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1.  sRAGE and the risk for incident heart failure: The Atherosclerosis Risk in Communities Study 
American heart journal  2015;170(5):961-967.
Experimental studies in animals suggest that circulating soluble receptor for advanced glycation end-products (sRAGE) decrease oxidative stress, inflammation and fibrosis. The association between sRAGE and incident heart failure has not been systematically examined in a prospective study.
We conducted a prospective analysis of a subsample of 1,086 participants from the Atherosclerosis Risk in Communities Study who attended visit 2 (1990–1992) without a history of coronary heart disease, stroke, or heart failure and with measured plasma sRAGE levels. Incident heart failure was defined as death from heart failure or hospitalization due to heart failure during a median of 20 years of follow up.
In this sample of a community-based population (mean age 63 years, 60% women, 78% white), there were 126 incident cases of heart failure. Lower levels of sRAGE were significantly associated with an increased risk of heart failure; the adjusted hazard ratios (95% confidence intervals) of heart failure were 1.0 (reference), 1.81 (0.94–3.49), 1.57 (0.80–3.08) and, 3.37 (1.75–6.50), for 4th, 3rd, 2nd and 1st quartile respectively (P for trend=0.001). We did not observe significant interactions by diabetes status or by race or obesity status.
Lower circulating levels of sRAGE are independently associated with the development of heart failure in a community-based population. Our results add to the growing evidence that sRAGE is a valuable predictor of cardiovascular disease.
PMCID: PMC4638130  PMID: 26542505
2.  Periaortic Fat and Cardiovascular Risk: A Comparison of High-Risk Older Adults and Age-Matched Healthy Controls 
Fat accumulation around the heart and aorta may impact cardiovascular (CV) health. The purpose of this study was to conduct a systematic investigation to examine potential associations of these fat depots with risk factors for CV events, which has not been done before.
Pericardial fat, periaortic fat around the ascending aorta (AA), descending aorta (DA) and aortic arch, and abdominal subcutaneous and visceral fat were measured by MRI in older adults with (n=385, 69±8 years, 52% female) and without (n=50, 69±8 years, 58% female) risk factors for a CV event.
Individuals with CV risk factors exhibited greater fat volumes across all fat depots compared to those without risk factors. In analysis of covariance accounting for age, gender, race/ethnicity, diabetes, hypertension, coronary artery disease, smoking, and BMI, individuals with risk factors possessed higher epicardial, pericardial, AA, DA, and abdominal visceral fat (p<0.05). When matched one-to-one on age, gender, race/ethnicity, and BMI, AA and DA fat were higher in those with versus without CV risk factors (p<0.01).
Older adults with a high risk for CV events have greater periaortic fat than low-risk adults, even after accounting for BMI. More studies are needed to determine whether greater periaortic fat predicts future CV events.
PMCID: PMC4143481  PMID: 24525960
pericardial fat; periaortic fat; aging; cardiovascular risk
3.  Increased Cardiovascular Stiffness and Impaired Age-related Functional Status 
Our objective was to determine if increased cardiovascular (CV) stiffness is associated with disability in middle-aged and older adults at risk for congestive heart failure. CV stiffness (brachial pulse pressure/left ventricular stroke volume indexed to body surface area) and total disability (the summed assessment of activities of daily living, mobility, and instrumental activities of daily living) were measured in 445 individuals. A subset of 109 randomly selected individuals also underwent physical function testing. Total disability was associated with CV stiffness (p = .01), driven by an association with mobility (p = .005), but not activities of daily living (p = .13) or instrumental activities of daily living (p = .61). After accounting for age, these correlations remained significant for men (p = .04), but not for women. CV stiffness was also associated with increased 400-m walk time (p = .02). In middle-aged and elderly men at risk for congestive heart failure, CV stiffness is associated with decreased mobility and physical function, and increased overall disability.
PMCID: PMC4400394  PMID: 24963155
Cardiovascular stiffness; Disability; Congestive heart failure.
