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Faith S Luyster,1 Reginald E Dunn,2 Diane S Lauderdale,3 Mercedes R Carnethon,4 Andrew M Tucker,5 Robert A Vogel,6 Andrew E Lincoln,2 Kristen L Knutson,7 Elliot J Pellman,8–10 Patrick J Strollo Jr11 1School of Nursing, University of Pittsburgh, Pittsburgh, PA, 2Sports Medicine Research Center, MedStar Health Research Institute, Baltimore, MD, 3Department of Public Health Sciences, University of Chicago, 4Department of Preventive Medicine, Northwestern University, Chicago, IL, 5MedStar Sports Medicine, MedStar Union Memorial Hospital, Baltimore, MD, 6Cardiology Section, Department of Veterans Affairs Medical Center, Denver, CO, 7Department of Medicine, University of Chicago, Chicago, IL, 8ProHealth Care Associates, Lake Success, 9Department of Medicine, 10Department of Orthopedics, Mount Sinai School of Medicine, New York, NY, 11Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Purpose: Limited data from former National Football League (NFL) players suggest that obstructive sleep apnea (OSA) may be highly prevalent after retirement. It remains unclear whether the high prevalence of OSA in retired players is comparable to nonathletes. This retrospective analysis compared sleep apnea (SA) risk in retired NFL players to a community cohort (CARDIA Sleep study), and examined associations between SA risk and cardiovascular risk factors, including subclinical atherosclerosis.Materials and methods: Retired NFL players (n=122) were matched to CARDIA Sleep participants by age ±2 years (range 37–55 years), body mass index ±2 kg/m2, race, and male sex. Participants underwent electron-beam computed tomography to measure coronary artery calcium (CAC) and completed the Berlin Questionnaire to determine SA risk. The presence of CAC was defined as an Agatston score >0.Results: Retired NFL players had a greater prevalence of high SA risk than the matched CARDIA Sleep participants (27% vs 11.5%, P=0.002). Compared to the CARDIA Sleep participants, retired players were less likely to smoke, and had higher blood pressure, lower fasting glucose levels, and higher cholesterol levels. However, there was no difference in the prevalence of detectable CAC (30% vs 30%, P=1). In both players and the community cohort, SA risk was not significantly associated with CAC after controlling for age, race, and body mass index.Conclusion: Retired NFL players have a greater prevalence of high SA risk but similar prevalence of CAC compared with a well-matched community cohort.Keywords: sleep apnea, cardiovascular risk, coronary artery calcium, national football league

This explorative study focuses on grammatical taboos in German, morphosyntactic constructions which are subject to stigmatisation, as they regularly occur in standard languages. They are subjected to systematic experimental testing in a questionnaire study with gradient rating scales on two salient and two non-salient grammatical taboo phenomena of German. The study is divided into three subexperiments with different judgement types, an aesthetic judgement, a norm-oriented judgement and the sort of possibility judgement that comes closest to linguists’ understanding of grammar. Included in the investigated material are also examples of ordinary gradient grammaticality: unmarked, marked and ungrammatical sentences. The empirical characteristics of grammatical taboos are compared to those ordinary cases with the finding that they are rated at the level of markedness, but differ from ordinary markedness in that they produce a different pattern of between-subject variance. In addition, we find that grammatical taboos have a particular disadvantage under the aesthetic judgement type. The paper also introduces the concept of empirical grammaticality as a necessary theoretical cornerstone for empirical linguistics. Methodically, the study applies a mix of parametric and non-parametric methods of statistical analysis.

