Center for Cardiovascular Disease Prevention

Houston, TX, United States

Center for Cardiovascular Disease Prevention

Houston, TX, United States

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Lopez F.L.,University of Minnesota | Agarwal S.K.,University of North Carolina at Chapel Hill | MacLehose R.F.,University of Minnesota | Soliman E.Z.,Wake forest University | And 5 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2012

Background-Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid-lowering medication use with AF risk. Methods and Results-We analyzed 13 969 participants (25% African American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities study. Fasting high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987-1989) and each of 3 follow-up visits. The incidence of AF was ascertained through 2007. The association of the use of statins and other lipid-lowering medications with AF was estimated in 13 044 Atherosclerosis Risk in Communities participants attending visit 2 (1990 -1992), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years, there were 1433 incident AF cases. Multivariable hazard ratios (HRs) and 95% CIs of AF associated with a 1-SD increase in lipid levels were as follows: HDLc, 0.97 (0.91-1.04); LDLc, 0.90 (0.85- 0.96); total cholesterol, 0.89 (0.84-0.95); and triglycerides, 1.00 (0.96 -1.04). Participants taking lipid-lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82-1.13) compared with those not taking medications, whereas those taking statins had an adjusted HR of 0.91 (0.66 -1.25) compared with those taking other lipid-lowering medications. Conclusions-Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. However, HDLc and triglycerides were not independently associated with AF incidence. No association was found between the use of lipid-lowering medications and incident AF. © 2012 American Heart Association, Inc.


Nambi V.,Baylor College of Medicine | Nambi V.,Center for Cardiovascular Disease Prevention | Chambless L.,University of North Carolina at Chapel Hill | Folsom A.R.,University of Minnesota | And 7 more authors.
Journal of the American College of Cardiology | Year: 2010

Objectives: We evaluated whether carotid intima-media thickness (CIMT) and the presence or absence of plaque improved coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). Background: Traditional CHD risk prediction schemes need further improvement as the majority of the CHD events occur in the "low" and "intermediate" risk groups. On an ultrasound scan, CIMT and presence of plaque are associated with CHD, and therefore could potentially help improve CHD risk prediction. Methods: Risk prediction models (overall, and in men and women) considered included TRF only, TRF plus CIMT, TRF plus plaque, and TRF plus CIMT plus plaque. Model predictivity was determined by calculating the area under the receiver-operating characteristic curve (AUC) adjusted for optimism. Cox proportional hazards models were used to estimate 10-year CHD risk for each model, and the number of subjects reclassified was determined. Observed events were compared with expected events, and the net reclassification index was calculated. Results: Of 13,145 eligible subjects (5,682 men, 7,463 women), ∼23% were reclassified by adding CIMT plus plaque information. Overall, the CIMT plus TRF plus plaque model provided the most improvement in AUC, which increased from 0.742 (TRF only) to 0.755 (95% confidence interval for the difference in adjusted AUC: 0.008 to 0.017) in the overall sample. Similarly, the CIMT plus TRF plus plaque model had the best net reclassification index of 9.9% in the overall population. Sex-specific analyses are presented in the manuscript. Conclusions: Adding plaque and CIMT to TRF improves CHD risk prediction in the ARIC (Atherosclerosis Risk In Communities) study. © 2010 American College of Cardiology Foundation.


Nambi V.,Baylor College of Medicine | Nambi V.,Center for Cardiovascular Disease Prevention | Chambless L.,University of North Carolina at Chapel Hill | He M.,University of North Carolina at Chapel Hill | And 5 more authors.
European Heart Journal | Year: 2012

Aims Carotid intimamedia thickness (CIMT) and plaque information can improve coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). However, obtaining adequate images of all carotid artery segments (A-CIMT) may be difficult. Of A-CIMT, the common carotid artery intimamedia thickness (CCA-IMT) is relatively more reliable and easier to measure. We evaluated whether CCA-IMT is comparable to A-CIMT when added to TRF and plaque information in improving CHD risk prediction in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results Ten-year CHD risk prediction models using TRF alone, TRF A-CIMT plaque, and TRF CCA-IMT plaque were developed for the overall cohort, men, and women. The area under the receiver operator characteristic curve (AUC), per cent individuals reclassified, net reclassification index (NRI), and model calibration by the GrønnesbyBorgan test were estimated. There were 1722 incident CHD events in 12 576 individuals over a mean follow-up of 15.2 years. The AUC for TRF only, TRF A-CIMT plaque, and TRF CCA-IMT plaque models were 0.741, 0.754, and 0.753, respectively. Although there was some discordance when the CCA-IMT plaque-and A-CIMT plaque-based risk estimation was compared, the NRI and clinical NRI (NRI in the intermediate-risk group) when comparing the CIMT models with TRF-only model, per cent reclassified, and test for model calibration were not significantly different. Conclusion Coronary heart disease risk prediction can be improved by adding A-CIMT plaque or CCA-IMT plaque information to TRF. Therefore, evaluating the carotid artery for plaque presence and measuring CCA-IMT, which is easier and more reliable than measuring A-CIMT, provide a good alternative to measuring A-CIMT for CHD risk prediction. © 2011 The Author.


