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2.  Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque 
Bis, Joshua C. | Kavousi, Maryam | Franceschini, Nora | Isaacs, Aaron | Abecasis, Gonçalo R | Schminke, Ulf | Post, Wendy | Smith, Albert V. | Cupples, L. Adrienne | Markus, Hugh S | Schmidt, Reinhold | Huffman, Jennifer E. | Lehtimäki, Terho | Baumert, Jens | Münzel, Thomas | Heckbert, Susan R. | Dehghan, Abbas | North, Kari | Oostra, Ben | Bevan, Steve | Stoegerer, Eva-Maria | Hayward, Caroline | Raitakari, Olli | Meisinger, Christa | Schillert, Arne | Sanna, Serena | Völzke, Henry | Cheng, Yu-Ching | Thorsson, Bolli | Fox, Caroline S. | Rice, Kenneth | Rivadeneira, Fernando | Nambi, Vijay | Halperin, Eran | Petrovic, Katja E. | Peltonen, Leena | Wichmann, H. Erich | Schnabel, Renate B. | Dörr, Marcus | Parsa, Afshin | Aspelund, Thor | Demissie, Serkalem | Kathiresan, Sekar | Reilly, Muredach P. | Uitterlinden, Andre | Couper, David J. | Sitzer, Matthias | Kähönen, Mika | Illig, Thomas | Wild, Philipp S. | Orru, Marco | Lüdemann, Jan | Shuldiner, Alan R. | Eiriksdottir, Gudny | White, Charles C. | Rotter, Jerome I. | Hofman, Albert | Seissler, Jochen | Zeller, Tanja | Usala, Gianluca | Ernst, Florian | Launer, Lenore J. | D'Agostino, Ralph B. | O'Leary, Daniel H. | Ballantyne, Christie | Thiery, Joachim | Ziegler, Andreas | Lakatta, Edward G. | Chilukoti, Ravi Kumar | Harris, Tamara B. | Wolf, Philip A. | Psaty, Bruce M. | Polak, Joseph F | Li, Xia | Rathmann, Wolfgang | Uda, Manuela | Boerwinkle, Eric | Klopp, Norman | Schmidt, Helena | Wilson, James F | Viikari, Jorma | Koenig, Wolfgang | Blankenberg, Stefan | Newman, Anne B. | Witteman, Jacqueline | Heiss, Gerardo | van Duijn, Cornelia | Scuteri, Angelo | Homuth, Georg | Mitchell, Braxton D. | Gudnason, Vilmundur | O’Donnell, Christopher J.
Nature Genetics  2011;43(10):940-947.
doi:10.1038/ng.920
PMCID: PMC3257519  PMID: 21909108
genome-wide association study; genetic epidemiology; genetics; subclinical atherosclerosis; carotid intima media thickness; cardiovascular disease; cohort study; meta-analysis; risk
3.  Carotid-Wall Intima–Media Thickness and Cardiovascular Events 
The New England journal of medicine  2011;365(3):213-221.
BACKGROUND
Intima–media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.
METHODS
We measured the mean intima–media thickness of the common carotid artery and the maximum intima–media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima–media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima–media thickness values.
RESULTS
A total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima–media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima–media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima–media thickness of the internal carotid artery (7.6%, P<0.001) but not intima–media thickness of the common carotid artery (0.0%, P = 0.99). With the presence of plaque, defined as intima–media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P = 0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).
CONCLUSIONS
The maximum internal and mean common carotid-artery intima–media thicknesses both predict cardiovascular outcomes, but only the maximum intima–media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.)
doi:10.1056/NEJMoa1012592
PMCID: PMC3153949  PMID: 21774709
4.  Prevalence and Correlates of Silent Cerebral Infarcts in the Framingham Offspring Study 
Background and Purpose
Prior estimates of the prevalence of silent cerebral infarction (SCI) on magnetic resonance imaging (MRI) in community-based samples have varied between 5.8 and 17.7% depending on age, ethnicity, presence of co-morbidities and imaging techniques. We document the prevalence and risk factors associated with SCI at midlife in the community-based Framingham sample.
Methods
2040 Framingham Offspring (53% F; mean age 62±9 yrs) who attended the 6th examination (1996–98), underwent volumetric brain MRI (1999–2005) and were free of clinical stroke at MRI, constituted our study sample. We examined the age- and sex-specific prevalence and the clinical correlates of SCI using multivariable logistic regression models.
Results
At least one SCI was present in 10.7% of participants. 84% had a single lesion. SCI were largely located in the basal ganglia (52%), other subcortical (35%) and cortical areas (11%). Prevalent SCI was associated with the Framingham Stroke Risk Profile score (OR: 1.27; 95% CI: 1.10 – 1.46); Stage I hypertension by JNC-VII criteria (OR:1.56; CI:1.15 – 2.11)), an elevated plasma homocysteine in the highest quartile (OR: 2.23; CI: 1.42 – 3.51), atrial fibrillation (OR: 2.16; CI: 1.07 – 4.40), carotid stenosis >25% (OR: 1.62; 1.13 – 2.34)) and increased carotid intimal-medial thickness above the lowest quintile (OR: 1.65; CI: 1.22 – 2.24).
Conclusion
The prevalence and distribution of SCI in the Framingham Offspring.is comparable to prior estimates. Risk factors previously associated with clinical stroke were also found to be associated with midlife SCI. Our results support current guidelines emphasizing early detection and treatment of stroke risk factors.
doi:10.1161/STROKEAHA.108.516575
PMCID: PMC2712254  PMID: 18583555
cerebral infarction; magnetic resonance imaging; risk factors; prevalence; hypertension

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