Abstract Background Leg length inequality (LLI) was identified as a problem of total hip arthroplasty soon after its introduction. Leg lengthening is the most common form of LLI. Possible consequences are limping, neuronal dysfunction and aseptic component loosening. LLI can result in an increased strain both on the contralateral hip joint and on the abductor muscles. We assessed the influence of leg lengthening and shortening on walking capacity, hip pain, limping and patient satisfaction at 2-year follow-up. Methods 478 cases with postoperative lengthening and 275 with shortening were identified, and matched with three controls each. Rigorous adjustment for potential differences in baseline patient characteristics was performed by propensity-score matching of covariates. The arbitrarily defined desired outcomes were a walking capacity >60 minutes, no hip pain, no limping, and excellent patient satisfaction. Differences in not achieving the desired outcomes between the groups were expressed as odds ratios. Results In the lengthened case group, the odds ratio for not being able to walk for an hour was 1.70 (95% CI 1.28-2.26) for cases compared to controls, and the odds ratio for having hip pain at follow-up was 1.13 (95% CI 0.78-1.64). The odds ratio for limping was 2.08 (95% CI 1.55-2.80). The odds ratio for not achieving excellent patient satisfaction was 1.67 (95% CI 1.23-2.28). In the shortening case group, the odds ratio for not being able to walk for an hour was 1.23 (95% CI 0.84-1.81), and the odds ratio for having hip pain at follow-up was 1.60 (95% CI 1.05-2.44). The odds ratio for limping for cases was 2.61 (95% CI 1.78-3.21). The odds ratio for not achieving excellent patient satisfaction was 2.15 (95% CI 1.44-3.21). Conclusions Walking capacity, limping and patient satisfaction were all significantly associated with leg lengthening, whereas pain alleviation was not. In contrast, hip pain, limping and patient satisfaction were all significantly associated with leg shortening, whereas walking capacity was not.

Abstract Immunohistochemical (IHC) assays performed on formalin-fixed paraffin-embedded (FFPE) tissue sections traditionally have been semi-quantified by pathologist visual scoring of staining. IHC is useful for validating biomarkers discovered through genomics methods as large clinical repositories of FFPE specimens support the construction of tissue microarrays (TMAs) for high throughput studies. Due to the ubiquitous availability of IHC techniques in clinical laboratories, validated IHC biomarkers may be translated readily into clinical use. However, the method of pathologist semi-quantification is costly, inherently subjective, and produces ordinal rather than continuous variable data. Computer-aided analysis of digitized whole slide images may overcome these limitations. Using TMAs representing 215 ovarian serous carcinoma specimens stained for S100A1, we assessed the degree to which data obtained using computer-aided methods correlated with data obtained by pathologist visual scoring. To evaluate computer-aided image classification, IHC staining within pathologist annotated and software-classified areas of carcinoma were compared for each case. Two metrics for IHC staining were used: the percentage of carcinoma with S100A1 staining (%Pos), and the product of the staining intensity (optical density [OD] of staining) multiplied by the percentage of carcinoma with S100A1 staining (OD*%Pos). A comparison of the IHC staining data obtained from manual annotations and software-derived annotations showed strong agreement, indicating that software efficiently classifies carcinomatous areas within IHC slide images. Comparisons of IHC intensity data derived using pixel analysis software versus pathologist visual scoring demonstrated high Spearman correlations of 0.88 for %Pos (p Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1649068103671302

Abstract Background New biomarkers that replace or are used in conjunction with the current ovarian cancer diagnostic antigen, CA125, are needed for detection of ovarian cancer in the presurgical setting, as well as for detection of disease recurrence. We previously demonstrated the upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) in the sera of ovarian cancer patients compared to healthy women using quantitative mass spectrometry. Methods LRG1 was quantified by ELISA in serum from two relatively large cohorts of women with ovarian cancer and benign gynecological disease. The expression of LRG1 in ovarian cancer tissues and cell lines was examined by gene microarray, reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, immunocytochemistry and mass spectrometry. Results Mean serum LRG1 was higher in 58 ovarian cancer patients than in 56 healthy women (89.33 ± 77.90 vs. 42.99 ± 9.88 ug/ml; p = 0.0008) and was highest among stage III/IV patients. In a separate set of 193 pre-surgical samples, LRG1 was higher in patients with serous or clear cell ovarian cancer (145.82 ± 65.99 ug/ml) compared to patients with benign gynecological diseases (82.53 ± 76.67 ug/ml, p < 0.0001). CA125 and LRG1 levels were moderately correlated (r = 0.47, p < 0.0001). LRG1 mRNA levels were higher in ovarian cancer tissues and cell lines compared to their normal counterparts when analyzed by gene microarray and RT-PCR. LRG1 protein was detected in ovarian cancer tissue samples and cell lines by immunocytochemistry and Western blotting. Multiple iosforms of LRG1 were observed by Western blot and were shown to represent different glycosylation states by digestion with glycosidase. LRG1 protein was also detected in the conditioned media of ovarian cancer cell culture by ELISA, Western blotting, and mass spectrometry. Conclusions Serum LRG1 was significantly elevated in women with ovarian cancer compared to healthy women and women with benign gynecological disease, and was only moderately correlated with CA125. Ovarian cancer cells secrete LRG1 and may contribute directly to the elevated levels of LRG1 observed in the serum of ovarian cancer patients. Future studies will determine whether LRG1 may serve as a biomarker for presurgical diagnosis, disease recurrence, and/or as a target for therapy.