Ballantyne C.M.,Baylor College of Medicine | Ballantyne C.M.,Center for Cardiovascular Disease Prevention | Davidson M.H.,University of Chicago | MacDougall D.E.,Esperion Therapeutics | And 5 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives The aim of this study was to assess the lipid-altering efficacy and safety of ETC-1002 in subjects with hypercholesterolemia. Background ETC-1002 is a small molecule that modulates pathways of cholesterol, fatty acid, and carbohydrate metabolism and may have therapeutic benefits in treating hypercholesterolemia and other cardiometabolic risk factors. Methods This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated patients (n = 177) with elevated low-density lipoprotein cholesterol (LDL-C) (130 to 220 mg/dl), who were stratified by baseline triglycerides (not elevated [<150 mg/dl] or elevated [150-<400 mg/dl]) and randomized to receive 40, 80, or 120 mg of ETC-1002 or placebo once daily for 12 weeks. Outcomes included changes in LDL-C (primary endpoint), other lipids, and cardiometabolic risk factors; and safety. Results ETC-1002 40, 80, and 120 mg lowered least-squares mean ± SE LDL-C levels by 17.9 ± 2.2%, 25.0 ± 2.1%, and 26.6 ± 2.2%, respectively, versus a reduction of 2.1 ± 2.2% with placebo (all, p < 0.0001); LDL-C lowering was similar between the subgroups with nonelevated and elevated triglycerides. ETC-1002 also lowered non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, and LDL particle number (all, p < 0.0001) in a dose-dependent manner; HDL-C and triglyceride levels were relatively unchanged. Post-hoc analyses suggest that ETC-1002 may have favorable effects on other cardiometabolic risk factors. The ETC-1002 and placebo groups did not demonstrate clinically meaningful differences in adverse events or other safety assessments. Conclusions ETC-1002 significantly lowered LDL-C levels up to 27% across a broad range of baseline triglycerides and was generally safe and well tolerated. ETC-1002 has a novel mechanism of action and may be useful for reducing LDL-C. (A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides; NCT01262638). © 2013 by the American College of Cardiology Foundation.


Efstathiou S.P.,Center for Cardiovascular Disease Prevention | Skeva I.I.,Center for Cardiovascular Disease Prevention | Zorbala E.,Center for Cardiovascular Disease Prevention | Georgiou E.,Center for Cardiovascular Disease Prevention | Mountokalakis T.D.,Center for Cardiovascular Disease Prevention
Circulation | Year: 2012

Background: There are well-established predisposing factors for the development of metabolic syndrome (MetS) in childhood or adolescence, but no specific risk profile has been identified as yet. The Prediction of Metabolic Syndrome in Adolescence (PREMA) study was conducted (1) to construct a classification score that could detect children at high risk for MetS in adolescence and (2) to test its predictive accuracy. Methods and Results: In the derivation cohort (1270 children), data from natal and parental profile and from initial laboratory assessment at 6 to 8 years of age were used to detect independent predictors of MetS at 13 to 15 years of age according to the International Diabetes Federation definition. In the validation cohort (1091 adolescents), the discriminatory capacity of the derived prediction score was tested on an independent adolescent population. MetS was diagnosed in 105 adolescents in the derivation phase (8%), whereas birth weight <10th percentile (odds ratio, 6.02; 95% confidence interval, 2.53-10.12, P<0.001), birth head circumference <10th percentile (odds ratio, 4.15; 95% confidence interval, 2.04-7.14, P<0.001), and parental overweight or obesity (in at least 1 parent; odds ratio, 3.22; 95% confidence interval, 1.30-5.29, P<0.01) were independently associated with diagnosis of MetS in adolescence. Among adolescents in the validation cohort (86 [8%] with MetS), the presence of all these 3 predictors predicted MetS with a sensitivity of 91% and a specificity of 98%. Conclusions: The coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be useful for detection of children at risk of developing MetS in adolescence. (Circulation. 2012;125:902-910.) © 2012 American Heart Association, Inc.


