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ABSTRACT: The long-term effects of smoking and smoking cessation on markers of cardiovascular disease (CVD) prognosis obtained during treadmill stress testing (TST) are unknown. The purpose of this study was to evaluate the long-term effects of smoking cessation and continued smoking on TST parameters that predict CVD risk.
In a prospective, double-blind, randomized, placebo-controlled trial of 5 smoking cessation pharmacotherapies, symptom-limited TST was performed to determine peak METs, rate-pressure product (RPP), heart rate (HR) increase, HR reserve, and 60-second HR recovery, before and 3 years after the target smoking cessation date. Relationships between TST parameters and treatments among successful abstainers and continuing smokers were evaluated using multivariable analyses.
At baseline, the 600 current smokers (61% women) had a mean age of 43.4 (SD 11.5) years and smoked 20.7 (8.4) cigarettes per day. Their exercise capacity was 8.7 (2.3) METs, HR reserve was 86.6 (9.6)%, HR increase was 81.1 (20.9) beats/min, and HR recovery was 22.3 (11.3) beats. Cigarettes per day and pack-years were independently and inversely associated with baseline peak METs (P < .001), RPP (P < .01, pack-years only), HR increase (P < .05), and HR reserve (P < .01). After 3 years, 168 (28%) had quit smoking. Abstainers had greater improvements than continuing smokers (all P < .001) in RPP (2,055 mm Hg beats/min), HR increase (5.9 beats/min), and HR reserve (3.7%), even after statistical adjustment (all P < .001).
Smokers with a higher smoking burden have lower exercise capacity, lower HR reserve, and a blunted exercise HR response. After 3 years, TST improvements suggestive of improved CVD prognosis were observed among successful abstainers.
American heart journal 01/2012; 163(1):81-87.e1. · 4.65 Impact Factor
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ABSTRACT: We examined the association between ambulatory activity and biological markers of health in smokers.
Baseline data from 985 subjects enrolled in a pharmacologic smoking cessation trial were examined. Body size, blood pressure, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), total and small LDL particles, LDL size, high density lipoprotein cholesterol, triglycerides (TG), C-reactive protein (CRP), creatinine, fasting glucose, and hemoglobin A1c were assessed in relation to pedometer-assessed ambulatory activity, as was the odds of metabolic syndrome and CRP > 3 mg/L. Effect modification by gender was examined.
Only waist circumference was lower with greater steps/day in the men and women combined (P(trend) < 0.001). No other significant relationships were noted in men, while women with ≥ 7500 steps/day had lower weight, BMI, CRP, TG, total, and small LDL particles compared with those with < 7500 steps/day. These women also had 62% and 43% lower odds of metabolic syndrome and elevated CRP, respectively, compared with the less active women. Adjustment for BMI attenuated all the associations seen in women.
Greater ambulatory activity is associated with lower levels of metabolic and cardiovascular risk factors in female smokers which may, in part, be mediated by a reduction in BMI.
Journal of Physical Activity and Health 09/2011; 8(7):994-1003.
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ABSTRACT: This study sought to evaluate national levels of elevated low-density lipoprotein cholesterol (LDL-C) before and after publication of the Adult Treatment Panel III (ATP III). The ATP III guidelines intensified LDL-C targets and defined additional high-risk conditions. These recommendations are expected to have a noticeable impact on US cholesterol levels.
Coronary heart disease (CHD) risk was determined per ATP III guidelines for US residents aged 20 to 79 years in the 1999 to 2000 and 2001 to 2002 surveys. For those at high risk, the LDL-C mean percentage <100 mg/dL and percentage > or =130 mg/dL, although not taking lipid-lowering therapy, were compared between the 2 surveys. In addition, subsets with and without CHD were evaluated.
Of all high-risk US residents, the mean LDL-C dropped from 129 mg/dL in 1999 to 2000 to 120 mg/dL in 2001 to 2002 (P = .003). Those <100 mg/dL increased from 23% to 32% (P = .003). Those > or =130 mg/dL and not on medication dropped from 36% to 27% (P = .001). Goal achievement and improvements were more favorable in the subset with CHD compared with those at high risk due to high-risk equivalent conditions.
The sharp increase in high-risk US residents at the goal and the drop in the untreated percentage of those above treatment threshold illustrate national improvements in the management of LDL-C for those at high coronary risk. High-risk subjects without CHD displayed less significant improvements, suggesting an opportunity for better recognition and management of these individuals.