Objectives: Our objective was to determine if long-term daily administration of phytonutrient supplements can prevent the immediate adverse impact of a high-fat meal and increase the production of nitric oxide.Background: Ingestion of a high-fat meal impairs flow-mediated vasodilation of the brachial artery for at least 4 h; however, co-ingestion of vitamin antioxidants or a green salad has been shown to prevent this effect.Methods: Flow-mediated brachial artery reactivity test (BART) both before and 3 h after a 900 calorie 50 g fat meal was evaluated in 38 healthy volunteers (age 36.4 +/- 10.1 years). Subjects were randomized to four weeks of daily supplementation with a powdered fruit vegetable juice concentrate (Juice Plus [JP]) along with a complex supplement providing nutritional antioxidants and various herbal extracts (Vineyard [V]), JP alone, or a matching placebo. At three and four weeks, BART was repeated both before and after the high-fat meal. Serum nitrate/nitrite concentrations were measured at baseline and at four weeks.Results: Four weeks of the JP-V combination blunted the detrimental effect of the high-fat meal (-47.5 +/- 23.4% at baseline vs. -1.7 +/- 9.7% at four weeks [p < 0.05]). Four weeks of JP alone had a similar beneficial effect (-45.1 +/- 19.7% at baseline vs. -16.6 +/- 10.3% at four weeks [p < 0.05]), whereas there was no substantial effect of the placebo. In the subjects treated with supplements, concentrations of serum nitrate/nitrite increased from 78 +/- 39 to 114 +/- 62 microm/l (p < 0.02).Conclusions: Daily ingestion of modest amounts of a fruit/vegetable juice concentrate with or without adjunctive phytonutrient supplementation can reduce the immediate adverse impact of high-fat meals on flow-mediated vasoactivity and increase nitrate/nitrite blood concentration. [ABSTRACT FROM AUTHOR]

Background: Long-term administration of beta-adrenergic blockers to patients after myocardial infarction improves survival. However, physicians are reluctant to administer beta-blockers to many patients, such as older patients and those with chronic pulmonary disease, left ventricular dysfunction, or non-Q-wave myocardial infarction.Methods: The medical records of 201,752 patients with myocardial infarction were abstracted by the Cooperative Cardiovascular Project, which was sponsored by the Health Care Financing Administration. Using a Cox proportional-hazards model that accounted for multiple factors that might influence survival, we compared mortality among patients treated with beta-blockers with mortality among untreated patients during the two years after myocardial infarction.Results: A total of 34 percent of the patients received beta-blockers. The percentage was lower among the very elderly, blacks, and patients with the lowest ejection fractions, heart failure, chronic obstructive pulmonary disease, elevated serum creatinine concentrations, or type 1 diabetes mellitus. Nevertheless, mortality was lower in every subgroup of patients treated with beta-blockade than in untreated patients. In patients with myocardial infarction and no other complications, treatment with beta-blockers was associated with a 40 percent reduction in mortality. Mortality was also reduced by 40 percent in patients with non-Q-wave infarction and those with chronic obstructive pulmonary disease. Blacks, patients 80 years old or older, and those with a left ventricular ejection fraction below 20 percent, serum creatinine concentration greater than 1.4 mg per deciliter (124 micromol per liter), or diabetes mellitus had a lower percentage reduction in mortality. Given, however, the higher mortality rates in these subgroups, the absolute reduction in mortality was similar to or greater than that among patients with no specific risk factors.Conclusions: After myocardial infarction, patients with conditions that are often considered contraindications to beta-blockade (such as heart failure, pulmonary disease, and older age) and those with nontransmural infarction benefit from beta-blocker therapy. [ABSTRACT FROM AUTHOR]

