Canadian Neighbor Pharmacy: Results of Enhanced Coronary Calcification Determined by Electron Beam CT Is Strongly Related to Endothelial Dysfunction

Oct-30-2015

Endothelium-dependent FMDA total of 124 patients were enrolled (78 men; 63%; mean age, 67 ± 1 years); of these, 98 patients (79%) had positive EBCT results, ie, a CCS > 0. All patients were classified into three groups according to CCSs: group 1, no calcification (CCS 0) [n = 26]; group 2, small-to-moderate coronary calcification (CCS 1 to 199) [n = 50]; and group 3, moderate-to-severe calcification (CCS a 200) [n = 48]. The baseline characteristics of the three groups are shown in Table 1. In group 3, the patients were older than those in groups 1 and 2 (p < 0.05). No significant differences in baseline characteristics were found among the three groups, except there were more patients with hypertension and diabetes in group 3 than in groups 1 and 2 (p < 0.05) and higher body mass index in group 2. There were more patients receiving medications, including antiplatelet agents, P-blockers, and nitrates, in group 3 than in groups 1 and 2 (p < 0.05), as shown in Table 2.

Among the three groups, there was an inverse association between the extent of coronary artery calcification and endothelium-dependent FMD (6.9 ± 0.6% vs 5.3 ± 0.3% vs 3.7 ± 0.3%, respectively; p < 0.001), as shown in Table 3 and Figure 1, top, A. But no significant association existed between the CCS and endothelium-independent NMD (Fig 1, bottom, B). Both hsCRP and MCP-1 revealed no significant difference among the three groups (p = not significant), as shown in Table 3 and Figure 2. On the contrary, serum levels of hsCRP and MCP-1 were shown to be correlated significantly with endothelium-dependent FMD (r = — 0.211, p = 0.019; and r = — 0.188, p = 0.037, respectively) but not with endothelium-independent NMD (p = not significant), By multivariate analysis, enhanced coronary calcification was a strong independent predictor of endothelial dysfunction (p < 0.001).

Discussion

To our knowledge, this is the first study to demonstrate that coronary calcification determined by EBCT is strongly related to endothelial dysfunction assessed by peripheral brachial ultrasonography in patients with suspected CAD. In addition, serum levels of hsCRP and MCP-1, although not related to coronary calcification, were also found to be associated with endothelial function.

Peripheral brachial ultrasonographyAtherosclerotic calcification could begin as early as the second decade of life, just after fatty streak formation.- Calcium precipitates in diseased coronary arteries by a mechanism similar to that found in active bone formation and remodeling. Schmer-mund and colleagues showed that the vast majority of patients with acute coronary syndromes and documented CAD have identifiable coronary calcium detected by EBCT. Coronary artery calcium is intimately associated with coronary atherosclerotic plaque development, but the presence or absence of calcium does not allow for reliable distinction between unstable vs stable plaque. It can be speculated that coronary arterial calcification may represent an attempt to prevent acute coronary syndrome due to plaque rupture by strengthening weakened atherosclerotic plaque prone to rupture. The latest news from Canadian Neighbor Pharmacy is collected on its official website.

During the past 2 decades, it has become evident that the vascular endothelium is a highly active organ that plays a key role in the regulation of vascular tone and maintenance of vascular homeostasis. Endothelial dysfunction is characterized by a reduction of the bioavailability of vasodilators, particularly nitric oxide, and could predict further cardiovascular events. Impaired FMD in the brachial artery has been proved to be closely correlated with endothelial dysfunction in patients with CAD. In this study, enhanced coronary artery calcification were found to be significantly related to endothelial dysfunction in patients with suspected CAD, suggesting that the process of calcium precipitation in diseased coronary arteries is closely associated with endothelial dysfunction, an early sign of atherosclerosis. Further studies are needed to clarify the exact interaction between calcium deposition and shear stress-stimulated nitric oxide production by endothelial cells.

Increasing evidence suggests that atherosclerosis is an inflammatory disease. CRP, a serologic marker of inflammation, has been shown to be associated with the risk of future coronary events. However, studies of the relationship between CRP and coronary artery calcification in asymptomatic population did not reveal consistent results. The reasons for the lack of association between CRP and coronary artery calcification, in contrast to a more consistent association of CRP with clinical events, are not clear. Coronary arteries with higher calcium content may not necessarily exhibit more active inflammatory activity, as there may be several mechanisms responsible for the development of atherosclerosis. Park and coworkers found that CCSs and plasma CRP levels provided incremental information regarding the risk of clinical cardiovascular events in asymptomatic, nondiabetic subjects in the South Bay Heart Watch Study. Both CRP and coronary calcification may reflect different mechanisms that lead to clinical events and provide additional benefits for risk stratification of CAD. The MCP-1, which exhibits its most potent activity toward monocytes, rapidly causes rolling monocytes to adhere firmly onto endothelial cells and subsequent infiltration into the subendothelial space. In this study, MCP-1 was shown to be related to endothelial dysfunction. But lack of association between MCP-1 and coronary calcification again implies a different mechanism of involvement in atherosclerosis.