4.  Heterogeneity of Physical Function Responses to Exercise Training in Older Adults 
To describe the inter-individual variability in physical function responses to supervised, resistance and aerobic exercise training interventions in older adults.
Ninety-five older (65–79 years), overweight and obese (body mass index [BMI] ≥27 kg/m2), sedentary men and women.
Five-months of either 4 d/wk of aerobic training (AT, n=40) or 3 d/wk of resistance training (RT, n=55).
Physical function assessments: global measure of lower extremity function (short physical performance battery; SPPB), 400-meter walk, peak aerobic capacity (VO2peak), and knee extensor strength.
On average, both exercise interventions significantly improved physical function. For AT, there was a 7.9% increase in VO2peak; individual absolute increases varied from 0.4–4.3 ml/kg/min and four participants (13%) showed no change or a decrease in VO2peak. For RT, knee extensor strength improved an average of 8.1%, but individual increases varied from 1.2–63.7 Nm, and 16 participants (30%) showed no change or a decrease in strength. Majority of participants improved 400-m walk time, usual gait speed, chair rise time, and SPPB with AT, and improved usual gait speed, chair rise time, and SPPB with RT; but, there was wide variation in the magnitude of improvement. Compliance was only related to change in 400-m walk time following RT (r= −0.31; p<0.05).
Despite sufficient levels of adherence to both exercise interventions, some participants did not improve function, and the magnitude of improvement varied widely. Additional research is needed to identify factors that optimize responsiveness to exercise to maximize its functional benefits in older adults.
PMCID: PMC4373970  PMID: 25752778
aerobic training; resistance training; muscle strength; peak aerobic capacity; response variability
5.  Adiposity Is Associated with Gender-Specific Reductions in Left Ventricular Myocardial Perfusion during Dobutamine Stress 
PLoS ONE  2016;11(1):e0146519.
Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women.
Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress.
We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress.
Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men.
PMCID: PMC4709095  PMID: 26751789
6.  Pericardial Fat is Associated with Carotid Stiffness in the Multi-Ethnic Study of Atherosclerosis 
Background and Aims
Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5,770 participants (mean age 62 yrs, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.
Methods and Results
Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and young’s modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1-standard deviation (41.91 cm3) increment in Pfat was associated with a 0.00007±0.00002 1/mmHg lower DC (p=0.0002) in men and a 48.1±15.1 mmHg/mm higher YM in women (p=0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.
Higher Pfat is associated with higher carotid stiffness, independent of traditional CVD risk factors and obesity.
PMCID: PMC2929306  PMID: 20153618
pericardial fat; arterial stiffness; distensibility; carotid artery
7.  Caloric Restriction, Aerobic Exercise Training, and Soluble Lectin-like Oxidized LDL Receptor-1 Levels in Overweight and Obese Postmenopausal Women 
Elevated circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) have been observed in obese persons and are reduced by weight loss. However, it is not known if combining caloric restriction (CR) with exercise training is better in reducing sLOX-1 levels than CR alone.
We examined whether the addition of aerobic exercise to a weight loss intervention differentially affects sLOX-1 levels in 61 abdominally obese postmenopausal women randomly assigned to a CR only (n=22), CR + moderate-intensity exercise (n=22), or CR + vigorous-intensity exercise (n=17) intervention for 20 weeks. The caloric deficit was ~2,800 kcal/week for all groups.
The intervention groups were similar at baseline with respect to body weight, body composition, lipids, and blood pressure. However, plasma sLOX-1 levels were higher in the CR only group (99.90 ± 8.23 pg/ml) compared to both the CR + moderate-intensity exercise (69.39 ± 8.23 pg/ml, p=0.01) and CR + vigorous-intensity exercise (72.83 ± 9.36 pg/ml, p=0.03) groups. All three interventions significantly reduced body weight (~14%), body fat, and waist and hip circumferences to a similar degree. These changes were accompanied by a 23% reduction in sLOX-1 levels overall (−19.00 ± 30.08 pg/ml, p<0.0001), which did not differ among intervention groups (p=0.13). Changes in body weight, body fat, and VO2 max were not correlated with changes in sLOX-1 levels. In multiple regression analyses in all women combined, baseline sLOX-1 levels (β = − 0.70 ± 0.06, p<0.0001), age (β = 0.92 ± 0.43, p=0.03) and baseline BMI (β = 1.88 ± 0.66, p=0.006) were independent predictors of the change in sLOX-1 with weight loss.
