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1.  Risk Factors Associated with the Incidence and Progression of Mitral Annulus Calcification: The Multi-Ethnic Study of Atherosclerosis 
American heart journal  2013;166(5):904-912.
Background
Significant cardiovascular morbidity has been associated with mitral annulus calcification (MAC), but limited data exist regarding its progression. The purpose of this study was to examine the natural history of and risk factors for MAC progression.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal cohort study of participants aged 45–84 years without clinical cardiovascular disease who underwent serial cardiac computed tomography studies with quantification of MAC. Regression models were used to identify risk factors associated with MAC incidence and progression.
Results
Prevalent MAC was observed in 534 of 5,895 (9%) participants. Over a median 2.3 years, 280 (5%) developed incident MAC. After adjustment, age was the strongest predictor of incident MAC (adjusted OR, 2.25 per 10 yrs; 95% CI, 1.97 to 2.58; P<0.0001). Female gender, white ethnicity, body mass index, diabetes, hypertension, hyperlipidemia, serum cholesterol, smoking, and interleukin-6 were also significant predictors of incident MAC. In participants with prevalent MAC, the median rate of change was 10.1 [IQR, −6.7, 60.7] Agatston units (AU)/year. Baseline MAC severity was the predominant predictor of rate of MAC progression (β-coefficient per 10 AU, 0.88; 95% CI, 0.85 to 0.91; P<0.0001), although ethnicity and smoking status possessed modest influence.
Conclusions
Several cardiovascular risk factors predicted incident MAC, as did female gender. Severity of baseline MAC was the primary predictor of MAC progression, suggesting that, while atherosclerotic processes may initiate MAC, they are only modestly associated with its progression over these time frames.
doi:10.1016/j.ahj.2013.08.015
PMCID: PMC3978772  PMID: 24176447
calcification; mitral valve; progression; risk factors; gender
2.  Associations of Left Ventricular Hypertrophy with Prevalent and Incident Valve Calcification: The Multi-Ethnic Study of Atherosclerosis 
JACC. Cardiovascular imaging  2012;5(8):781-788.
Objectives
We aim to evaluate the relationship between percent of predicted left ventricular mass (%PredLVM) and valve calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).
Background
Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood.
Methods
MESA is a longitudinal cohort study of men and women aged 45-84 years without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling.
Results
Prevalent AVC was observed in 630 and MAC in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, gender, body mass index, ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (OR=1.18 per SD increase in %PredLVM [95%CI 1.08 – 1.30]; p=0.0004) and MAC (OR=1.18 [95%CI 1.06 – 1.32]; p=0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95%CI 0.15 – 0.38]; p<0.0001) and MAC (risk difference = 0.20 [95%CI 0.03 – 0.37]; p=0.02). During follow-up (mean 2.4±0.9 years), 153 subjects (4%) developed AVC and 198 (5%) MAC. %PredLVM was associated with incident AVC (OR=1.24 [95%CI 1.04 – 1.47]; p=0.02) and MAC (OR=1.18 [1.01-1.40]; p=0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification.
Conclusions
Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders.
doi:10.1016/j.jcmg.2011.12.025
PMCID: PMC3426868  PMID: 22897991
aortic valve; calcification; left ventricular mass; mitral valve annulus
3.  Bisphosphonate use and the Prevalence of Valvular and Vascular Calcification in Women: The Multi-Ethnic Study of Atherosclerosis 
Objectives
To determine whether nitrogen-containing bisphosphonate (NCBP) therapy is associated with the prevalence of cardiovascular calcification.
Background
Cardiovascular calcification correlates with atherosclerotic disease burden. Experimental data suggest that NCBP may limit cardiovascular calcification, which has implications for disease prevention.
Methods
The relationship of NCBP use to the prevalence of aortic valve, aortic valve ring, mitral annulus, thoracic aorta, and coronary artery calcification (AVC, AVRC, MAC, TAC, and CAC, respectively) detected by computed tomography was assessed in 3,636 women within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling.
Results
Analyses were age-stratified because of a significant interaction between age and NCBP use (interaction p-values: AVC p<0.0001; AVRC p<0.0001; MAC p=0.002; TAC p<0.0001; CAC p=0.046). After adjusting for age, body mass index, demographics, diabetes, smoking, blood pressure, cholesterol levels, and statin, hormone replacement, and renin-angiotensin inhibitor therapy, NCBP use was associated with a lower prevalence of cardiovascular calcification in women ≥65 years old (prevalence ratio [95% confidence interval]: AVC 0.68 [0.41, 1.13]; AVRC 0.65 [0.51, 0.84]; MAC 0.54 [0.33, 0.93]; TAC 0.69 [0.54, 0.88]; CAC 0.89 [0.78, 1.02]), whereas calcification was more prevalent in NCBP users among the 2,181 women <65 years old (AVC 4.00 [2.33, 6.89]; AVRC 1.92 [1.42, 2.61]; MAC 2.35 [1.12, 4.84]; TAC 2.17 [1.49, 3.15]; CAC 1.23 [0.97, 1.57]).
Conclusions
Among women in the diverse MESA cohort, NCBPs were associated with decreased prevalence of cardiovascular calcification in older subjects, but more prevalent cardiovascular calcification in younger ones. Further study is warranted to clarify these age-dependent NCBP effects.
doi:10.1016/j.jacc.2010.05.050
PMCID: PMC3004769  PMID: 21070928
bisphosphonate; calcification; coronary artery; valve; vascular

Results 1-3 (3)