Mayo Clinic Proceedings Home

Basic vs More Complex Definitions of Family History in the Prediction of Coronary Heart Disease: The Multi-Ethnic Study of Atherosclerosis



      To determine whether family history of coronary heart disease (FH) definitions differ in their association with atherosclerotic cardiovascular disease (ASCVD) events.

      Patients and Methods

      Participants who provided FH data from July 17, 2000, through February 24, 2004, were identified. Definitions of FH were any, premature, and Familial Risk Assessment (FRA). Outcomes included coronary heart disease (CHD), stroke, peripheral artery disease, angina, and congestive heart failure. Multivariable-adjusted Cox models examined the association of FH definitions with events. C statistics and the net reclassification index examined the incremental prognostic contribution of each definition.


      In 6200 participants, the proportions of any FH and premature FH were 36% and 16%, respectively, and of weak, moderate, and strong familial risk were 20%, 16%, and 20%, respectively. Over median follow-up of 10.1 years (range, 0.02-11.5 years), 741 participants experienced a composite event. Compared with no FH, any FH was associated with incident CHD, angina, and composite ASCVD (hazard ratios [95% CIs]: 1.4 [1.1-1.8], 1.6 [1.2-2.1], and 1.3 [1.1-1.5], respectively). Similar results were obtained for premature FH compared with no FH and for strong compared with weak FRA for these 3 outcomes. There was no association between the FH definitions and noncoronary cardiovascular events. Compared with traditional risk factors (C statistic = 0.740), any FH, premature FH, and FRA all improved discrimination of composite ASCVD (all P < .01); however, the differences in C statistics among any FH (0.743), premature FH (0.742), and FRA (0.744) were numerically small, as were differences in the net reclassification index.


      A single question regarding the presence of FH in any first-degree relative performs just as well as more complicated assessments in predicting CHD.

      Trial Registration

      Abbreviations and Acronyms:

      ASCVD (atherosclerotic cardiovascular disease), BMI (body mass index), BP (blood pressure), CHD (coronary heart disease), CHF (congestive heart failure), DM (diabetes mellitus), FH (family history of coronary heart disease), FRA (Familial Risk Assessment), FRS (Framingham risk score), HDL-C (high-density lipoprotein cholesterol), IR (incident event rate), LDL-C (low-density lipoprotein cholesterol), MESA (Multi-Ethnic Study of Atherosclerosis), NRI (net reclassification index), PAD (peripheral artery disease), PCE (pooled cohort equations)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Safarova M.S.
        • Bailey K.R.
        • Kullo I.J.
        Association of a family history of coronary heart disease with initiation of statin therapy in individuals at intermediate rIsk: post hoc analysis of a randomized clinical trial.
        JAMA Cardiol. 2016; 1: 364-366
        • Goff Jr., D.C.
        • Lloyd-Jones D.M.
        • Bennett G.
        • et al.
        American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 63: 2935-2959
        • Dhiman P.
        • Kai J.
        • Horsfall L.
        • et al.
        Availability and quality of coronary heart disease family history in primary care medical records: implications for cardiovascular risk assessment.
        PLoS One. 2015; 9: e81998
        • Sesso H.D.
        • Lee I.M.
        • Gaziano J.M.
        • et al.
        Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women.
        Circulation. 2001; 104: 393-398
        • Lloyd-Jones D.M.
        • Nam B.H.
        • D'Agostino Sr., R.B.
        • et al.
        Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring.
        JAMA. 2004; 291: 2204-2211
        • Chow C.K.
        • Islam S.
        • Bautista L.
        • et al.
        Parental history and myocardial infarction risk across the world: the INTERHEART Study.
        J Am Coll Cardiol. 2011; 57: 619-627
        • Sivapalaratnam S.
        • Boekholdt S.M.
        • Trip M.D.
        • et al.
        Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study.
        Heart. 2010; 96: 1985-1989
        • Bachmann J.M.
        • Willis B.L.
        • Ayers C.R.
        • et al.
        Association between family history and coronary heart disease death across long-term follow-up in men: the Cooper Center Longitudinal Study.
        Circulation. 2012; 125: 3092-3098
        • Li R.
        • Bensen J.T.
        • Hutchinson R.G.
        • et al.
        Family risk score of coronary heart disease (CHD) as a predictor of CHD: the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI family heart study.
        Genet Epidemiol. 2000; 18: 236-250
        • Murabito J.M.
        • Pencina M.J.
        • Nam B.H.
        • et al.
        Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults.
        JAMA. 2005; 294: 3117-3123
        • Leander K.
        • Hallqvist J.
        • Reuterwall C.
        • Ahlbom A.
        • de Faire U.
        Family history of coronary heart disease, a strong risk factor for myocardial infarction interacting with other cardiovascular risk factors: results from the Stockholm Heart Epidemiology Program (SHEEP).
        Epidemiology. 2001; 12: 215-221
        • Jousilahti P.
        • Puska P.
        • Vartiainen E.
        • Pekkanen J.
        • Tuomilehto J.
        Parental history of premature coronary heart disease: an independent risk factor of myocardial infarction.
        J Clin Epidemiol. 1996; 49: 497-503
        • Friedlander Y.
        • Kark J.D.
        • Stein Y.
        Family history of myocardial infarction as an independent risk factor for coronary heart disease.
        Br Heart J. 1985; 53: 382-387
        • Yeboah J.
        • Young R.
        • McClelland R.L.
        • et al.
        Utility of nontraditional risk markers in atherosclerotic cardiovascular disease risk assessment.
        J Am Coll Cardiol. 2016; 67: 139-147
        • D'Agostino Sr., R.B.
        • Grundy S.
        • Sullivan L.M.
        • Wilson P.
        CHD Risk Prediction Group. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.
        JAMA. 2001; 286: 180-187
        • Bild D.E.
        • Bluemke D.A.
        • Burke G.L.
        • et al.
        Multi-ethnic study of atherosclerosis: objectives and design.
        Am J Epidemiol. 2002; 156: 871-881
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
        • American Diabetes Association
        Diagnosis and classification of diabetes mellitus.
        Diabetes Care. 2006; 29: S43-S48
        • Joint National Committee
        The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
        Arch Intern Med. 1997; 157: 2413-2446
        • Scheuner M.T.
        • Whitworth W.C.
        • McGruder H.
        • Yoon P.W.
        • Khoury M.J.
        Familial risk assessment for early-onset coronary heart disease.
        Genet Med. 2006; 8: 525-531
        • Scheuner M.T.
        • Setodji C.M.
        • Pankow J.S.
        • Blumenthal R.S.
        • Keeler E.
        General Cardiovascular Risk Profile identifies advanced coronary artery calcium and is improved by family history: the multiethnic study of atherosclerosis.
        Circ Cardiovasc Genet. 2010; 3: 97-105
        • Yeboah J.
        • Folsom A.R.
        • Burke G.L.
        • et al.
        Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis.
        Circulation. 2009; 120: 502-509
        • Budoff M.J.
        • McClelland R.L.
        • Nasir K.
        • et al.
        Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA).
        Am Heart J. 2009; 158: 554-561
        • Coylewright M.
        • Rice K.
        • Budoff M.J.
        • et al.
        Differentiation of severe coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.
        Atherosclerosis. 2011; 219: 616-622
        • Criqui M.H.
        • McClelland R.L.
        • McDermott M.M.
        • et al.
        The ankle-brachial index and incident cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis).
        J Am Coll Cardiol. 2010; 56: 1506-1512
        • Bahrami H.
        • Kronmal R.
        • Bluemke D.A.
        • et al.
        Differences in the incidence of congestive heart failure by ethnicity: the multi-ethnic study of atherosclerosis.
        Arch Intern Med. 2008; 168: 2138-2145
        • Yeboah J.
        • McClelland R.L.
        • Polonsky T.S.
        • et al.
        Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals.
        JAMA. 2012; 308: 788-795
        • Hunt S.C.
        • Williams R.R.
        • Barlow G.K.
        A comparison of positive family history definitions for defining risk of future disease.
        J Chronic Dis. 1986; 39: 809-821
        • Silberberg J.S.
        • Wlodarczyk J.
        • Fryer J.
        • Robertson R.
        • Hensley M.J.
        Risk associated with various definitions of family history of coronary heart disease: the Newcastle Family History Study II.
        Am J Epidemiol. 1998; 147: 1133-1139
        • Scheuner M.T.
        • Whitworth W.C.
        • McGruder H.
        • Yoon P.W.
        • Khoury M.J.
        Expanding the definition of a positive family history for early-onset coronary heart disease.
        Genet Med. 2006; 8: 491-501
        • Eaton C.B.
        • Bostom A.G.
        • Yanek L.
        • et al.
        Family history and premature coronary heart disease.
        J Am Board Fam Pract. 1996; 9: 312-318
        • Song J.W.
        • Chung K.C.
        Observational studies: cohort and case-control studies.
        Plast Reconstr Surg. 2010; 126: 2234-2242
        • O'Donnell C.J.
        Family history, subclinical atherosclerosis, and coronary heart disease risk: barriers and opportunities for the use of family history information in risk prediction and prevention.
        Circulation. 2004; 110: 2074-2076
        • Hippe M.
        • Vestbo J.
        • Bjerg A.M.
        • et al.
        Cardiovascular risk factor profile in subjects with familial predisposition to myocardial infarction in Denmark.
        J Epidemiol Community Health. 1997; 51: 266-271
        • Yusuf S.
        • Hawken S.
        • Ounpuu S.
        • et al.
        • INTERHEART Study Investigators
        Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
        Lancet. 2004; 364: 937-952
        • Piepoli M.F.
        • Hoes A.W.
        • Agewall S.
        • et al.
        • Authors/Task Force Members
        2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
        Eur Heart J. 2016; 37: 2315-2381
        • Rose G.
        Sick individuals and sick populations.
        Int J Epidemiol. 2001; 30: 427-432
        • Yoon P.W.
        • Scheuner M.T.
        • Jorgensen C.
        • Khoury M.J.
        Developing Family Healthware, a family history screening tool to prevent common chronic diseases.
        Prev Chronic Dis. 2009; 6: A33
        • Hecht H.
        • Blaha M.J.
        • Berman D.S.
        • et al.
        Clinical indications for coronary artery calcium scoring in asymptomatic patients: expert consensus statement from the Society of Cardiovascular Computed Tomography.
        J Cardiovasc Comput Tomogr. 2017; 1: 157-168
        • Khoury M.J.
        • Flanders W.D.
        Bias in using family history as a risk factor in case-control studies of disease.
        Epidemiology. 1995; 6: 511-519
        • Patel J.
        • Al Rifai M.
        • Blaha M.J.
        • et al.
        Coronary artery calcium improves risk assessment in adults with a family history of premature coronary heart disease: results from Multiethnic Study of Atherosclerosis.
        Circ Cardiovasc Imaging. 2015; 8: e003186
        • Mohler III, E.R.
        Peripheral arterial disease: identification and implications.
        Arch Intern Med. 2003; 163: 2306-2314