The 222 participants had a mean ± SD global resting MBF of 1.01 ± 0.23 ml/g/min (range 0.54 to 1.82 ml/g/min). During hyperemia, MBF increased significantly to 3.02 ± 0.84 ml/g/min (range 0.98 to 5.63 ml/g/min). Calculated as the ratio of hyperemic MBF divided by resting MBF, perfusion reserve averaged 3.05 ± 0.84 (range 1.18 to 5.24). The correlation between MBF and rate-pressure product was stronger at rest (Pearson r = 0.57) than during hyperemia (Pearson r = 0.28). Mean resting MBF, hyperemic MBF, and perfusion reserve were all significantly lower in men (0.93 ml/min/g, 2.66 ml/min/g, and 2.94, respectively) than in women (1.12 ml/min/g, 3.48 ml/min/g, and 3.20, respectively). Hyperemic MBF and perfusion reserve were also significantly lower in older subjects age 65 to 84 years (2.78 ml/min/g and 2.76, respectively) than in middle-age subjects age 45 to 64 years (3.14 ml/min/g and 3.20, respectively). None of the major perfusion measurements differed by ethnicity. The predicted 10-year CHD risk, estimated by risk factors using Framingham prediction equations, correlated inversely with hyperemic MBF (Pearson r = −0.46, p < 0.0001) and perfusion reserve (Pearson r = −0.33, p < 0.0001).
The CAC scores in these asymptomatic participants ranged from 0 to 6,063. Of 222 subjects, 103 subjects (46%) had a CAC score of 0, 59 (27%) had a CAC score of 0.1 to 99.9, 33 (15%) had a CAC score of 100 to 399, and 27 (12%) had a CAC score ≥400. The median of CAC scores for those with a score >0 was 102. Compared with those subjects with no evidence of CAC, those with CAC were significantly older and were more likely to be male (). The CAC score was also associated positively with most major CHD risk factors (data not shown) and the predicted 10-year CHD risk (Spearman r = 0.14, p = 0.04). The proportion of Hispanic subjects was similar across different CAC scores.
Demographic Characteristics and Myocardial Perfusion Measures Across Levels of Coronary Artery Calcification in Subjects With No Clinical Coronary Heart Disease (CHD) From the Multi-Ethnic Study of Atherosclerosis
Mean resting MBF did not differ across CAC levels (). In contrast, mean hyperemic MBF (3.31, 2.95, 2.65, and 2.53 ml/min/g) and perfusion reserve (3.34, 2.88, 2.82, and 2.60) were progressively lower across increasing CAC levels. The Spearman correlations of resting MBF, hyperemic MBF, and perfusion reserve with CAC scores were −0.03 (p = 0.70), −0.38 (p < 0.0001), and −0.35 (p < 0.0001), respectively. Consistent with the responses of MBF to the infusion of adenosine, the corresponding systemic hemodynamic responses, presented as the ratio of rate-pressure product at hyperemia to rest, was blunted in participants with elevated CAC scores. The inverse associations of hyperemic MBF and perfusion reserve with CAC score were similar in men and in women (p for interaction = 0.62 for hyperemic MBF, 0.69 for perfusion reserve), but were stronger in middle-age subjects than in older subjects (p for interaction = 0.03 for hyperemic MBF, 0.0004 for perfusion reserve) (). In the middle-age subjects, mean perfusion reserve was significantly lower in those with high CAC scores compared with those with no CAC. Correspondingly, the prevalence of reduced perfusion reserve (<2.5) was substantially higher across increasing levels of CAC score among middle-age participants (). A perfusion reserve lower than 2.5 was observed in only 12% of middle-age subjects with a CAC score of 0 but in nearly 80% of middle-age subjects with CAC score ≥400. By contrast, the prevalence of reduced perfusion reserve was only slightly higher among older subjects with a CAC score ≥100, compared with those with no CAC or a CAC score <100. Although presented as middle-age subjects compared with older subjects, attenuation of the inverse associations with advancing age was statistically significant throughout the age range of our study sample when age was modeled as a continuous variable.
Mean Myocardial Perfusion Measures Across Levels of Coronary Artery Calcification in Subjects With No Clinical Coronary Heart Disease, Stratified By Age and Gender From the Multi-Ethnic Study of Atherosclerosis
Figure 2 Prevalence of reduced perfusion reserve (<2.5) across levels of coronary artery calcification in subjects with no clinical coronary heart disease, stratified by age group. Numbers in bars are the number of subjects with reduced perfusion reserve/total (more ...)
A high CAC score remained significantly associated with a higher likelihood of reduced perfusion reserve after adjusting for age and gender (). Compared with subjects with a CAC score of 0, the age- and gender-adjusted odds ratios of reduced perfusion reserve were 2.16 (95% CI 0.96 to 4.84), 2.81 (95% CI 1.04 to 7.58), and 4.99 (95% CI 1.73 to 14.4) for those with a CAC score of 0.1 to 99.9, 100 to 399, and ≥400, respectively. Further adjustment for overall coronary risk factor burden, estimated using Framingham prediction equations, did not materially attenuate the association. The association between CAC scores and odds of reduced perfusion reserve was stronger in middle-age subjects than in older subjects (p for interaction = 0.03). Similar to that observed in a linear regression model, the attenuation of association with advancing age was also statistically significant when age was modeled as a continuous variable. Using low hyperemic MBF (<2.53 ml/min/g, which is the 40th percentile) alternatively as the response variable, with adjustment for resting MBF as an independent covariate, yielded somewhat weaker results (data not shown).
Odds Ratios (OR) and 95% Confidence Intervals (CI) of Reduced Perfusion Reserve (<2.5) Across Levels of Coronary Artery Calcification in Subjects With No Clinical Coronary Heart Disease From the Multi-Ethnic Study of Atherosclerosis
The CAC scores were calculated for specific coronary arteries—left main, left anterior descending, left circumflex, and right coronary artery—in 207 subjects; 31 (14%) subjects had CAC in 1 artery, 32 (15%) in 2 arteries, 33 (15%) in 3 arteries, and 10 (5%) in all 4 major arteries. Global hyperemic MBF and perfusion reserve were lower, with more arteries containing calcium (). The inverse association between perfusion reserve and number of arteries with calcium was similar in men and women (p for interaction = 0.81), but stronger in middle-age subjects than in older subjects (p for interaction = 0.008). The regional hyperemic MBF and perfusion reserve in the anterior segment of left ventricle myocardium, which is supplied by the left anterior descending artery, were inversely associated with CAC score in the left anterior descending artery (data not shown), similar to the inverse relationship observed between global MBF and total CAC scores. Region-specific associations could not be investigated in other artery territories because information about the left/right dominance of the coronary artery system was unavailable for MESA participants.
Table 4 Mean Myocardial Perfusion Measures Across Number of Coronary Arteries Containing Calcium (Coronary Artery Calcium Score >0 in the Respective Artery) in Subjects With No Clinical Coronary Heart Disease From The Multi-Ethnic Study of Atherosclerosis (more ...)