Mora S.,Center for Cardiovascular Disease Prevention | Mora S.,Harvard University | Glynn R.J.,Center for Cardiovascular Disease Prevention | Glynn R.J.,Harvard University | And 2 more authors.
Circulation | Year: 2013

BACKGROUND - : Chemically measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL measures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy. METHODS AND RESULTS - : In Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10 886 participants without cardiovascular disease (CVD) before and after random allocation to rosuvastatin 20 mg/d or placebo. Levels were examined with first CVD (n=234). HDL-P correlated better with apoA-I (Spearman r=0.69, P<0.0001) than with HDL-C (r=0.55, P<0.0001). Rosuvastatin lowered low-density lipoprotein cholesterol (49%) and raised HDL-C (6.1%), apoA-I (2.1%), HDL-P (3.8%), and HDL size (1.2%); all P<0.0001. Among placebo-allocated individuals, on-treatment HDL-C, apoA-I, and HDL-P had similar inverse associations with CVD (risk factor-adjusted hazard ratio and 95% confidence interval per 1 standard deviation: 0.79 [0.63-0.98], 0.75 [0.62-0.92], and 0.81 [0.67-0.97], respectively). Among rosuvastatin-allocated individuals, on-treatment HDL-P had a statistically significant and somewhat stronger association with CVD (0.73, 0.57-0.93, P=0.01) than HDL-C (0.82, 0.63-1.08, P=0.16) or apoA-I (0.86, 0.67-1.10, P=0.22). Among rosuvastatin-allocated individuals, on-treatment HDL-P remained significant (0.72, 0.53-0.97, P=0.03) after additionally adjusting for HDL-C. In risk factor-adjusted models, HDL size showed no significant association with CVD. CONCLUSIONS - : In the setting of potent statin therapy, HDL particle number may be a better marker of residual risk than chemically measured HDL-C or apoA-I. This has potential implications for evaluating novel therapies targeting HDL.


Negi S.I.,Baylor College of Medicine | Negi S.I.,Center for Cardiovascular Disease Prevention | Nambi V.,Baylor College of Medicine | Nambi V.,Center for Cardiovascular Disease Prevention
Current Atherosclerosis Reports | Year: 2012

Improving the 10-year coronary heart disease (CHD) risk prediction beyond its current state is important as the current risk prediction schemes classify the majority of individuals who experience an incident CHD event as low or intermediate in risk. B-mode ultrasound-based carotid intima-media thickness (CIMT) measurement and carotid plaque detection is one of the surrogate markers of atherosclerosis that has shown value in CHD risk prediction. It has been shown that adding either CIMT, plaque, or both to traditional risk prediction models improves CHD risk prediction. Carotid ultrasound-based CIMT measurement and plaque identification is noninvasive, safe, and relatively inexpensive. Recent guidelines have given CIMT and plaque-based risk prediction a class II A recommendation. This article reviews the available data related to the use of CIMT and plaque information in CHD risk prediction. © Springer Science+Business Media, LLC 2012.


Mora S.,Center for Cardiovascular Disease Prevention | Mora S.,Harvard University | Glynn R.J.,Center for Cardiovascular Disease Prevention | Glynn R.J.,Harvard University | And 5 more authors.
Circulation | Year: 2010

