@article {1408, title = {Development and validation of a coronary risk prediction model for older U.S. and European persons in the Cardiovascular Health Study and the Rotterdam Study.}, journal = {Ann Intern Med}, volume = {157}, year = {2012}, month = {2012 Sep 18}, pages = {389-97}, abstract = {

BACKGROUND: Risk scores for prediction of coronary heart disease (CHD) in older adults are needed.

OBJECTIVE: To develop a sex-specific CHD risk prediction model for older adults that accounts for competing risks for death.

DESIGN: 2 observational cohort studies, using data from 4946 participants in the Cardiovascular Health Study (CHS) and 4303 participants in the Rotterdam Study (RS).

SETTING: Community settings in the United States (CHS) and Rotterdam, the Netherlands (RS).

PARTICIPANTS: Persons aged 65 years or older who were free of cardiovascular disease.

MEASUREMENTS: A composite of nonfatal myocardial infarction and coronary death.

RESULTS: During a median follow-up of 16.5 and 14.9 years, 1166 CHS and 698 RS participants had CHD events, respectively. Deaths from noncoronary causes largely exceeded the number of CHD events, complicating accurate CHD risk predictions. The prediction model had moderate ability to discriminate between events and nonevents (c-statistic, 0.63 in both U.S. and European men and 0.67 and 0.68 in U.S. and European women). The model was well-calibrated; predicted risks were in good agreement with observed risks. Compared with the Framingham point scores, the prediction model classified elderly U.S. persons into higher risk categories but elderly European persons into lower risk categories. Differences in classification accuracy were not consistent and depended on cohort and sex. Adding newer cardiovascular risk markers to the model did not substantially improve performance.

LIMITATION: The model may be less applicable in nonwhite populations, and the comparison Framingham model was not designed for adults older than 79 years.

CONCLUSION: A CHD risk prediction model that accounts for deaths from noncoronary causes among older adults provided well-calibrated risk estimates but was not substantially more accurate than Framingham point scores. Moreover, adding newer risk markers did not improve accuracy. These findings emphasize the difficulties of predicting CHD risk in elderly persons and the need to improve these predictions.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; The Netherlands Organisation for Scientific Research; and the Netherlands Organisation for Health Research and Development.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Cause of Death, Coronary Disease, European Continental Ancestry Group, Female, Humans, Incidence, Male, Models, Statistical, Multivariate Analysis, Netherlands, Prospective Studies, Risk Assessment, Risk Factors, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-157-6-201209180-00002}, author = {Koller, Michael T and Leening, Maarten J G and Wolbers, Marcel and Steyerberg, Ewout W and Hunink, M G Myriam and Schoop, Rotraut and Hofman, Albert and Bucher, Heiner C and Psaty, Bruce M and Lloyd-Jones, Donald M and Witteman, Jacqueline C M} } @article {6811, title = {Association of Cardiometabolic Multimorbidity With Mortality.}, journal = {JAMA}, volume = {314}, year = {2015}, month = {2015 Jul 7}, pages = {52-60}, abstract = {

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing.

OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.

DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates.

EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).

MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy.

RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95\% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95\% CI, 2.0-2.2) in those with stroke, 2.0 (95\% CI, 1.9-2.2) in those with MI, 3.7 (95\% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95\% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95\% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95\% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.

CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

}, keywords = {Adult, Aged, Comorbidity, Diabetes Mellitus, Female, Humans, Life Expectancy, Male, Middle Aged, Mortality, Myocardial Infarction, Risk Factors, Stroke}, issn = {1538-3598}, doi = {10.1001/jama.2015.7008}, author = {Di Angelantonio, Emanuele and Kaptoge, Stephen and Wormser, David and Willeit, Peter and Butterworth, Adam S and Bansal, Narinder and O{\textquoteright}Keeffe, Linda M and Gao, Pei and Wood, Angela M and Burgess, Stephen and Freitag, Daniel F and Pennells, Lisa and Peters, Sanne A and Hart, Carole L and H{\r a}heim, Lise Lund and Gillum, Richard F and Nordestgaard, B{\o}rge G and Psaty, Bruce M and Yeap, Bu B and Knuiman, Matthew W and Nietert, Paul J and Kauhanen, Jussi and Salonen, Jukka T and Kuller, Lewis H and Simons, Leon A and van der Schouw, Yvonne T and Barrett-Connor, Elizabeth and Selmer, Randi and Crespo, Carlos J and Rodriguez, Beatriz and Verschuren, W M Monique and Salomaa, Veikko and Sv{\"a}rdsudd, Kurt and van der Harst, Pim and Bj{\"o}rkelund, Cecilia and Wilhelmsen, Lars and Wallace, Robert B and Brenner, Hermann and Amouyel, Philippe and Barr, Elizabeth L M and Iso, Hiroyasu and Onat, Altan and Trevisan, Maurizio and D{\textquoteright}Agostino, Ralph B and Cooper, Cyrus and Kavousi, Maryam and Welin, Lennart and Roussel, Ronan and Hu, Frank B and Sato, Shinichi and Davidson, Karina W and Howard, Barbara V and Leening, Maarten J G and Leening, Maarten and Rosengren, Annika and D{\"o}rr, Marcus and Deeg, Dorly J H and Kiechl, Stefan and Stehouwer, Coen D A and Nissinen, Aulikki and Giampaoli, Simona and Donfrancesco, Chiara and Kromhout, Daan and Price, Jackie F and Peters, Annette and Meade, Tom W and Casiglia, Edoardo and Lawlor, Debbie A and Gallacher, John and Nagel, Dorothea and Franco, Oscar H and Assmann, Gerd and Dagenais, Gilles R and Jukema, J Wouter and Sundstr{\"o}m, Johan and Woodward, Mark and Brunner, Eric J and Khaw, Kay-Tee and Wareham, Nicholas J and Whitsel, Eric A and Nj{\o}lstad, Inger and Hedblad, Bo and Wassertheil-Smoller, Sylvia and Engstr{\"o}m, Gunnar and Rosamond, Wayne D and Selvin, Elizabeth and Sattar, Naveed and Thompson, Simon G and Danesh, John} } @article {7373, title = {Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function.}, journal = {J Clin Invest}, volume = {127}, year = {2017}, month = {2017 May 01}, pages = {1798-1812}, abstract = {