Weight loss interventions of equal energy deficit have similar effects on sLOX-1 levels in overweight and obese postmenopausal women, with the addition of aerobic exercise having no added benefit when performed in conjunction with CR.
PMCID: PMC3023845  PMID: 20856256
obesity; weight loss; caloric restriction; aerobic exercise; soluble receptor
8.  Effect of ginkgo biloba on blood pressure and incidence of hypertension in elderly men and women 
American journal of hypertension  2010;23(5):528-533.
Accumulating evidence suggests that ginkgo biloba is cardioprotective, in part, through its vasodilatory and antihypertensive properties. However, definitive data on its blood pressure-lowering effects in humans is lacking.
We determined the effects of ginkgo biloba extract (240 mg/day) on blood pressure and incident hypertension in 3,069 participants (mean age, 79 yrs; 46% female; 96% White) from the Ginkgo Evaluation of Memory study. We also examined whether the treatment effects are modified by baseline hypertension status.
At baseline 54% of the study participants were hypertensive, 28% were pre-hypertensive, and 17% were normotensive. Over a median follow-up of 6.1 years, there were similar changes in blood pressure and pulse pressure in the ginkgo biloba and placebo groups. Although baseline hypertension status did not modify the antihypertensive effects of ginkgo biloba, it did influence the changes in blood pressure variables observed during follow-up, with decreases in hypertensives, increases in normotensives, and no changes in pre-hypertensives. Among participants who were not on antihypertensive medications at baseline, there was no difference between treatment groups in medication use over time, as the OR (95% CI) for being a never-user in the ginkgo biloba group was 0.75 (0.48–1.16). The rate of incident hypertension also did not differ between participants assigned to ginkgo biloba vs. placebo (HR, 0.99, 95% CI, 0.84–1.15).
Our data indicate that ginkgo biloba does not reduce blood pressure or the incidence of hypertension in elderly men and women.
PMCID: PMC2989407  PMID: 20168306
gingko biloba; blood pressure; hypertension; elderly
9.  Plasma Nitrate/Nitrite Levels are Unchanged after Long-Term Aerobic Exercise Training in Older Adults 
Reduced nitric oxide (NO) production and bioactivity is a major contributor to endothelial dysfunction. Animal data suggests that improvements in endothelial function in response to aerobic exercise training may depend on the duration of the training program. However, no studies have examined changes in NO (as assessed by the major NO metabolites, nitrate and nitrite, NOx) after long-term training in humans. In addition, aging may impair the ability of the vasculature to increase NO with exercise. Thus, we determined whether 24 weeks of aerobic exercise training increases plasma NOx levels in sedentary older adults. We also examined changes in forearm blood flow (FBF) at rest and during reactive hyperemia as a measure of vasomotor function. Plasma NOx levels were measured in 82 men and women using a modified Griess assay. FBF was assessed in a subset of individuals (n=15) using venous occlusion plethysmography. After 24 weeks of exercise training, there were significant improvements in maximum oxygen consumption, HDL cholesterol, triglycerides, and body fat. Changes in plasma NOx levels ranged from −14.83 to +16.69 μmol/L; however, the mean change overall was not significant (−0.33±6.30 μmol/L, p=0.64). Changes in plasma NOx levels were not associated with age, gender, race, HDL cholesterol, triglycerides, body weight, body fat, or maximal oxygen consumption. There were also no significant changes in basal FBF, peak FBF, hyperemic response, total hyperemic flow, or minimum forearm vascular resistance with exercise training. In conclusion, improvements in plasma NOx levels and FBF are not evident after long-term training in older adults.