American heart journal 08/2008; 156(2):284-91. · 4.65 Impact Factor
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Cynthia M Carlsson,
Carey E Gleason,
Timothy M Hess,
Kimberly A Moreland,
Hanna M Blazel,
Rebecca L Koscik,
Nathan T N Schreiber,
Sterling C Johnson,
Craig S Atwood,
Luigi Puglielli,
Bruce P Hermann, Patrick E McBride,
James H Stein,
Mark A Sager,
Sanjay Asthana
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ABSTRACT: Statins reduce amyloid-beta (Abeta) levels in the brain and cerebrospinal fluid (CSF) in animals and may thereby favorably alter the pathobiology of AD. It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD.
In a 4-month randomized, double-blind, controlled study, we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Abeta42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD.
Compared to placebo, individuals randomized to simvastatin for 4 months had similar changes in CSF Abeta42 (p=0.344) and total tau levels (p=0.226), yet greater improvements in some measures of verbal fluency (p=0.024) and working memory (p=0.015). APOE4 genotype, gender, and vascular risk factors were associated with CSF biomarker levels, but did not modify treatment effects.
In asymptomatic middle-aged adults at increased risk for AD, simvastatin use improved selected measures of cognitive function without significantly changing CSF Abeta42 or total tau levels. Further studies are needed to clarify the impact of higher dose and/or longer duration statin therapy on not only Abeta metabolism, but also other preclinical processes related to the development of AD.
Journal of Alzheimer's disease: JAD 04/2008; 13(2):187-97. · 3.74 Impact Factor
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ABSTRACT: Imaging techniques to identify subclinical atherosclerosis are becoming more widespread, but few data exist regarding their influence on patient or physician behavior. We evaluated the impact of ultrasound screening to identify carotid artery plaques on physician treatment plans and patient motivation.
Subjects included asymptomatic patients without known vascular disease who had 2 or more cardiac risk factors. Circumferential scanning of the right and left carotid arteries to identify carotid plaques was performed using a handheld ultrasound device in an office setting. The physician's initial treatment recommendations were assessed before and after the results of the carotid scan were reported. Subjects completed a survey to assess motivation to make lifestyle changes before and after the results of the scan were provided.
Fifty subjects were enrolled over 9 months. Their mean (SD) age was 54.0 (10.4) years and their mean Framingham 10-year cardiovascular risk was 7.8% (7.9%). More than half (58%) of the subjects had at least one carotid plaque. When carotid plaque was identified, physicians were more likely to prescribe aspirin (P = .031) and lipid-lowering therapy (P = .004). Although subjects with carotid plaque reported an increase in their perceived likelihood of developing heart disease (P = .013), they did not report increased motivation to make lifestyle changes.
Ultrasound screening for carotid plaque in an office setting can alter physician treatment plans. Although the presence of plaque increased patient perception of cardiovascular risk, it did not motivate patients to make lifestyle changes.
American heart journal 01/2008; 154(6):1072-7. · 4.65 Impact Factor
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ABSTRACT: C-reactive protein (CRP) is the most well-studied inflammatory marker for the prediction of coronary artery disease. It was hypothesized that population-wide screening would have minimal impact but that a target population might be identified for whom CRP testing could be appropriate. The National Health and Nutrition Examination Survey (NHANES; 1999 to 2002) included 7,399 subjects who represented 171 million United States residents aged 20 to 79 years. Subjects were risk stratified according to National Cholesterol Education Program Adult Treatment Panel III guidelines. Subjects with CRP levels >3 mg/L then had their risk profiles adjusted by adding 1 risk factor and multiplying their Framingham risk scores by 1.5. Subjects had their low-density lipoprotein (LDL) cholesterol goals adjusted as necessary and were then recategorized as above or below their CRP-adjusted LDL cholesterol goal. LDL cholesterol goals were met initially by 67.8% (116 +/- 8 million) of United States residents, and 64.8% (111 +/- 8 million) achieved their LDL cholesterol goals after CRP adjustment. Thus, 5.3 +/- 1.1 million of the population (3.1 +/- 0.1%) had their risk modified in a clinically meaningful way by CRP adjustment. Targeting the screening to 2 groups, those with 1 risk factor and LDL cholesterol levels 130 to 159 mg/dl and those with moderately high risk and LDL cholesterol levels 100 to 129 mg/dl, we were able to identify all 5.3 million by screening only 14.8 million, achieving a screening yield of 35%. In conclusion, population-based screening with CRP provided a clinical impact for only 3.1% of United States residents. Patients with 1 risk factor and LDL cholesterol levels of 130 to 159 mg/dl and those with moderately high risk and LDL cholesterol levels of 100 to 129 mg/dl represent high-yield subgroups for routine CRP screening.