Purpose: Previous research identified decreased overall and cardiovascular mortality for National Football League (NFL) players from the 1959-1988 era. The present study explored the mortality risk among recent NFL players who played in an era of heavier linemen and nearly year-round physical conditioning., Methods: This cohort study included 9778 former NFL players with at least 1 yr in the NFL whose last season was between 1986 and 2012. Players' pension fund records were matched to the National Death Index to determine vital status, date of death, and cause of death. Standardized mortality ratios (SMR) compared player mortality through 2014 with US men of the same age, race, and calendar year. Cox proportional hazards models assessed the effect of player characteristics on overall and cardiovascular mortality., Results: Two percent (n = 227) of players were deceased, with a median age at death of 38 yr (range, 23-61 yr). The most common major causes of death were diseases of the heart (n = 47; 21%), violence (n = 39; 17%), and transportation injuries (n = 34; 15%). Risk of death was significantly lower than the general population for overall mortality (SMR, 0.46, 95% confidence interval (CI), 0.40-0.52), cardiovascular disease (SMR, 0.65; 95% CI, 0.50-0.84), and other major causes. Players with playing-time body mass index (BMI) of >35 kg·m had significantly higher cardiovascular disease mortality (SMR, 2.20; 95% CI, 1.32-3.44) than did the general population and higher overall mortality risk (standardized rate ratio, 3.84; 95% CI, 2.66-5.54) than did players with a BMI of <30 kg·m., Conclusions: Consistent with an earlier NFL cohort and other elite athlete populations, the overall and cardiovascular mortality risk of this NFL cohort was significantly lower than that of the general US male population, likely attributable to a healthy worker effect and less smoking.However, players with the highest playing-time BMI exhibited elevated cardiovascular mortality risk.

Previous findings suggest that professional American football players have higher blood pressures (BP) and a higher prevalence of pre-hypertension and hypertension than the general population. We sought to determine whether race is associated with differences in BP and prevalence of pre-hypertension and hypertension among a large sample of professional football players. BP was measured at 2009 team mini-camps for 1484 black (n = 1007) and white (n = 477) players from 27 National Football League (NFL) teams. Players were categorized into three position groups based on body mass index (BMI). There was no racial difference in mean systolic or diastolic BP in any of the three position groups. There were no racial differences in prevalence of hypertension (99 [9.8%] black players vs. 39 [8.2%] white players; P = .353) or pre-hypertension (557 [55.3%] black players vs. 264 [55.3%] white players; P = 1.0). Contrary to findings in the general population, BP and prevalence of pre-hypertension/hypertension did not vary with race in a large population of active NFL players., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Retired National Football League (NFL) linemen have an increased prevalence of risk factors for atherosclerosis and have an increased risk of cardiovascular death compared with nonlinemen and the general population. We evaluated whether playing in lineman position is independently associated with an increased risk of the presence and severity of subclinical atherosclerosis. Players were categorized as linemen if they reported playing on the offensive or defensive line during their careers. Subclinical atherosclerosis was assessed using coronary artery calcium (CAC) scores in 931 retired NFL players (310 linemen, 621 nonlinemen). CAC scores were evaluated for absence of subclinical atherosclerosis (CAC = 0), presence of mild subclinical atherosclerosis (CAC 1 to 100), and moderate to severe subclinical atherosclerosis (CAC ≥100). We performed multivariate logistic regression to determine whether the lineman position is independently associated with the presence and severity of subclinical atherosclerosis. Linemen were noted to have a lesser likelihood of absence of subclinical atherosclerosis (CAC = 0, 33.8% vs 41.7%, p = 0.02), a similar likelihood of mild subclinical atherosclerosis (CAC 1 to 100, 33.2% vs 31.8%, p = 0.7), and a greater likelihood of moderate to severe subclinical atherosclerosis (CAC >100, 32.9% vs 26.4%, p = 0.04) compared with nonlinemen. Adjusting for demographic and metabolic covariates, lineman status remained independently associated with mild subclinical atherosclerosis (CAC 1 to 100, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.05 to 2.2, p = 0.04) and moderate to severe subclinical atherosclerosis (CAC ≥100, OR 1.67, 95% CI 1.05 to 2.2). The association was attenuated after adjustment for race (CAC 1 to 100, OR 1.24, 95% CI 0.82 to 1.8; CAC >100, OR 1.59, 95% CI 1.01 to 2.49). In conclusion, lineman status in retired NFL players is associated with presence and severity of subclinical atherosclerosis, which is partly explained by race., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: It is unknown which measure of adiposity (body mass index [BMI] or waist circumference [WC]) is associated with subclinical atherosclerosis in retired National Football League (NFL) players and whether this relation is attenuated after adjusting for components of the metabolic syndrome (elevated triglycerides, fasting glucose, and low levels of high-density lipoprotein-cholesterol [HDL-C]) that frequently coexist with obesity., Methods: Coronary artery calcium (CAC) was measured in 926 retired NFL players. BMI was calculated as weight (in kilograms)/height (in meters)(2) and WC was measured in inches. Logistic regression analyses adjusting for age, race, systolic blood pressure, high sensitivity C-reactive protein, triglycerides, HDL-C, and fasting blood glucose were performed to evaluate whether BMI or WC was independently associated with the presence of CAC (CAC score >0)., Results: The median age, BMI and WC were 54 years, 31 kg/m(2), and 40 inches, respectively. CAC was present in 61% (n = 562) of retired players. Adjusting for age, race, systolic blood pressure, high sensitivity C-reactive protein, triglycerides, HDL-C, and fasting blood glucose, each standard deviation increase in BMI (4.85 kg/m(2)) was significantly associated with CAC (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.03-1.50), but each standard deviation increase in WC (10.53 inches) was not significantly associated with CAC (OR 1.18, 95% CI 0.96-1.45). There was a significant association for the presence of CAC for highest versus lowest quartiles of both BMI (OR 1.93, 95% CI 1.13-3.28) and WC (OR 1.75, 95% CI 1.05-2.92), although the trend for the presence of CAC was significant only across increasing BMI quartiles, even in models that included WC., Conclusions: In retired NFL players both BMI and WC were associated with CAC. Higher BMI may be associated with an increasing trend for the presence of CAC independent of WC.