PMCID: PMC2796424  PMID: 19825427
exercise training; nitric oxide; forearm blood flow; aging
10.  Plasma Oxidized Low-density Lipoprotein Levels and Arterial Stiffness in Older Adults: the Health ABC Study 
Hypertension  2009;53(5):846-852.
Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease (CVD). Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2,295 participants (mean age, 74 yrs; 52% female; 40% black) from the Health, Aging and Body Composition study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1, 869 ± 376 cm/s; tertile 2, 901 ± 394 cm/s; tertile 3, 938 ± 415 cm/s; p=0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional CVD risk factors (p=0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, anti-hypertensive and antilipemic medications, and CRP the association with ox-LDL was attenuated, but remained significant (p=0.01). Results were similar when ox-LDL was expressed in absolute (mg/dL) or relative amounts (percent of LDL). Moreover, individuals in the highest ox-LDL tertile were 30-55% more likely to have high arterial stiffness, defined as aPWV > 75th percentile (p≤0.02). In conclusion, we found that among elderly persons, elevated plasma ox-LDL levels are associated with higher arterial stiffness, independent of CVD risk factors. These data suggest that ox-LDL may be related to the pathogenesis of arterial stiffness.
PMCID: PMC2692957  PMID: 19332658
aging; epidemiology; aortic stiffness; pulse wave velocity; oxidative stress
11.  Chronic Inflammation Is Associated With Low Physical Function in Older Adults Across Multiple Comorbidities 
Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status.
We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands); inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP); and anthropometric measures.
Higher levels of CRP and IL-6, but not TNF-α, were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results.
Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.
PMCID: PMC2657165  PMID: 19196644
Inflammation; Physical function; Aging; Comorbidities
12.  Variation in the Lectin-like Oxidized LDL Receptor 1 (LOX-1) Gene Is Associated With Plasma Soluble LOX-1 Levels 
Experimental physiology  2008;93(9):1085-1090.
The lectin-like ox-LDL receptor 1 (LOX-1) expressed on vascular cells plays a major role in atherogenesis by internalizing and degrading oxidized LDL. LOX-1 can be cleaved from the cell surface and released as soluble LOX-1 (sLOX-1), and elevated sLOX-1 levels may be indicative of atherosclerotic plaque instability. We examined associations between the LOX-1 3′UTR-C/T and G501C polymorphisms and plasma sLOX-1 levels in 97 healthy older men and women. The frequencies for the 3′UTR-T and 501C alleles were 46% and 10%, respectively. Plasma sLOX-1 levels were significantly higher in the 3′UTR CC genotype group compared to both the CT (p=0.02) and TT (p=0.002) genotype groups. Plasma sLOX-1 were also significantly higher in the 501GC genotype group compared to the GG genotype group (p=0.004). In univariate analyses, sLOX-1 levels were significantly associated with both the 3′UTR-C/T and G501 C polymorphisms. These associations remained significant after adjusting for age, gender, race, and BMI. In conclusion, variation in the LOX-1 gene is associated with plasma sLOX-1 levels in older men and women.
PMCID: PMC2652129  PMID: 18469066
receptor; cardiovascular; gene expression
13.  Elevated Soluble Lectin-like Oxidized LDL Receptor 1 (LOX-1) Levels in Obese Postmenopausal Women 
Obesity (Silver Spring, Md.)  2008;16(6):1454-1456.
We investigated the association between soluble lectin-like oxidized LDL receptor 1 (sLOX-1) levels and obesity in older women. Fifty-one (10 lean, 22 overweight, and 19 obese) postmenopausal women were included in this small retrospective analysis. Plasma sLOX-1 levels were measured using a chemiluminescent ELISA. Plasma levels of sLOX-1 were significantly higher in obese women (55.33±4.49 pg/mL) compared to lean (30.91±6.19 pg/mL, p=0.002) and overweight women (38.31±4.18 pg/mL, p=0.017). Plasma sLOX-1 levels were positively associated with body weight, BMI, total body fat, and trunk fat. The relationship between sLOX-1 and BMI was attenuated after adjustment for age, HRT, and body fat. In conclusion, obese women have higher sLOX-1 levels, which may reflect increased LOX-1 expression in adipose tissue.
