Mechanisms Driving the Effect of Weight Loss on Arterial Stiffness

Aims Arterial stiffness decreases with weight loss in overweight and obese adults, but the mechanisms by which this occurs are poorly understood. We aimed to elucidate these mechanisms. Methods We evaluated carotid-femoral pulse wave velocity (cfPWV), a measure of aortic stiffness, and brachial-ankle pulse wave velocity (baPWV), a mixed measure of central and peripheral arterial stiffness, in 344 young adults (mean age 38 yrs, mean body mass index (BMI) 32.9 kg/m2, 23% male) at baseline, 6 and 12 months in a behavioral weight loss intervention. Linear mixed effects models were used to evaluate associations between weight loss and arterial stiffness and to examine the degree to which improvements in obesity-related factors explained these associations. Pattern-mixture models using indicator variables for dropout pattern and Markov Chain Monte Carlo multiple imputation were used to evaluate the influence of different missing data assumptions. Results At 6 months (7% mean weight loss from baseline), there was a statistically significant median decrease of 47.5 cm/s (interquartile range (IQR) -44.5, 148) in cfPWV (p<0.0001) and a mean decrease of 11.7 cm/s (standard deviation (SD) 91.4) in baPWV (p=0.049). At 12 months (6% mean weight loss from baseline) only cfPWV remained statistically significantly reduced from baseline (p=0.02). Change in BMI (p=0.01) was statistically significantly positively associated with change in cfPWV after adjustment for changes in mean arterial pressure (MAP) or any other measured obesity-related factor. Common carotid artery diameter (p=0.003) was associated and heart rate (p=0.08) and MAP (p=0.07) marginally associated longitudinally with cfPWV. Reductions in heart rate (p<0.0001) and C-reactive protein (p=0.02) were associated with reduced baPWV, and each removed the statistical significance of the effect of weight loss on baPWV. Pattern-mixture modeling revealed several differences between completers and non-completers in the models for cfPWV, but marginal parameter estimates changed little from the original models for either PWV measure. Conclusions The public health importance of this thesis is that firstly, weight loss improves arterial stiffness in overweight and obese young adults. Secondly, its effect on baPWV may be explained by concurrent reductions in heart rate and inflammation. Missing data did not appear to bias these results

Long-term health benefits and costs of measurement of carotid intima-media thickness in prevention of coronary heart disease

OBJECTIVE: Recently, it was demonstrated that information on carotid intima-media thickness (CIMT) and plaque may improve coronary heart disease (CHD) risk prediction through reclassification of some individuals to the correct risk category using the Framingham risk score. Our objective was to assess the currently unknown cost-effectiveness of CIMT measurements in primary prevention. METHODS: A hypothetical cohort of men and women aged 50-59 years and at intermediate or high CHD risk based on data from the Atherosclerosis Risk in Communities Study was simulated using a Markov model. Myocardial infarction (MI) events were used as a proxy for CHD. The effectiveness of pharmaceutical treatment was varied in the analysis. Sensitivity analysis was performed to obtain robust results. RESULTS: CIMT-based reclassification induced a 1% lower absolute risk of MI and 0.01-0.02 increase in quality-adjusted life years (QALYs) for men, and a 1-3% lower risk, and 0.03-0.05 increase in QALYs for women, over a period of 20-30 years. Corresponding costs were an additional $100 per man, and a cost-saving of$200-300 per woman. Over a 10-year period CIMT measurements were cost-effective with a probability of 66% (men), and 94% (women). Over a 30-year period, CIMT measurements had acceptable cost-effectiveness for men and women. CONCLUSION: Performing CIMT measurements in asymptomatic men and women aged 50-59 years results in additional, but small, health benefits. It takes time for these health benefits to outweigh the initial CIMT measurement costs. Our results support CIMT measurements for cardiovascular risk stratification, in particular for women, when focusing on long-term health