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.

METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.

RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.

CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.

FUNDING: For detailed information per study, see Acknowledgments.

}, issn = {1558-8238}, doi = {10.1172/JCI84840}, author = {Wild, Philipp S and Felix, Janine F and Schillert, Arne and Teumer, Alexander and Chen, Ming-Huei and Leening, Maarten J G and V{\"o}lker, Uwe and Gro{\ss}mann, Vera and Brody, Jennifer A and Irvin, Marguerite R and Shah, Sanjiv J and Pramana, Setia and Lieb, Wolfgang and Schmidt, Reinhold and Stanton, Alice V and Malzahn, D{\"o}rthe and Smith, Albert Vernon and Sundstr{\"o}m, Johan and Minelli, Cosetta and Ruggiero, Daniela and Lyytik{\"a}inen, Leo-Pekka and Tiller, Daniel and Smith, J Gustav and Monnereau, Claire and Di Tullio, Marco R and Musani, Solomon K and Morrison, Alanna C and Pers, Tune H and Morley, Michael and Kleber, Marcus E and Aragam, Jayashri and Benjamin, Emelia J and Bis, Joshua C and Bisping, Egbert and Broeckel, Ulrich and Cheng, Susan and Deckers, Jaap W and del Greco M, Fabiola and Edelmann, Frank and Fornage, Myriam and Franke, Lude and Friedrich, Nele and Harris, Tamara B and Hofer, Edith and Hofman, Albert and Huang, Jie and Hughes, Alun D and K{\"a}h{\"o}nen, Mika and Investigators, Knhi and Kruppa, Jochen and Lackner, Karl J and Lannfelt, Lars and Laskowski, Rafael and Launer, Lenore J and Leosdottir, Margr{\'e}t and Lin, Honghuang and Lindgren, Cecilia M and Loley, Christina and MacRae, Calum A and Mascalzoni, Deborah and Mayet, Jamil and Medenwald, Daniel and Morris, Andrew P and M{\"u}ller, Christian and M{\"u}ller-Nurasyid, Martina and Nappo, Stefania and Nilsson, Peter M and Nuding, Sebastian and Nutile, Teresa and Peters, Annette and Pfeufer, Arne and Pietzner, Diana and Pramstaller, Peter P and Raitakari, Olli T and Rice, Kenneth M and Rivadeneira, Fernando and Rotter, Jerome I and Ruohonen, Saku T and Sacco, Ralph L and Samdarshi, Tandaw E and Schmidt, Helena and Sharp, Andrew S P and Shields, Denis C and Sorice, Rossella and Sotoodehnia, Nona and Stricker, Bruno H and Surendran, Praveen and Thom, Simon and T{\"o}glhofer, Anna M and Uitterlinden, Andr{\'e} G and Wachter, Rolf and V{\"o}lzke, Henry and Ziegler, Andreas and M{\"u}nzel, Thomas and M{\"a}rz, Winfried and Cappola, Thomas P and Hirschhorn, Joel N and Mitchell, Gary F and Smith, Nicholas L and Fox, Ervin R and Dueker, Nicole D and Jaddoe, Vincent W V and Melander, Olle and Russ, Martin and Lehtim{\"a}ki, Terho and Ciullo, Marina and Hicks, Andrew A and Lind, Lars and Gudnason, Vilmundur and Pieske, Burkert and Barron, Anthony J and Zweiker, Robert and Schunkert, Heribert and Ingelsson, Erik and Liu, Kiang and Arnett, Donna K and Psaty, Bruce M and Blankenberg, Stefan and Larson, Martin G and Felix, Stephan B and Franco, Oscar H and Zeller, Tanja and Vasan, Ramachandran S and D{\"o}rr, Marcus} }