Despite the efficacy of statin therapy, patients treated with these agents face substantial residual risk that is associated with achieved levels of LDL cholesterol (LDL-C). These observations suggest a potential benefit of additional strategies to promote further LDL-C reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an attractive target in this regard. Abrogation of PCSK9 function prevents PCSK9-mediated catabolism of LDL receptors, increases cell surface LDL receptor density, and promotes clearance of LDL and other atherogenic lipoproteins from the circulation. Thus far, the most advanced approaches to block PCSK9 action are monoclonal antibodies and anti-sense oligonucleotides. Among statin-treated patients, these agents may produce additional LDL-C lowering exceeding 50 %. In rare genetic experiments of nature, individuals with dominant negative or dual loss of function mutations of PCSK9 appear to have no adverse health effects resulting from lifelong, very low levels of LDL-C. In short-term trials, PCSK9 antibodies have been generally well-tolerated. However, evidence to support long-term safety and efficacy of PCSK9 therapy to reduce cardiovascular risk awaits the results of large cardiovascular outcome trials.

A daily routine of physical activity is highly beneficial in the prevention and treatment of many prevalent chronic diseases, especially of the cardiovascular (CV) system. However, chronic, excessive sustained endurance exercise may cause adverse structural remodeling of the heart and large arteries. An evolving body of data indicates that chronically training for and participating in extreme endurance competitions such as marathons, ultra-marathons, Iron-man distance triathlons, very long distance bicycle racing, etc., can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which generally return to normal within seven to ten days. In veteran extreme endurance athletes, this recurrent myocardial injury and repair may eventually result in patchy myocardial fibrosis, particularly in the atria, interventricular septum and right ventricle, potentially creating a substrate for atrial and ventricular arrhythmias. Furthermore, chronic, excessive, sustained, high-intensity endurance exercise may be associated with diastolic dysfunction, large-artery wall stiffening and coronary artery calcification. Not all veteran extreme endurance athletes develop pathological remodeling, and indeed lifelong exercisers generally have low mortality rates and excellent functional capacity. The aim of this review is to discuss the emerging understanding of the cardiac pathophysiology of extreme endurance exercise, and make suggestions about healthier fitness patterns for promoting optimal CV health and longevity.