PMCID: PMC2677801  PMID: 18388896
obesity; postmenopausal women; receptors
14.  Intraperitoneal Fat Is Associated With Thickening of the Thoracic Aorta in Individuals at High Risk for Cardiovascular Events 
Obesity (Silver Spring, Md.)  2011;19(9):10.1038/oby.2011.188.
Increased intraperitoneal (IP) fat is associated with increased cardiovascular (CV) risk, but mechanisms for this increase in risk are not completely established. We performed this study to assess whether IP fat is associated with ascending aortic wall thickness (AOWT), a risk factor for CV events. Four hundred and forty-one consecutive participants, aged 55–85 years, with risk factors for CV events underwent magnetic resonance measures of AOWT and abdominal fat (subcutaneous (SC) fat + IP fat). For the ascending aorta, mean wall thickness of the 4th quartile of the IP fat was higher relative to the 1st quartile (P ≤ 0.001). This difference persisted after accounting for SC fat (P ≤ 0.001), as well as age, gender, height, weight, smoking, diabetes, hypertension, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and C-reactive protein (CRP) (P < 0.03). Elevated IP fat volume is associated with an increase in ascending AOWT, a condition that promotes CV events in middle aged and elderly adults.
PMCID: PMC3814164  PMID: 21720433
15.  Total and Abdominal Adiposity Are Associated With Inflammation in Older Adults Using a Factor Analysis Approach 
Obesity-related increases in multiple inflammatory markers may contribute to the persistent subclinical inflammation common with advancing age. However, it is unclear if a specific combination of markers reflects the underlying inflammatory state. We used factor analysis to identify inflammatory factor(s) and examine their associations with adiposity in older adults at risk for disability.
Adiponectin, CRP, IL-1ra, IL-1sRII, IL-2sRα, IL-6, IL-6sR, IL-8, IL-15, sTNFRI, sTNFRII, and TNF-α were measured in 179 participants from the Lifestyle Interventions and Independence for Elders Pilot (Mean ± SD age 77 ± 4 years, 76% white, 70% women). Body mass index, waist circumference, and total fat mass were assessed by anthropometry and dual-energy x-ray absorptiometry.
IL-2sRα, sTNFRI, and sTNFRII loaded highest on the first factor (factor 1). CRP, IL-1ra, and IL-6 loaded highest on the second factor (factor 2). Factor 2, but not factor 1, was positively associated with 1-SD increments in waist circumference (β = 0.160 ± 0.057, p = .005), body mass index (β = 0.132 ± 0.053, p = .01), and total fat mass (β = 0.126 ± 0.053, p = .02) after adjusting for age, gender, race/ethnicity, site, smoking, anti-inflammatory medications, comorbidity index, health-related quality of life, and physical function. These associations remained significant after further adjustment for grip strength, but only waist circumference remained associated with inflammation after adjusting for total lean mass. There were no significant interactions between adiposity and muscle mass or strength for either factor.
Greater total and abdominal adiposity are associated with higher levels of an inflammatory factor related to CRP, IL-1ra, and IL-6 in older adults, which may provide a clinically useful measure of inflammation in this population.
PMCID: PMC3437966  PMID: 22451470
Aging; Adiposity; Inflammation; Muscle impairment; Factor analysis
Hypertension  2010;56(5):901-906.
Fat in the renal sinus (RS), a region of the kidney in which low pressure venous and lymphatic vessels are present, may indirectly influence blood pressure (BP). The purpose of this study was to assess the association between RS fat and control of BP upon receipt of antihypertensive medications.
Two hundred-five (205) participants aged 55 to 85 years at risk for cardiovascular (CV) events underwent magnetic resonance imaging assessments of abdominal and RS fat, measurement of blood pressure, and determination of the number of prescribed antihypertensive medications. Multivariable linear regression was used to determine associations between RS fat, blood pressure, and the number of prescribed antihypertensive medications.
