Measurements of wall shear stress and aortic pulse wave velocity in swine with familial hypercholesterolemia.

PURPOSE: To assess measurements of pulse wave velocity (PWV) and wall shear stress (WSS) in a swine model of atherosclerosis. MATERIALS AND METHODS: Nine familial hypercholesterolemic (FH) swine with angioplasty balloon catheter-induced atherosclerotic lesions to the abdominal aorta (injured group) and 10 uninjured FH swine were evaluated with a 4D phase contrast (PC) magnetic resonance imaging (MRI) acquisition, as well as with radial and Cartesian 2D PC acquisitions, on a 3T MR scanner. PWV values were computed from the 2D and 4D PC techniques, compared between the injured and uninjured swine, and validated against reference standard pressure probe-based PWV measurements. WSS values were also computed from the 4D PC MRI technique and compared between injured and uninjured groups. RESULTS: PWV values were significantly greater in the injured than in the uninjured groups with the 4D PC MRI technique (P = 0.03) and pressure probes (P = 0.02). No significant differences were found in PWV between groups using the 2D PC techniques (P = 0.75-0.83). No significant differences were found for WSS values between the injured and uninjured groups. CONCLUSION: The 4D PC MRI technique provides a promising means of evaluating PWV and WSS in a swine model of atherosclerosis, providing a potential platform for developing the technique for the early detection of atherosclerosis.

Long-term effects of smoking and smoking cessation on exercise stress testing: three-year outcomes from a randomized clinical trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A review of guidelines for dyslipidemia in children and adolescents.

The recent publication of new pediatric lipid screening guidelines represents a change in recommendations regarding lipid screening and management for pediatric patients that will affect all health care professionals who care for children and adolescents. The guidelines differ from the selective screening recommended by the 2007 US Preventive Services Task Force, instead recommending routine lipid screening for children and adolescents at ages 9-11 years and again at 17-21 years. Studies have shown that limiting lipid screening to patients with risk factors fails to identify many patients with genetic or acquired dyslipidemias. Without universal screening, many at-risk children will not be identified.

Non-high-density lipoprotein cholesterol concentration is associated with the metabolic syndrome among US youth aged 12-19 years.

OBJECTIVE: To test the hypothesis that the concentration of non-high-density lipoprotein cholesterol (non-HDL-C) is associated with the metabolic syndrome (MetS) in youth. STUDY DESIGN: Data on children and adolescents aged 12-19 years (n = 2734) from the cross-sectional National Health and Nutrition Examination Survey 1999-2004 were analyzed. RESULTS: Depending on the definition of MetS used, the mean non-HDL-C concentration among youth with MetS ranged from 144.2 to 155.8 mg/dL, compared with 108.8-109.1 mg/dL in those without MetS (all P < .001). The MetS prevalence ranged from 6.9% to 11.7% in youth with a non-HDL-C concentration of 120-144 mg/dL and from 21.5% to 23.4% in those with a concentration ≥ 145 mg/dL-both significantly higher than the prevalence of 1.9%-3.4% in youth with a concentration <120 mg/dL (all P < .001). After adjustment for potential confounders, youth with a non-HDL-C concentration ≥ 120 mg/dL or ≥ 145 mg/dL were about 3 or 4 times more likely to have MetS compared with those with a non-HDL-C <120 mg/dL or <145 mg/dL (all P < .001). CONCLUSIONS: Fasting non-HDL-C concentration was strongly associated with MetS in US youth. Our results support the use of non-HDL-C thresholds of 120 mg/dL and 145 mg/dL to indicate borderline and high MetS risk, respectively.

Increased atherogenic lipoproteins are associated with cognitive impairment: effects of statins and subclinical atherosclerosis.

Hypercholesterolemia increases the risk for dementia. Some studies suggest that statins may protect cognition, but findings are conflicting. Unmeasured confounders, including high-density lipoprotein (HDL) cholesterol or subclinical atherosclerosis, may have influenced prior study outcomes. In older adults participating in a population-based cohort study (n=1711, aged 65 to 97 y), we investigated the relationships of total and HDL cholesterol levels, statin use, and carotid intima-media thickness with the prevalence of cognitive impairment. In adjusted models, participants in the highest quartile of non-HDL (total-HDL) cholesterol had an increased odds of cognitive impairment compared with those in the lowest quartile [odds ratio (OR): 2.06, 95% confidence interval (CI): 1.07-3.98]. Statin use was associated with lower odds of cognitive impairment in unadjusted models (OR: 0.57, 95% CI: 0.36-0.89), but this relationship was not significant after adjusting for vascular and lifestyle factors (OR: 0.84, 95% CI: 0.47-1.49). In this analysis of older adults, increased atherogenic lipoproteins were associated with impaired cognition. Statin use was related to many factors that both negatively and positively affect cognition, but was not associated with better cognitive function. These results suggest that confounding by indication may explain the contradictory findings in studies assessing the association of statins with cognition. Randomized-controlled clinical trials and longitudinal studies are necessary to determine if statins protect against cognitive decline.