Objectives: We assessed whether low-density lipoprotein particle concentration (LDL-P) and high-sensitivity C-reactive protein [hs-CRP] can identify subclinical atherosclerosis better than traditional cholesterol parameters in retired National Football League (NFL) players., Background: It is not known whether LDL-P and the biomarker hs-CRP can identify subclinical atherosclerosis better than low-density lipoprotein cholesterol (LDL-C) or non-high-density-lipoprotein cholesterol (non-HDL-C) in retired NFL players, given high prevalence of metabolic syndrome in these players., Methods: Carotid artery plaque screening was performed with traditional lipids, LDL-P, and hs-CRP in 996 retired players. Logistic regression analyses comparing highest with the lowest quartile were performed., Results: Carotid artery plaques were seen in 41%. LDL-C (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.06-2.59), non-HDL-C (OR 1.67, 95% CI 1.04-2.67), and LDL-P (OR 2.21, 95% CI 1.35-3.62) were associated with plaques in adjusted models. Among 187 retired players with metabolic syndrome, LDL-C (OR 1.40, 95% CI 0.53-3.72) was not associated with carotid plaques, whereas LDL-P (OR 3.71, 95% CI 1.16-11.84) and non-HDL-C (OR 2.63, 95% CI 0.91-7.63, p=0.07; borderline significant) were associated with carotid plaques. hs-CRP (OR 1.13, 95% CI 0.71-1.79) was not associated with carotid plaques., Conclusion: Carotid artery plaques were common in retired NFL players and were strongly associated with LDL-P, especially among those with metabolic syndrome. hs-CRP was not associated with carotid plaques in this cohort., (Published by Elsevier Ireland Ltd.)

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity., (Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The US Air Force Patient-Centered Precision Care Genomic Medicine Research Program hosted a symposium entitled 'Changing the Health Care Paradigm' on 27 September 2011 in Laurel, MD, USA. The program provided a unique opportunity for subject matter experts to participate in critical discussions on the current and potential outlook for the implementation of genome-informed healthcare. The implications for patient privacy, data management and security revealed the ethical, legal and social issues faced by clinicians, patients and policy-makers. Highlights from these discussions are summarized in this article.

Circulating levels of inflammatory markers predict the risk of cardiovascular disease (CVD), mediated perhaps in part by dietary fat intake, through mechanisms only partially understood. To evaluate post-fat load changes in inflammatory markers and genetic influences on these changes, we administered a standardized high-fat meal to 838 related Amish subjects as part of the Heredity and Phenotype Intervention (HAPI) Heart Study and measured a panel of inflammatory markers, including C-reactive protein (CRP), interleukin-1beta (IL-1beta), matrix metalloproteinase-1 and -9 (MMP-1 and MMP-9), and white blood cell (WBC) count, before and 4 h after fat challenge (CRP prechallenge only). Heritabilities (h(2) +/- s.d.) of basal inflammatory levels ranged from 16 +/- 8% for MMP-9 (P = 0.02) to 90 +/- 7% for MMP-1 (P < 0.0001). Post-fat load, circulating levels of WBC, MMP-1, and MMP-9 increased by 16, 32, and 43% (all P < 0.0001), with no significant changes in IL-1beta. Postprandial changes over the 4-h period were modestly heritable for WBC (age- and sex-adjusted h(2) = 14 +/- 9%, P = 0.04), but the larger MMP-1 and MMP-9 changes appeared to be independent of additive genetic effects. These results reveal that a high-fat meal induces a considerable inflammatory response. Genetic factors appear to play a significant role influencing basal inflammatory levels but to have minimal influence on post-fat intake inflammatory changes.

Aims: We characterized the size of active National Football League (NFL) players by multiple criteria and analyzed their relation to traditional cardiovascular disease (CVD) risk factors with the objective of further clarifying the occurrence of cardiovascular risk factors in different player positions., Methods: This cross-sectional study was conducted in professional athletic training facilities. The participants were 504 active veteran players from a convenience sample of 12 NFL teams, grouped as interior linemen (IL) or all others (AO). Comparisons were made between the NFL groups and an age-equivalent general population database., Results: The IL group was significantly larger than AO by all size measures. Both groups were significantly larger than the Coronary Artery Risk Development in Young Adults (CARDIA) group. Mean percent body fat measurements in AO (mean, 13.4%; 95% confidence interval [CI], 12.9%-14%) and IL (mean, 25.2%; 95% CI, 24.4%-26%) groups were lower than estimates for the general population. Systolic blood pressure (BP) was higher in IL (mean, 131 mm Hg; 95% CI, 129-133 mm Hg) than AO (mean, 126 mm Hg; 95% CI, 125-127 mm Hg) and greater in both groups compared with the CARDIA group (mean, 112 mm Hg; 95% CI, 111-112 mm Hg). Mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, and glucose were within the normal range for both IL and AO. Interior linemen had significantly lower HDL-C than AO and the CARDIA group. Both NFL groups had significantly lower fasting glucose than CARDIA., Conclusion: Body fat in active NFL players was lower than predicted by standard measures of obesity. Although the players were large, they were in the normal range for most CVD risk factors. Mean BP in the prehypertensive range was found in both NFL position groups, but was significantly higher in IL than in AO. Prehypertension in these athletes warrants vigilance.