In conclusion, we demonstrated that enhanced coronary artery calcification is significantly related to endothelium dysfunction in patients with suspected CAD but not related to hsCRP or MCP-1. Endothelial dysfunction may play an important role in the process of coronary artery calcification.

Fig1

Figure 1. The percentage changes of endothelium-dependent FMD (top, A) and endothelium-independent NMD (bottom, B) in the three patient groups.

Fig2

Figure 2. The percentage changes of hsCRP (top, A) and MCP-1 (bottom, B) in the three patient groups.

Table 1

Characteristics Group 1 (CCS = 0) [n = 26] Group 2 (CCS = 1-199) [n = 50] Group 3 (CCS a 200) [n = 48] p Value
Age, yr 58 ± 3 66 ± 1 73 ± 1 < 0.05
Male gender 14 (54) 29 (58) 35 (73) 0.175
Body mass index 23.6 ± 0.4 26.0 ± 0.6 24.1 ± 0.5 < 0.05
Smoking status
Current smokers 6(23) 3(6) 7 (15) 0.058
Never-smokers 18 (69) 31 (62) 26 (54)
Former smokers 2(8) 16(16) 15 (31)
Exercise habits 4(15) 18 (36) 11 (23) 0.118
Family history of CAD 5(19) 10 (20) 8(17) 0.787
Systemic hypertension 7 (27) 26 (52) 31 (65) < 0.05
Diabetes mellitus 2 (8) 9(18) 15 (31) < 0.05
Hypercholesterolemia (total cholesterol 10 (39) 19 (38) 13 (27) 0.447
a 200 mg/dL)
Triglycerides, mg/dL 150 ± 17 142 ± 8 128 ± 13 0.448
High-density lipoproteins, mg/dL 52 ± 4 49 ± 3 45 ± 2 0.211
Fasting glucose, mg/dL 96 ± 5 104 ± 4 110 ± 4 0.081
Uric acid, mg/dL 6.6 ± 0.3 6.6 ± 0.2 6.6 ± 0.3 0.982
Creatinine, mg/dL 1.0 ± 0.1 1.0 ± 0.1 1.2 ± 0.1 0.145
Positive treadmill exercise test or 16 (62) 30 (60) 28 (58) 0.656
thallium scan results

Table 2—Medications of 124 Studied Patients in Three Groups

Variables Group 1 (CCS = 0) [n = 26] Group 2 (CCS = 1-199) [n = 50] Group 3 (CCS a 200) [n = 48] p Value
Antiplatelet agents 6(23) 30 (60) 38 (79) < 0.05
P-Blockers 7 (27) 20 (40) 27 (56) < 0.05
Calcium-channel blockers 8(31) 19 (38 26 (54) 0.103
Nitrates 6 (23) 14 (28) 23 (48) < 0.05
a-Blockers 1(4) 5 (10) 9 (19) 0.144
Diuretics 0 (0) 9 (18) 8(17) 0.072
Angiotensin-converting enzyme inhibitors 3 (12) 7 (14) 10 (21) 0.507
Angiotensin II receptor blockers 2 (8) 10 (20) 8(17) 0.381
Statins 8 (31) 13 (26) 14 (29) 0.893

Table 3—Comparison of Baseline Parameters

Variables Group 1 (CCS = 0) [n = 26] Group 2 (CCS = 1-199) [n = 50] Group 3 (CCS > 200) [n = 48] p Values
Baseline diameter, mm 3.4 ± 0.1 3.4 ± 0.1 3.6 ± 0.1 0.07
FMD, % 6.9 ± 0.6 5.3 ± 0.3 3.7 ± 0.3 < 0.001
NMD, % 16.7 ± 1.4 15.5 ± 0.8 13.0 ± 1.0 0.05
hsCRP, mg/dL 1.5 ± 0.4 2.2 ± 0.4 2.7 ± 0.4 0.219
MCP-1, pg/mL 206 ± 19 229 ± 13 216 ± 13 0.547