Connecting Rheumatology Patients to Primary Care for High Blood Pressure: Specialty Clinic Protocol Improves Follow-up and Population Blood Pressures.

OBJECTIVE: Recognizing high blood pressure (BP) as the most prevalent cardiovascular risk factor in patients with rheumatic diseases and all adults, experts recommend clinic protocols to improve BP control. The aim of this study was to adapt and implement a specialty clinic protocol, "BP Connect," to improve timely primary care follow-up after high BP measurements in rheumatology clinics. METHODS: We examined BP Connect in a 6-month preimplementation and postimplementation quasi-experimental design with 24-month follow-up in 3 academic rheumatology clinics. Medical assistants and nurses were trained to 1) check (re-measuring BPs ≥140/90 mm Hg), 2) advise (linking rheumatic and cardiovascular diseases), and 3) connect (timely [<4 weeks] primary care follow-up using protocoled electronic health record [EHR] orders). We used EHR data and multivariable logistic regression analysis to examine the primary outcome of timely primary care follow-up for patients with in-network primary care. Staff surveys were used to assess perceptions. Interrupted time series analysis was performed to examine sustainability and BP trends in the clinic populations. RESULTS: Across both 4,683 preimplementation and 689 postimplementation rheumatology visits by patients with high BP, 2,789 (57%) encounters were eligible for in-network primary care follow-up. Postimplementation, the odds of timely primary care BP measurement follow-up doubled (odds ratio 2.0, 95% confidence interval 1.4-2.9). Median time to follow-up decreased from 71 days to 38 days. Moreover, rheumatology visits by patients with high BP decreased from 17% to 8% over 24 months, suggesting significant population-level declines (P < 0.01). CONCLUSION: Implementing the BP Connect specialty clinic protocol in rheumatology clinics improved timely follow-up and demonstrated reduced population-level rates of high BP. These findings highlight a timely strategy to improve BP follow-up amid new guidelines and quality measures.

Rationale and study design of the MyHEART study: A young adult hypertension self-management randomized controlled trial.

Young adults (18-39 year-olds) with hypertension have a higher lifetime risk for cardiovascular disease. However, less than 50% of young adults achieve hypertension control in the United States. Hypertension self-management programs are recommended to improve control, but have been targeted to middle-aged and older populations. Young adults need hypertension self-management programs (i.e., home blood pressure monitoring and lifestyle modifications) tailored to their unique needs to lower blood pressure and reduce the risks and medication burden they may face over a lifetime. To address the unmet need in hypertensive care for young adults, we developed MyHEART (My Hypertension Education And Reaching Target), a multi-component, theoretically-based intervention designed to achieve self-management among young adults with uncontrolled hypertension. MyHEART is a patient-centered program, based upon the Self-Determination Theory, that uses evidence-based health behavior approaches to lower blood pressure. Therefore, the objective of this study is to evaluate MyHEART's impact on changes in systolic and diastolic blood pressure compared to usual care after 6 and 12 months in 310 geographically and racially/ethnically diverse young adults with uncontrolled hypertension. Secondary outcomes include MyHEART's impact on behavioral outcomes at 6 and 12 months, compared to usual clinical care (increased physical activity, decreased sodium intake) and to examine whether MyHEART's effects on self-management behavior are mediated through variables of perceived competence, autonomy, motivation, and activation (mediation outcomes). MyHEART is one of the first multicenter, randomized controlled hypertension trials tailored to young adults with primary care. The design and methodology will maximize the generalizability of this study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03158051.

Implications of cardiac risk and low-density lipoprotein cholesterol distributions in the United States for the diagnosis and treatment of dyslipidemia: data from National Health and Nutrition Examination Survey 1999 to 2002.

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.

National improvements in low-density lipoprotein cholesterol management of individuals at high coronary risk: National Health and Nutrition Examination Survey, 1999 to 2002.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Does detection of carotid plaque affect physician behavior or motivate patients?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Rationale for targeted rather than population based screening with C-reactive protein using the National Health and Nutrition Examination Survey (1999 to 2002).

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.

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.