The American Journal of Cardiology 11/2007; 100(7):1130-3. · 3.37 Impact Factor
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ABSTRACT: Updated guidelines from the National Cholesterol Education Program Adult Treatment Panel III stratify patients into 5 groups of coronary heart disease (CHD) risk that determine intensity of lipid-lowering therapy. The present study assesses the distribution of low-density lipoprotein cholesterol (LDL-C) in the United States across the 5 groups of CHD risk as defined in the updated guidelines.
Subjects included 7399 individuals 20 to 79 years of age in the 1999 to 2002 National Health and Nutrition Examination Survey representing 171 million individuals in the United States. CHD risk, LDL-C levels, and goal achievement were determined per Adult Treatment Panel III guidelines. CHD risk assessment incorporated a medical condition review, risk factor summation, and Framingham Risk Score calculation. Percentages were weighted to represent population estimates, and SEs were adjusted for the survey design. The distribution of individuals by CHD risk included 61.1% at lower risk, 10.6% at high risk, and 5.7% at very high risk. From Adult Treatment Panel III criteria, only 5.4% of the population was at "intermediate" risk. Two thirds (66.3%) met their Adult Treatment Panel III-defined LDL-C goal. Of those at high and very high risk, 23% and 26%, respectively, met the goal of LDL-C <100 mg/dL, whereas only 3.1% and 4.6% had an LDL-C <70 mg/dL (or non-high-density lipoprotein C <100 mg/dL).
Most adult US residents are at lower 10-year CHD risk and meet risk-adjusted LDL-C goals. However, large portions of the high-risk population are undertreated. The commonly described population at intermediate risk is small. A novel method of identifying patients who might benefit from additional testing to determine their treatment strategy is provided.
Circulation 03/2007; 115(11):1363-70. · 14.74 Impact Factor
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Nature Clinical Practice Cardiovascular Medicine 01/2007; 3(12):640-1. · 7.04 Impact Factor
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ABSTRACT: Ultrasound detection of carotid plaque can be performed with equipment that is available in many clinical settings and can identify patients at increased risk of cardiovascular (CV) disease. We reviewed the literature to determine the CV risk factors associated with the presence of carotid plaque and whether its presence is associated with the presence and extent of coronary artery disease. A MEDLINE search subsequently was performed to determine whether carotid plaque burden predicts future CV events. Studies that had more than 300 subjects and reported hazard ratios or relative risk estimates for CV events, or data from which these values could be calculated, were included. References from identified studies also were examined for inclusion in the review. Nine studies met these criteria. Although there was not a uniform definition of carotid plaque, eight studies found that the presence of carotid plaque predicted incident CV death and/or myocardial infarction. In several studies, this relationship persisted after adjustments for risk factors. Ultrasound detection of carotid plaque is a straightforward, inexpensive, and safe tool that has the potential to be used in an office setting to help clarify a patient's CV risk.
Vascular Medicine 06/2006; 11(2):123-30. · 1.46 Impact Factor
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ABSTRACT: 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.
American Journal of Clinical Nutrition 05/2006; 83(4):951S-955S. · 6.67 Impact Factor
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Primary Care Clinics in Office Practice 04/2006; 33(1):75-91, viii-ix. · 1.01 Impact Factor
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ABSTRACT: 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.
Primary Care Clinics in Office Practice 01/2006; 32(4):883-900. · 1.01 Impact Factor
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ABSTRACT: Dyslipidemia is common among patients receiving antiretroviral therapy for HIV infection. The purpose of this study was to determine whether postprandial lipemia contributes to the dyslipidemia observed in HIV-positive patients taking antiretroviral therapy.
A standardized fat load was administered to 65 subjects (group 1 35 HIV-positive subjects receiving protease inhibitors [PIs]; group 2 20 HIV-positive subjects not receiving PIs; group 3 10 HIV-negative controls). Serum triglycerides, retinyl palmitate, and lipoproteins were measured using enzymatic and nuclear magnetic resonance spectroscopic techniques. Compared with HIV-negative controls, peak postprandial retinyl palmitate and large very low-density lipoprotein (VLDL) levels occurred later in both HIV-positive groups, and a delayed decrease in serum triglycerides was observed. However, postprandial areas under the curve (AUCs) for triglycerides, retinyl palmitate, chylomicrons, and large VLDL were similar. Postprandial AUCs for intermediate-density lipoproteins (IDLs) and low-density lipoproteins (LDLs) were higher in group 1 than groups 2 and 3 (all P<0.035).