Abdominal fat averaged (416 ± 160 cm3, median and interquartile range (IQR) of 396 cm3 and 308 to 518 cm3); intraperitoneal (IP) fat averaged (141 ± 73 cm3, median and IQR of 129 cm3 and 86 to 194 cm3); and RS fat averaged (4.6 ± 3.2 cm3, median and IQR of 4.2 cm3 and 2.2 to 6.6 cm3). After accounting for age, gender, height, body mass index (BMI), and IP fat, RS fat correlated with the number of prescribed antihypertensive medications (p=0.010), stage II hypertension (p=0.02), and renal size (p=<0.001).
In conclusion, after accounting for other body fat depots and risk factors for hypertension, renal sinus fat volume is associated with the number of prescribed antihypertensive medications and stage II hypertension. These results indicate that further studies are warranted to determine if fat accumulation in the renal sinus promotes hypertension.
PMCID: PMC3634339  PMID: 20837881
Renal sinus; intraperitoneal fat; hypertension; blood pressure; body mass index
17.  Effect of exercise training on chronic inflammation 
Persistent, sub-clinical inflammation, as indicated by higher circulating levels of inflammatory mediators, is a prominent risk factor for several chronic diseases, as well as aging-related disability. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. Physical exercise is well recognized as an important strategy for reducing the risk of chronic disease, and recent research has focused on its role in the improvement of the inflammatory profile. This review summarizes the evidence for and against the role of increasing physical activity in the reduction of chronic inflammation. Large population-based cohort studies consistently show an inverse association between markers of systemic inflammation and physical activity or fitness status, and data from several small-scale intervention studies support that exercise training diminishes inflammation. However, data from large, randomized, controlled trials designed to definitively test the effects of exercise training on inflammation are limited, and results are inconclusive. Future studies are needed to refine our understanding of the effects of exercise training on systemic low-grade inflammation, the magnitude of such an effect, and the amount of exercise necessary to elicit clinically meaningful changes in the deleterious association between inflammation and disease.
PMCID: PMC3629815  PMID: 20188719
inflammation; exercise; cytokines; acute phase proteins; physical activity
18.  Pericardial Fat and Myocardial Perfusion in Asymptomatic Adults from the Multi-Ethnic Study of Atherosclerosis 
PLoS ONE  2011;6(12):e28410.
Pericardial fat has adverse effects on the surrounding vasculature. Previous studies suggest that pericardial fat may contribute to myocardial ischemia in symptomatic individuals. However, it is unknown if pericardial fat has similar effects in asymptomatic individuals.
We determined the association between pericardial fat and myocardial blood flow (MBF) in 214 adults with no prior history of cardiovascular disease from the Minnesota field center of the Multi-Ethnic Study of Atherosclerosis (43% female, 56% Caucasian, 44% Hispanic). Pericardial fat volume was measured by computed tomography. MBF was measured by MRI at rest and during adenosine-induced hyperemia. Myocardial perfusion reserve (PR) was calculated as the ratio of hyperemic to resting MBF.
Gender-stratified analyses revealed significant differences between men and women including less pericardial fat (71.9±31.3 vs. 105.2±57.5 cm3, p<0.0001) and higher resting MBF (1.12±0.23 vs. 0.93±0.19 ml/min/g, p<0.0001), hyperemic MBF (3.49±0.76 vs. 2.65±0.72 ml/min/g, p<0.0001), and PR (3.19±0.78 vs. 2.93±0.89, p = 0.03) in women. Correlations between pericardial fat and clinical and hemodynamic variables were stronger in women. In women only (p = 0.01 for gender interaction) higher pericardial fat was associated with higher resting MBF (p = 0.008). However, this association was attenuated after accounting for body mass index or rate-pressure product. There were no significant associations between pericardial fat and hyperemic MBF or PR after multivariate adjustment in either gender. In logistic regression analyses there was also no association between impaired coronary vasoreactivity, defined as having a PR <2.5, and pericardial fat in men (OR, 1.18; 95% CI, 0.82–1.70) or women (OR, 1.11; 95% CI, 0.68–1.82).