Comparison of SWAN and WISE Menopausal Status Classification Algorithms

Background: Classification of menopausal status is important for epidemiological and clinical studies as well as for clinicians treating midlife women. Most epidemiological studies, including the Study of Women's Health Across the Nation (SWAN), classify women based on self-reported bleeding history. Methods: The Women's Ischemia Syndrome Evaluation (WISE) study developed an algorithm using menstrual and reproductive history and serum hormone levels to reproduce the menopausal status classifications assigned by the WISE hormone committee. We applied that algorithm to women participating in SWAN and examined characteristics of women with concordant and discordant SWAN and WISE classifications. Results: Of the 3215 SWAN women with complete information at baseline (1995–1997), 2466 (76.7%) received concordant classifications (kappa = 0.52); at the fifth annual follow-up visit, of the 1623 women with complete information, 1154 (72.7%) received concordant classifications (kappa = 0.57). At each time point, we identified subgroups of women with discordant SWAN and WISE classifications. These subgroups, ordered by chronological age, showed increasing trends for menopausal symptoms and follicle-stimulating hormone (FSH) and a decreasing trend for estrogen (p < 0.001). Conclusions: The WISE algorithm is a useful tool for studies that have access to blood samples for hormone data unrelated to menstrual cycle phase, with or without an intact uterus, and no resources for adjudication. Future studies may want to combine aspects of the SWAN and WISE algorithms by adding hormonal measures to the series of bleeding questions in order to determine more precisely where women are in the perimenopausal continuum.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63232/1/jwh.2006.15.1184.pd

Relation of cardiovascular risk factors in women approaching menopause to menstrual cycle characteristics and reproductive hormones in the follicular and luteal phases

CONTEXT: Menstrual cycle characteristics may be associated with cardiovascular disease (CVD) risk. OBJECTIVE: The objective of this study was to describe the relationships between menstrual cycle characteristics and daily reproductive hormone measures with CVD risk factors in middle-aged women. DESIGN AND SETTING: Cross-sectional associations were examined between CVD risk factors and urinary LH, FSH, estrone conjugates, and pregnanediol glucuronide (Pdg) measured across one menstrual cycle or 50 d. PARTICIPANTS: Menstruating women (n = 500) who were free from diabetes or past stroke or heart attack enrolled in the Daily Hormone Study-Study of Women\u27s Health across the Nation were studied. MAIN OUTCOME MEASURES: Body mass index (BMI), blood pressure, hemostatic, and metabolic factors were measured. RESULTS: Few differences existed in risk factors between women with evidence of luteal activity and those with no evidence of luteal activity. Associations between elevated CVD risk factors and long cycle length were reduced substantially by age and BMI adjustments. Those with lower estrone conjugate and PdG averaged across the follicular phase had higher waist circumference, triglycerides, insulin, plasminogen activator inhibitor type-1, tissue type plasminogen activator-antigen, and factor VIIc levels in age- and BMI-adjusted analyses (P \u3c 0.05). CONCLUSIONS: In midlife menstruating women, a longer cycle length was related to CVD risk factors, in large part through their common association with BMI. More favorable levels of metabolic and hemostatic factors were associated with higher levels of follicular-phase estrogen, a pattern consistent with a more competent ovary, and higher levels of follicular-phase PdG, perhaps of adrenal origin. Metabolic and hemostatic factors may be sensitive to hormonal variation during the early perimenopausal transition

Relationship of ankle blood pressures to cardiovascular events in older adults.

BACKGROUND AND PURPOSE - Low values of ankle-arm systolic blood pressure ratio predict mortality and cardiovascular events. High values, associated with arterial calcification, also carry risk for mortality. We focus on the extent to which low and high ankle-arm index values as well as noncompressible arteries are associated with mortality and cardiovascular events, including stroke in older adults. METHODS - We followed 2886 adults aged 70 to 79 for a mean of 6.7 years for vital status and cardiovascular events (coronary heart disease, stroke, and congestive heart failure). RESULTS - Normal ankle-arm index values of 0.91 to 1.3 were found in 80%, low values of ≤0.9 were found in 13%, high values of >1.3 were obtained in 5%, and noncompressible arteries were found in 2% of the group. Increased mortality was associated with both low and high ankle-arm index values beginning at levels of <1.0 or ≥1.4. Subjects with low ankle-arm index values or noncompressible arteries had significantly higher event rates than those with normal ankle blood pressures for all end points. For coronary heart disease, hazard ratios associated with a low ankle-arm index, high ankle-arm index, and noncompressible arteries were 1.4, 1.5, and 1.7 (P<0.05 for all) after controlling for age, gender, race, prevalent cardiovascular disease, diabetes, and major cardiovascular risk factors. Noncompressible arteries carried a particularly high risk of stroke and congestive heart failure (hazard ratio=2.1 and 2.4, respectively). CONCLUSIONS - Among older adults, low and high ankle-arm index values carry elevated risk for cardiovascular events. Noncompressible leg arteries carry elevated risk for stroke and congestive heart failure specifically. © 2008 American Heart Association, Inc

Complement protein C3 and coronary artery calcium in middle-aged women with polycystic ovary syndrome and controls