Postprandial clearance of triglyceride-rich lipoproteins is delayed in HIV-positive individuals receiving antiretroviral therapy. Compared with HIV-positive individuals not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial IDLs and LDLs. An oral fat load was administered to 55 HIV-positive and 10 HIV-negative individuals. Postprandial clearance of triglyceride-rich lipoproteins was delayed in HIV-positive individuals. Compared with HIV-positive subjects not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial intermediate-density and low-density lipoproteins.
Arteriosclerosis Thrombosis and Vascular Biology 03/2005; 25(2):399-405. · 6.37 Impact Factor
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Diabetes Care 02/2005; 28(1):145-7. · 8.09 Impact Factor
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ABSTRACT: Diabetic retinopathy and proteinuria, manifestations of microvascular abnormalities, occur early in the course of diabetes mellitus; in contrast, macrovascular cardiovascular complications usually occur later. Retinal vessel characteristics may be informative about risk of cardiovascular disease in persons with diabetes. We evaluated this in a longitudinal cohort study of persons with type 1 diabetes.
The population consisted of persons with type 1 diabetes who were receiving care in 11 counties in Wisconsin. Subjects (n = 996) were examined at baseline (1980-1982), and 4, 10, 14, and 20 years later. Evaluations included medical history and measurements of height, weight, blood pressure, and glycosylated hemoglobin. Fundus photographs were graded for diabetic retinopathy at baseline, and the same photographs were graded later for the diameters of retinal blood vessels. At each examination, a history of cardiovascular disease events since the last examination (and prior to baseline) was obtained. Mortality was monitored yearly.
The 20-year age-adjusted cumulative incidences were 18.1% for angina, 14.8% for myocardial infarction, and 5.9% for stroke. Severity of diabetic retinopathy was associated with angina and stroke. Arteriovenous ratio was associated with myocardial infarction. Of 273 deaths, 176 involved heart disease. The severity of retinopathy and arteriovenous ratio was associated with heart disease mortality. Nephropathy was more informative about the cardiovascular end points than were the blood vessel characteristics.
Incidences of cardiovascular disease, including mortality, were common in people with type 1 diabetes during a 20-year interval. Retinal vascular characteristics were associated with these end points, but this association was confounded by nephropathy.
Archives of Internal Medicine 10/2004; 164(17):1917-24. · 11.46 Impact Factor
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ABSTRACT: An imaging test that quantifies atherosclerotic burden and that can be integrated with existing risk stratification paradigms would be a very useful clinical tool.
Measurement of carotid intima-media thickness (CIMT) is feasible in a clinical setting. Such measurements can be integrated into coronary risk assessment models.
Carotid intima-media thickness was measured by B-mode ultrasound in 82 consecutive patients without manifest atherosclerotic vascular disease. The values were used to determine "vascular age" (VA) based on nomograms from the Atherosclerosis Risk in Communities study. Vascular age was substituted for chronological age and standard and vascular age-adjusted 10-year coronary heart disease (CHD) risk estimates were compared.
The mean chronological age was 55.8 +/- 9.0 years. The mean VA using CIMT was 65.5 +/- 18.9 years (p < 0.001). The Framingham 10-year hard CHD risk estimate was 6.5 +/- 4.9%. Substituting CIMT-derived VA for chronological age increased the 10-year CHD risk estimate to 8.0 +/- 6.8% (p < 0.001). Of 14 subjects initially at intermediate risk, 5 (35.7%) were reclassified as higher risk and 2 (14.3%) were reclassified as lower risk. Significant predictors of reclassification were tobacco use, high-density lipoprotein cholesterol, systolic blood pressure, and low-density lipoprotein cholesterol.
Measurement of CIMT, a noninvasive estimate of current atherosclerotic burden, is feasible in a clinical setting and can be integrated into CHD risk assessment models. Determining VA using CIMT values may help individualize the age component of population-based CHD risk estimates. This strategy should be tested in a large trial with hard clinical endpoints.
