=−1±2; 95% bootstrap confidence intervals=−2 to 0 mm Hg; diastolic, X̄±SEM=−2±1; 95% bootstrap confidence intervals=−3 to 0 mm Hg). The results of this study suggest that short-term exercise does not appear to reduce resting systolic and diastolic blood pressure in children and adolescents. However, a need exists for additional studies, especially in hypertensive children and adolescents.
PMCID: PMC2447168  PMID: 12624556
12.  Exercise, Lipids, and Lipoproteins in Older Adults: A Meta-Analysis 
Preventive cardiology  2005;8(4):206-214.
The authors used the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in adults 50 years of age and older. Twenty-eight outcomes representing 1427 subjects (806 exercise, 621 control) were available for pooling. Random-effects modeling yielded statistically significant improvements of 1.1%, 5.6%, 2.5%, and 7.1%, respectively, for total cholesterol (mean ± SEM in mg/dL, −3.3±1.7; 95% confidence interval [CI], −6.5 to −0.02; p=0.05), high-density lipoprotein cholesterol (2.5±1.0; 95% CI, 0.7–4.4; p=0.01), low-density lipoprotein cholesterol (−3.9±1.9; 95% CI, −7.7 to −0.08; p=0.05), ratio of total cholesterol to high-density lipoprotein cholesterol (−0.8±0.2; 95% CI, −1.2 to −0.4; p<0.001), but not triglycerides (−7.0±3.6; 95% CI, −14.0 to 0.1; p=0.06). After conducting sensitivity analyses, only the improvements in high-density lipoprotein cholesterol and the ratio of total cholesterol to high-density lipoprotein cholesterol remained statistically significant (p<0.05 for both). It was concluded that aerobic exercise increases high-density lipoprotein cholesterol and decreases the ratio of total cholesterol to high-density lipoprotein cholesterol in older adults.
PMCID: PMC2447857  PMID: 16230875
13.  Aerobic Exercise and Resting Blood Pressure: A Meta-Analytic Review of Randomized, Controlled Trials 
Preventive cardiology  2001;4(2):73-80.
In this study the authors used the meta-analytic approach to examine the effects of aerobic exercise on resting systolic and diastolic blood pressure in adults. Forty-seven clinical trials representing a total of 72 effect sizes in 2543 subjects (1653 exercise, 890 control) met the criteria for inclusion. Statistically significant exercise-minus-control decreases were found for changes in resting systolic and diastolic blood pressure in both hypertensive (systolic, -6 mm Hg, 95% CI, -8 to -3; diastolic, -5 mm Hg, 95% CI, -7 to -3) and normotensive (systolic, -2 mm Hg, 95% CI, -3 to -1; diastolic, -1 mm Hg, 95% CI, -2 to -1) groups. The differences between groups were statistically significant (systolic, p=0.008; diastolic, p=0.000). Relative decreases were approximately 4% (systolic) and 5% (diastolic) in hypertensives, and 2% (systolic) and 1% (diastolic) in normotensives. It was concluded that aerobic exercise reduces resting systolic and diastolic blood pressure in adults.
PMCID: PMC2094526  PMID: 11828203

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