Our data fail to support an independent association between pericardial fat and myocardial perfusion in adults without symptomatic cardiovascular disease. Nevertheless, these findings highlight potentially important differences between asymptomatic and symptomatic individuals with respect to the underlying subclinical disease burden.
PMCID: PMC3235122  PMID: 22174800
19.  Exercise Training as a Treatment for Chronic Inflammation in the Elderly 
Persistent, sub-clinical inflammation predisposes to chronic disease, as well as the development of sarcopenia and disability, in frail elderly. Thus, the inflammatory pathway is a potential target for interventions to reduce aging-related disease and disability. This article highlights emerging data suggesting that increasing physical activity could be effective for reducing chronic inflammation in the elderly.
PMCID: PMC2789351  PMID: 19955865
aging; sarcopenia; inflammation; cytokines; physical activity
20.  The relationship of oxidative stress and cholesterol with dipping status before and after aerobic exercise training 
Blood pressure  2009;18(4):171-179.
The purpose of this study was to examine the effects of aerobic exercise training (AEXT) on dipping status in pre-hypertensive and stage-1 hypertensive individuals. A secondary purpose was to evaluate whether AEXT alters oxidative stress and endothelial biomarkers correlated to dipping status.
Twenty-three subjects underwent 24-h ambulatory blood pressure monitoring at baseline and after 6 months of AEXT. AEXT consisted of training at 70% VO2max 3 days/week for 6 months. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol, oxidized LDL (ox-LDL), triglycerides, urinary and plasma nitric oxide end-products, superoxide dismutase and 8-iso-PGF2α were measured before and after AEXT. Statistically, ANOVA and linear regression were used.
Before and after AEXT, there were no significant differences between dippers and non-dippers in any of the biomarkers except for total cholesterol following AEXT. In a sub-analysis following AEXT, 14 subjects retained their original dipping status, five subjects changed from dippers to non-dippers and four subjects changed from non-dippers to dippers. Significant differences existed between these groups in changes in total and LDL-cholesterol, ox-LDL, 8-iso-PGF2α and % Dip.
Changes in cholesterol levels but not oxidative stress or endothelial biomarkers were related to changes in BP variables following AEXT in dippers and non-dippers.
PMCID: PMC2922419  PMID: 19544106
Aerobic exercise; ambulatory blood pressure monitoring; dipper; non-dipper; hypertension; oxidative stress
21.  Exercise Training, NADPH Oxidase p22phox Gene Polymorphisms, and Hypertension 
Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and Stage 1 hypertensives.
Ninety-four sedentary Pre and Stage 1 hypertensive adults underwent 6 months of aerobic exercise training at a level of 70% V̇O2max to determine whether the CYBA polymorphisms, C242T and A640G, were associated with changes in urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), urinary nitric oxide metabolites (NOx), and plasma total antioxidant capacity (TAC).
Demographic and subject characteristics were similar among genotype groups for both polymorphisms. At baseline, a significant (P = 0.03) difference among the C2424T genotype groups in 8-iso-PGF2α levels was detected, with the TT homozygotes having the lowest levels and the CC homozygotes having the highest levels. However, no differences were found at baseline between the A640G genotype groups. After 6 months of aerobic exercise training, there was a significant increase in V̇O2max (P < 0.0001) in the entire study population. In addition, there were significant increases in both urinary 8-iso-PGF2α (P = 0.002) and plasma TAC (P = 0.03) levels and a significant decrease in endogenous urinary NOx (P < 0.0001). Overall, aerobic exercise training elicited no significant differences among genotype groups in either CYBA variant for any of the oxidative stress variables.
We found that compared with CYBA polymorphisms C242T and A640G, it was aerobic exercise training that had the greatest influence on the selected biomarkers; furthermore, our results suggest that the C242T CYBA variant influences baseline levels of urinary 8-iso-PGF2α but not the aerobic exercise-induced responses.
PMCID: PMC2871250  PMID: 19516159

Résultats 1-21 (21)