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Progression of valvular calcification and risk of incident stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

      Highlights

      • We examined valve calcium progression with stroke risk in a multiethnic cohort.
      • Progression of mitral annular calcium was associated with higher stroke risk.
      • This was independent of cardiovascular risk factors and coronary artery calcium.
      • However, progression of aortic valve calcium was not associated with stroke risk.

      Abstract

      Background and aims

      Prevalent valvular calcification (VC) is associated with stroke but little is known about associations of VC progression with stroke.

      Methods

      Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors.

      Results

      We studied 5,539 MESA participants free of baseline CVD and atrial fibrillation. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 83% had no progression of VC; 15%, progression at one site (AVC or MAC), and 3%, progression at both sites. Over a median of 12 years, 211 total and 167 ischemic strokes occurred. The number of sites with VC progression (range 0–2) was not associated with total and ischemic stroke (all p > 0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratio (95% CI) 1.59 (1.11, 2.28)] and ischemic stroke [1.64 (1.10, 2.45)]. Results remained significant after further adjustment for baseline coronary artery calcification. After excluding participants with interim atrial fibrillation and coronary heart disease, findings were no longer statistically significant in fully-adjusted models. There was no interaction by age, sex, or race/ethnicity. There was no association with AVC progression and stroke.

      Conclusions

      Progression of MAC but not AVC over 2.4 years is associated with increased risk of total and ischemic stroke.

      Graphical abstract

      Keywords

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      References

        • Benjamin E.J.
        • Muntner P.
        • Alonso A.
        • et al.
        Heart disease and stroke statistics-2019 update: a report from the American heart association.
        Circulation. 2019; 139: e56-e528
        • Ovbiagele B.
        • Nguyen-Huynh M.N.
        Stroke epidemiology: advancing our understanding of disease mechanism and therapy.
        Neurotherapeutics. 2011; 8: 319-329
        • Budoff M.J.
        • Young R.
        • Burke G.
        • et al.
        Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
        Eur. Heart J. 2018; 39: 2401-2408
        • Budoff M.J.
        • Nasir K.
        • Katz R.
        • et al.
        Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA).
        Atherosclerosis. 2011; 215: 196-202
        • Hermann D.M.
        • Lehmann N.
        • Gronewold J.
        • et al.
        Thoracic aortic calcification is associated with incident stroke in the general population in addition to established risk factors.
        Eur. Heart J. Cardiovasc. Imag. 2015; 16: 684-690
        • Fox C.S.
        • Vasan R.S.
        • Parise H.
        • et al.
        Mitral annular calcification predicts cardiovascular morbidity and mortality: the Framingham Heart Study.
        Circulation. 2003; 107: 1492-1496
        • Owens D.S.
        • Budoff M.J.
        • Katz R.
        • et al.
        Aortic valve calcium independently predicts coronary and cardiovascular events in a primary prevention population.
        JACC Cardiovasc. Imag. 2012; 5: 619-625
        • O'Neal W.T.
        • Efird J.T.
        • Nazarian S.
        • et al.
        Mitral annular calcification progression and the risk of atrial fibrillation: results from MESA.
        Eur. Heart J. Cardiovasc. Imag. 2018; 19: 279-284
        • Kim J.
        • Budoff M.J.
        • Nasir K.
        • et al.
        Thoracic aortic calcium, cardiovascular disease events, and all-cause mortality in asymptomatic individuals with zero coronary calcium: the Multi-Ethnic Study of Atherosclerosis (MESA).
        Atherosclerosis. 2017; 257: 1-8
        • Tison G.H.
        • Guo M.
        • Blaha M.J.
        • et al.
        Multisite extracoronary calcification indicates increased risk of coronary heart disease and all-cause mortality: the Multi-Ethnic Study of Atherosclerosis.
        J. Cardiovasc. Comput. Tomogr. 2015; 9: 406-414
        • Kianoush S.
        • Al Rifai M.
        • Cainzos-Achirica M.
        • et al.
        Thoracic extra-coronary calcification for the prediction of stroke: the Multi-Ethnic Study of Atherosclerosis.
        Atherosclerosis. 2017; 267: 61-67
        • Kizer J.R.
        • Wiebers D.O.
        • Whisnant J.P.
        • et al.
        Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study.
        Stroke. 2005; 36: 2533-2537
        • Benjamin E.J.
        • Plehn J.F.
        • D'Agostino R.B.
        • et al.
        Mitral annular calcification and the risk of stroke in an elderly cohort.
        N. Engl. J. Med. 1992; 327: 374-379
        • Wexler L.
        • Brundage B.
        • Crouse J.
        • et al.
        Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications.
        Circulation. 1996; 94: 1175-1192
        • 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
        • Levey A.S.
        • Stevens L.A.
        Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions.
        Am. J. Kidney Dis. 2010; 55: 622-627
        • Carr J.J.
        • Nelson J.C.
        • Wong N.D.
        • et al.
        Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of multi-ethnic study of atherosclerosis (MESA) and coronary artery risk development in young adults (CARDIA) study.
        Radiology. 2005; 234: 35-43
        • Ezeigwe A.
        • Fashanu O.E.
        • Zhao D.
        • et al.
        The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: the Multi-Ethnic Study of Atherosclerosis.
        Atherosclerosis. 2019; 282: 91-99
        • Agatston A.S.
        • Janowitz W.R.
        • Hildner F.J.
        • et al.
        Quantification of coronary artery calcium using ultrafast computed tomography.
        J. Am. Coll. Cardiol. 1990; 15: 827-832
        • Budoff M.J.
        • Katz R.
        • Wong N.D.
        • et al.
        Effect of scanner type on the reproducibility of extracoronary measures of calcification: the multi-ethnic study of atherosclerosis.
        Acad. Radiol. 2007; 14: 1043-1049
        • Budoff M.J.
        • Takasu J.
        • Katz R.
        • et al.
        Reproducibility of CT measurements of aortic valve calcification, mitral annulus calcification, and aortic wall calcification in the multi-ethnic study of atherosclerosis.
        Acad. Radiol. 2006; 13: 166-172
        • Longstreth Jr., W.T.
        • Gasca N.C.
        • Gottesman R.F.
        • et al.
        Adjudication of transient ischemic attack and stroke in the multi-ethnic study of atherosclerosis.
        Neuroepidemiology. 2018; 50: 23-28
        • Detrano R.
        • Guerci A.D.
        • Carr J.J.
        • et al.
        Coronary calcium as a predictor of coronary events in four racial or ethnic groups.
        N. Engl. J. Med. 2008; 358: 1336-1345
        • Heckbert S.R.
        • Wiggins K.L.
        • Blackshear C.
        • et al.
        Pericardial fat volume and incident atrial fibrillation in the multi-ethnic study of atherosclerosis and Jackson heart study.
        Obesity. 2017; 25: 1115-1121
        • Kanjanauthai S.
        • Nasir K.
        • Katz R.
        • et al.
        Relationships of mitral annular calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA).
        Atherosclerosis. 2010; 213: 558-562