Circulating complement protein C3 (C3) levels have been associated with coronary artery calcification (CAC) in women with systemic lupus erythematosus, but have yet to be evaluated in women with polycystic ovary syndrome (PCOS). We aimed to determine whether C3 levels were elevated in women with PCOS compared to controls, and to quantify the association of C3 with cardiovascular disease (CVD) risk factors and CAC, and if PCOS modified this association. This cross-sectional analysis included 132 women with PCOS and 155 controls 35-62 years old from the third visit of a case-control study. CAC was measured during the study visit and circulating C3 was measured in stored sera. The presence of CAC and CAC categories (Agatston score 0, 1-9.9, and ≥10) were used for logistic and ordinal regression analysis, respectively. C3 levels were not significantly different between women with PCOS and controls. Among all women, C3 was associated with the presence of CAC and increasing CAC groups after adjusting for age, PCOS status, and insulin or BMI, all p<0.05. In addition, C3 was associated with the presence of CAC after adjusting for age, PCOS status, BMI, insulin and African American race, p=0.049. PCOS status did not modify these associations. In conclusion, circulating C3 levels may prove beneficial in identifying women at risk of CVD in women with PCOS and the general population

Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features

BACKGROUND: SHBG and liver enzymes levels are both associated with the risk of type 2 diabetes. However, the relationship between SHBG with liver enzymes and intrahepatic fat content remain poorly understood. OBJECTIVE: To investigate whether SHBG is correlated with glucose and lipids levels and whether this association depends on fatty liver content, liver enzymes or sex hormone concentrations. DESIGN AND PATIENTS: We studied 233 dysmetabolic men with measures of plasma SHBG, total testosterone, 17β-oestradiol, glucose, adiponectin, liver enzymes and hepatokines. Intrahepatic liver fat and visceral fat contents were measured by magnetic resonance imaging in 108 of these individuals. RESULTS: After adjustment for age, SHBG concentration was inversely correlated with fasting glucose (βstandardized  = -0·21, P = 0·0007), HbA1c (βstandardized  = -0·27, P &lt; 0·0001), triglycerides (βstandardized  = -0·19, P = 0·003) and positively correlated with HDL-Cholesterol (βstandardized  = 0·14, P = 0·03). These correlations persisted after adjustment for either total testosterone or 17β-oestradiol levels. SHBG was not related to either fetuin A or FGF 21 concentrations. The inverse association of SHBG with HbA1c and glycaemia was not altered after adjusting for liver markers but was no longer significant after adjustment for hepatic fat content. CONCLUSION: The significant association between SHBG and fasting glycaemia, HbA1c and lipid levels in dysmetabolic men was not related to either sex hormones or markers of liver function, but was dependent on intrahepatic fat. This suggests that intrahepatic fat, but not alterations in liver function markers, may be involved in the association between SHBG and glucose and lipid metabolism

Digital arterial pressure pulse wave analysis and cardiovascular events in the general population:the Prevention of Renal and Vascular End-stage Disease study

BACKGROUND: Arterial stiffness influences the contour of the digital pressure pulse wave. METHOD: Here, we investigated whether the digital pulse propagation index (DPPI), based on the digital pressure pulse wave, DPPI is associated with cardiovascular events, heart failure, and mortality in a large population-based cohort. Between 2001 and 2003, DPPI was measured with a PortaPres noninvasive hemodynamic monitoring device (FinaPres Medical Systems, Amsterdam, The Netherlands) in participants of the Prevention of Renal and Vascular End-stage Disease study, a community-based cohort. We assessed the main determinants of the DPPI and investigated associations of DPPI with cardiovascular events and mortality. RESULTS: The study included 5474 individuals. Mean age was 52.3 ± 11.8 years and 50.5% was male. Median baseline DPPI was 5.81 m/s (interquartile range 5.47-6.20). Higher age, mean arterial blood pressure, body height, heart rate, current smoking, and lower HDL cholesterol levels and waist circumference were independent determinants of the DPPI (r = 0.43). After adjustment for heart rate, highlogDPPI was associated with all-cause mortality [hazard ratio: 1.67, 95% confidence interval (1.55-1.81) per SD; P &lt; 0.001], cardiovascular mortality [hazard ratio 1.95 (1.72-2.22); P &lt; 0.001], and incident heart failure with reduced ejection fraction [hazard ratio 1.81 (1.60-2.06); P &lt; 0.001]. These associations remained independent upon further adjustment for confounders. Optimal cutoff values for DPPI ranged between 6.1 and 6.3 m/s for all endpoints. After multivariable adjustment, DPPI was no longer associated with coronary artery disease events or cerebrovascular events. CONCLUSION: The DPPI is associated with an increased risk of development of new onset heart failure with reduced ejection fraction and all-cause and cardiovascular mortality, but not with coronary artery events or cerebrovascular events.</p