Clinical Cardiology 07/2004; 27(7):388-92. · 2.15 Impact Factor
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ABSTRACT: Background: An imaging test that quantifies atherosclerotic burden and that can be integrated with existing risk stratification paradigms would be avery useful clinical tool.Hypothesis: Measurement of carotid intima-media thickness (CIMT) is feasible in a clinical setting. Such measurements can be integrated into coronary risk assessment models.Methods: Carotid intima-media thickness was measured by B-mode ultrasound in 82 consecutive patients without manifest atherosclerotic vascular disease. The values were used to determine “vascular age” (VA) based on nomograms from the Atherosclerosis Risk in Communities study. Vascular age was substituted for chronological age and standard and vascular age-adjusted 10-year coronary heart disease (CHD) risk estimates were compared.Results: The mean chronological age was 55.8 ± 9.0 years. The mean VA using CIMT was 65.5 ± 18.9 years (p<0.001). The Framingham 10-year hard CHD risk estimate was 6.5 ± 4.9%. Substituting CIMT-derived VA for chronological age increased the 10-year CHD risk estimate to 8.0 ± 6.8% (p< 0.001). Of 14 subjects initially at intermediate risk, 5 (35.7%) were reclassified as higher risk and 2 (14.3%) were reclassified as lower risk. Significant predictors of reclassification were tobacco use, high-density lipoprotein cholesterol, systolic blood pressure, and low-density lipoprotein cholesterol.Conclusions: Measurement of CIMT, a noninvasive estimate of current atherosclerotic burden, is feasible in a clinical setting and can be integrated into CHD risk assessment models. Determining VA using CIMT values may help individualize the age component of population-based CHD risk estimates. This strategy should be tested in a large trial with hard clinical endpoints.
Clinical Cardiology 06/2004; 27(7):388 - 392. · 2.15 Impact Factor
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ABSTRACT: Hyperhomocysteinemia has been associated with increased risk of atherosclerosis and myocardial infarction by a number of prospective case-control studies. A variety of genetic mutations, nutritional deficiencies, disease states, and drugs can elevate homocysteine concentrations. Treatment with folic acid with or without B-complex vitamins effectively lowers homocysteine levels. Whether therapy corresponds with decreased risk of coronary events is unknown, but may be promising. This article reviews the biochemistry of homocysteine metabolism, pathogeneisis, and etiology of hyperhomocysteinemia, along with its association with coronary artery disease, screening, and treatment.
Clinical Cardiology 01/2004; 26(12):563-8. · 2.15 Impact Factor
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ABSTRACT: The prevalence of coronary artery disease (CAD) in patients with peripheral arterial disease (PAD) has been well defined. However, the prevalence of PAD in hospitalized patients with CAD has not been defined. The ankle-brachial index (ABI) is a useful non-invasive tool to screen for PAD. The aim of our study was to assess the prevalence of PAD in hospitalized patients with CAD by measuring the ABI. The study was conducted at the University of Wisconsin Hospital and Clinics inpatient Cardiovascular Medicine Service. Medically stable patients with CAD were invited to participate prior to hospital discharge. Data regarding cardiovascular risk factors, history of previous PAD, physical examination, and ABI were collected. An ABI less than or equal to 0.9 or a history of previous lower extremity vascular invention was considered to be indicative of significant PAD. A total of 100 patients (66 men and 34 women) were recruited. Forty patients were found to have PAD (mean ABI in non-revascularized patients with PAD = 0.67). By measuring the ABI, 37 (25 men) were positive for PAD and three had an ABI corrected with previous revascularization. Of these patients, 21 (52.5%) had previously documented PAD. Patients with PAD were older (p = 0.003), had a greater smoking history (p = 0.002), were more likely to have diabetes (p = 0.012), hypertension (p = 0.013) and a trend towards more dyslipidemia (p = 0.055). In conclusion, hospitalized patients with CAD are likely to have concomitant PAD. Risk factors for PAD in this patient population include advanced age, history of smoking, diabetes, hypertension, dyslipidemia and abnormal pulse examination. Identification of patients with PAD by measuring the ankle-brachial index is easily done.
Vascular Medicine 12/2003; 8(4):233-6. · 1.46 Impact Factor
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ABSTRACT: In this chapter, we have reviewed many of the steps necessary for effective CHD risk reduction. The first step in the office setting is to assess the individual CHD risk. This combines the evaluation of current CHD or a "secondary risk equivalent" with the counting of risk factors and in many cases, the absolute risk calculation. The next steps are to consider each of the major modifiable risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking status) to set goals for each and then work to achieve those goals through lifestyle changes and medication therapy. We reviewed each of these risk factors in detail and then turned to a discussion of emerging risk factors that may help "fine-tune" the risk assessment in some borderline cases. We also discussed additional non-invasive testing that is available to the clinician to help refine the assessment of current burden of disease. Finally, we discuss some of the barriers that exist on both a global and local level to effective treatment of CHD risk factors.
Primary Care Clinics in Office Practice 10/2002; 29(3):667-96. · 1.01 Impact Factor