Background: Statin therapy in women without cardiovascular disease (CVD) is controversial, given the insufficient evidence of benefit. We analyzed sex-specific outcomes in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and synthesized the results with prior trials. Methods and results: JUPITER participants included 6801 women ≥60 years of age and 11 001 men ≥50 years of age with high-sensitivity C-reactive protein ≥2 mg/L and low-density lipoprotein cholesterol <130 mg/dL randomized to rosuvastatin versus placebo. Meta-analysis studies were randomized placebo-controlled statin trials with predominantly or exclusively primary prevention in women and sex-specific outcomes (20 147 women; >276 CVD events; mean age, 63 to 69 years). Absolute CVD rates (per 100 person-years) in JUPITER women for rosuvastatin and placebo (0.57 and 1.04, respectively) were lower than for men (0.88 and 1.54, respectively), with similar relative risk reduction in women (hazard ratio, 0.54; 95% confidence interval, 0.37 to 0.80; P=0.002) and men (hazard ratio, 0.58; 95% confidence interval, 0.45 to 0.73; P<0.001). In women, there was significant reduction in revascularization/unstable angina and nonsignificant reductions in other components of the primary end point. Meta-analysis of 13 154 women (240 CVD events; 216 total deaths) from exclusively primary prevention trials found a significant reduction in primary CVD events with statins by a third (relative risk, 0.63; 95% confidence interval, 0.49 to 0.82; P<0.001; P for heterogeneity=0.56) with a smaller nonsignificant effect on total mortality (relative risk, 0.78; 95% confidence interval, 0.53 to 1.15; P=0.21; P for heterogeneity=0.20). Similar results were obtained for trials that were predominantly but not exclusively primary prevention. Conclusion: JUPITER demonstrated that in primary prevention rosuvastatin reduced CVD events in women with a relative risk reduction similar to that in men, a finding supported by meta-analysis of primary prevention statin trials. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. Copyright © 2010 American Heart Association. All rights reserved.


News Article | November 28, 2016
Site: www.eurekalert.org

A new study looking at deaths from cancer, cardiovascular disease and all causes suggests that an inflammatory marker detected in blood tests in middle-aged adults can better predict the risk of death compared with another similar biomarker. The study is published in CMAJ (Canadian Medical Association Journal). These findings can be useful in the developing area of personalized medicine. "Omics technologies are exciting, as they allow the concurrent assessment of many biomarkers, some of which may turn out to be important to detect preclinical states of diseases or be markers of future disease," states Prof. Archana Singh-Manoux, Inserm (France) and University College London (UK). Inflammatory markers are known to be associated with cancer, chronic heart disease and other serious health conditions. However, the marker that is most useful in predicting these diseases continues to be debated. The authors looked at markers of inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP) and α1-acid glycoprotein (AGP); the latter was found in a recent metabolomics study to be a strong predictor of death within 5 years. The CMAJ study included data collected between 1997 and 1999 on 6545 men and women aged 45-69 years. Participants were followed to 2015 to determine if they had died. "When a recent metabolomics study highlighted the importance of AGP, our question was how relevant is this marker when compared to other known inflammatory markers. The novelty of our approach lies in being able to assess risk of mortality in the short- and long-term. Our findings show IL-6, which is already known to be important to heart disease, to do better than AGP." "Research on biomarkers is progressing fast, and it is important to undertake checks like in the one in our study, to shape future research on biomarkers," states Prof. Singh-Manoux. In a related commentary, Dr. Paul Ridker, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, writes, "biomarker discovery is crucial for thinking about new treatment targets. With regard to AGP, CRP and IL-6, what remains uncertain is whether reducing inflammation can reduce cardiovascular event rates."


News Article | November 29, 2016
Site: www.biosciencetechnology.com

A new study looking at deaths from cancer, cardiovascular disease and all causes suggests that an inflammatory marker detected in blood tests in middle-aged adults can better predict the risk of death compared with another similar biomarker. The study is published in CMAJ (Canadian Medical Association Journal). These findings can be useful in the developing area of personalized medicine. "Omics technologies are exciting, as they allow the concurrent assessment of many biomarkers, some of which may turn out to be important to detect preclinical states of diseases or be markers of future disease," states Prof. Archana Singh-Manoux, Inserm (France) and University College London (UK). Inflammatory markers are known to be associated with cancer, chronic heart disease and other serious health conditions. However, the marker that is most useful in predicting these diseases continues to be debated. The authors looked at markers of inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP) and α1-acid glycoprotein (AGP); the latter was found in a recent metabolomics study to be a strong predictor of death within 5 years. The CMAJ study included data collected between 1997 and 1999 on 6545 men and women aged 45-69 years. Participants were followed to 2015 to determine if they had died. "When a recent metabolomics study highlighted the importance of AGP, our question was how relevant is this marker when compared to other known inflammatory markers. The novelty of our approach lies in being able to assess risk of mortality in the short- and long-term. Our findings show IL-6, which is already known to be important to heart disease, to do better than AGP." "Research on biomarkers is progressing fast, and it is important to undertake checks like in the one in our study, to shape future research on biomarkers," states Prof. Singh-Manoux. In a related commentary, Dr. Paul Ridker, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, writes, "biomarker discovery is crucial for thinking about new treatment targets. With regard to AGP, CRP and IL-6, what remains uncertain is whether reducing inflammation can reduce cardiovascular event rates."

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