Context: Concern exists about the cardiovascular health implications of large size among professional football players and those players who aspire to professional status., Objectives: To assess cardiovascular disease (CVD) risk factors in active National Football League (NFL) players and to compare these findings with data from the Coronary Artery Risk Development in Young Adults (CARDIA) study., Design, Setting, and Participants: A cross-sectional study of 504 active, veteran football players from a convenience sample of 12 NFL teams at professional athletic training facilities between April and July 2007. Data were compared with men of the same age in the general US population (CARDIA study, a population-based observational study of 1959 participants aged 23 to 35 years recruited in 1985-1986)., Main Outcome Measures: Prevalence of CVD risk factors (hypertension, dyslipidemia, glucose intolerance, and smoking)., Results: The NFL players were less likely to smoke when compared with the CARDIA group (0.1% [n = 1]; 95% confidence interval [CI], 0%-1.4%; vs 30.5% [n = 597]; 95% CI, 28.5%-32.5%; P < .001). Despite being taller and heavier, NFL players had significantly lower prevalence of impaired fasting glucose (6.7% [n = 24]; 95% CI, 4.6%-8.7%; vs 15.5% [n = 267]; 95% CI, 13.8%-17.3%; P < .001). The groups did not differ in prevalence of high total cholesterol and low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), or high triglycerides. Hypertension (13.8% [n = 67]; 95% CI, 11.0%-16.7%; vs 5.5% [n = 108]; 95% CI, 4.6%-6.6%) and prehypertension (64.5% [n = 310]; 95% CI, 58.3%-70.7%; vs 24.2% [n = 473]; 95% CI, 22.3%-26.1%) were significantly more common in NFL players than in the CARDIA group (both P < .001). Large size measured by body mass index (BMI) was associated with increased blood pressure, LDL-C, triglycerides, and fasting glucose, and decreased HDL-C., Conclusions: Compared with a sample of healthy young-adult men, a sample of substantially larger NFL players had a lower prevalence of impaired fasting glucose, less reported smoking, a similar prevalence of dyslipidemia, and a higher prevalence of hypertension. Increased size measured by BMI was associated with increased CVD risk factors in this combined population.

Although popular diets focus on weight loss and their favorable biochemical and physiological effects, fewer investigations have evaluated the biological impact of these diets during weight maintenance. To study this issue, three popular diets-Atkins, South Beach, and Ornish-were tested in a randomized and counterbalanced crossover study between January and December 2006. Participants completed each of the three 4-week isocaloric dietary intervention phases followed by a 4-week washout period. They were weighed weekly and caloric adjustments made if weight change exceeded 1 kg. At the completion of each dietary phase, 3-day food records were analyzed, fasting blood sampled, and brachial artery reactivity testing performed. Eighteen adults completed all three isocaloric dietary phases. During the South Beach and Ornish maintenance phase, there were significant reductions in low-density lipoprotein cholesterol (11.8%; P=0.01, 16.6%; P=0.0006, respectively) compared to prediet baseline. In addition, in contrast to the Atkins maintenance phase, significant reductions in low-density lipoprotein cholesterol and apolipoprotein B levels were observed after the South Beach (P=0.003, P=0.05; repeated measures analyses of variance) and Ornish maintenance phases (P=0.0004, P=0.006, repeated measures analyses of variance). Brachial artery testing revealed an inverse correlation between flow-mediated vasodilatation and intake of saturated fat (r=-0.33; P=0.016). These data suggest that during weight maintenance, less favorable biological effects are observed during a simulated, high-fat Atkins diet when compared to the South Beach and Ornish diet. The findings support additional study in subjects with visceral obesity and the metabolic syndrome, in whom an increased risk of coronary disease at baseline may be accentuated with chronic consumption of a diet that exhibits unfavorable effects on lipids and endothelial function.

Objective: Recent clinical trials and observational studies have suggested that reduction in low-density lipoprotein cholesterol (LDL-C) does not account for all differences among statins' effects on cardiovascular (CV) events, but that these effects may vary with time. Using a large US managed-care claims data set for 2002-2005, we assessed whether a difference in the rate of inpatient CV event rates could be observed between new atorvastatin and simvastatin users taking doses with comparable LDL-C-lowering potency, when prior risk factors are controlled and varying observation periods are employed., Research Design and Methods: Eligible patients had a 6-month period of no statin use prior to the initial statin prescription, an initial statin dosage of either 20 or 40 mg of simvastatin or 10 or 20 mg of atorvastatin (the most commonly used doses of both drugs), a 0 to 3-month 'qualifying period' after the first prescription to allow for varying minimum lengths of statin use, and no statin switches. In the primary analysis, patients were observed until an event or significant non-adherence occurred, up to 3.5 years; in secondary analyses, maximum 3-month, 6-month and 1-year observation periods were used. The primary endpoint was the first inpatient admission due to a CV event after the end of the qualifying period; multivariate Cox regression analysis controlled for a variety of demographic and CV risk characteristics and statin type., Results: At baseline, simvastatin users had significantly higher observed risk factors and higher subsequent, unadjusted CV event rates. In the primary Cox regression analyses, the CV event hazard rates for atorvastatin ranged from 0.899 (1-month qualifying period, p = 0.027) to 0.936 (3-month qualifying period, p = 0.33) versus simvastatin. Cox-based hazard rates for atorvastatin during 3-month to 1-year observation periods ranged from 0.908 to 0.915 for the 0-day qualifying period and from 0.851 to 0.884 for the 1-month qualifying period cohort (all p < 0.05); rates for the 3-month qualifying period cohort remained non-significant., Limitations: Since this was not a prospective randomized study, there is the potential for unobserved risk factors to be responsible for some or all of the differences observed., Conclusions: These results indicate an association between atorvastatin use and lower CV event rates, particularly in the first year of use, when observable risk factor differences are controlled. The implied absolute risk reduction of 2-3 events per 1000 patients per year may be considered clinically significant when viewed relative to major clinical trial results.

Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, hypertension, and heart failure. The endothelium mediates vascular tone, structure, and function by the release and regulation of multiple vasoactive substances that promote or inhibit vasodilation, vasoconstriction, cell growth, and other mechanisms. The effect of antihypertensive drugs on endothelial function may be an important indicator of their ability to reduce risks for cardiovascular morbidity and mortality. Endothelium-dependent vasodilation induced by various antihypertensive drugs is accurately measured with high-resolution ultrasound of flow-mediated dilation of the brachial artery. Calcium channel blockers and angiotensin-converting enzyme inhibitors have been shown to reverse endothelial dysfunction. The benefits of angiotensin-converting enzyme inhibitors and calcium channel blockers on the endothelium are believed to derive from their effects on nitric oxide production and antioxidant effects, possibly independent of blood pressure reduction. Due to their complementary mechanisms of action, it has been hypothesized that the combination of an angiotensin-converting enzyme inhibitor and a calcium channel blocker will provide superior cardiovascular protection, in part by producing an additive effect of increased nitric oxide availability, when compared with either agent alone.

Evidence suggests that renin-angiotensin-aldosterone system inhibition ameliorates endothelial dysfunction. The authors examined the effect of amlodipine besylate/benazepril HCl combination treatment compared with amlodipine besylate monotherapy in modulating endothelial dysfunction. This multicenter, double-blind, 12-week study randomized 70 hypertensive subjects with at least one other endothelial dysfunction risk factor to amlodipine besylate/benazepril HCl (5/20 mg/d force-titrated to 5/40 mg/d) or amlodipine besylate monotherapy (5 mg/d force-titrated to 10 mg/d). Both the combination and monotherapy produced significant median increases from baseline in percentage flow-mediated vasodilation (2.0% and 1.2%, respectively) and percentage change in percent flow-mediated vasodilation (25% and 16%, respectively). These improvements were numerically larger with combination treatment, but between-group differences did not achieve statistical significance. Reductions in systolic and diastolic blood pressure were significantly greater (P=.0452/P=.0297) with combination treatment (-18.6/-12.3 mm Hg) than with monotherapy (-14.8/-9.1 mm Hg). A highly positive correlation between change in systolic blood pressure and change in percent of flow-mediated vasodilation was demonstrated only for combination treatment.