Research ArticleClinical Investigations

Determinants of Extraaortic Arterial 18F-FDG Accumulation in Asymptomatic Cohorts: Sex Differences in the Association with Cardiovascular Risk Factors and Coronary Artery Stenosis

Koichiro Kaneko, Tomohiro Kawasaki, Satoru Masunari, Tsuyoshi Yoshida and Junichi Omagari
Journal of Nuclear Medicine April 2013, 54 (4) 564-570; DOI: https://doi.org/10.2967/jnumed.112.111930

Abstract

The objective of this study was to evaluate extraaortic arterial 18F-FDG accumulation in asymptomatic cohorts by sex and to clarify the association between extraaortic arterial 18F-FDG accumulation and cardiovascular risk factors (CRFs) and coronary artery stenosis (CAS). Methods: Five hundred twenty-one asymptomatic individuals (351 men and 170 women) who underwent cancer and CAS screening were enrolled. We evaluated extraaortic arterial 18F-FDG accumulation in the carotid artery (CA) and iliofemoral artery (IFA) and classified the accumulation patterns into 3 types. Type 1 patients had no extraaortic arterial 18F-FDG accumulation, type 2 had accumulation in either the CA or the IFA, and type 3 had accumulation in both the CA and IFA. CRFs (age, low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, triglyceride concentration, visceral abdominal fat, hypertension, diabetes, and smoking) and significant CAS were examined in relation to each accumulation type. Results: The men showed more extensive extraaortic arterial 18F-FDG accumulation than the women. Type 3 accumulation (60.4% vs. 37.1%, P < 0.0001) was more frequently observed in men, whereas type 2 (34.2% vs. 44.7%, P = 0.02) and type 1 (5.4% vs. 18.2%, P < 0.0001) accumulation were more frequent in women. The CRFs other than smoking tended to be worse with extensive extraaortic arterial 18F-FDG accumulation. A multivariate logistic regression analysis showed that hypertension, age, LDL cholesterol, triglyceride, and visceral abdominal fat were significantly associated with type 3 accumulation in men, and LDL cholesterol and HDL cholesterol (inversely) were significantly associated with type 3 accumulation in women. CAS was found in 4.2% (9/212) of male patients and in 1.6% (1/63) of female patients with type 3 accumulation, whereas no CAS was found in the other 2 types. Conclusion: The men showed more extensive extraaortic arterial 18F-FDG accumulation than the women. LDL cholesterol was associated with extensive extraaortic arterial 18F-FDG accumulation in both sexes, but the other CRFs associated with extensive extraaortic 18F-FDG arterial accumulation differed between the sexes. The type 3 accumulation was considered to pose a risk of CAS, especially in male patients, whereas non–type 3 accumulation presented little risk.

Atherosclerosis is recognized as an inflammatory disorder, and previous studies showed that inflammation of atherosclerotic plaques could be evaluated by 18F-FDG PET imaging, especially in macrophage-related vascular inflammation (1–3). The prevalence and intensity of 18F-FDG accumulation in large arteries generally increase with aging (4,5). 18F-FDG accumulation in the abdominal aorta and iliofemoral artery (IFA) correlates with age and hypercholesterolemia (6). In addition, metabolic syndrome is also associated with carotid plaque 18F-FDG accumulation (7,8). A high prevalence of 18F-FDG accumulation in the femoral artery or carotid artery (CA) was also detected in patients with coronary artery disease (CAD) (6–8).

A histologic analysis of CA plaque revealed that men had more unstable CA plaque, including more features of inflammation, than did women (9). An in vivo carotid MR imaging–based study revealed that the presence of atherosclerotic components such as a thin or ruptured fibrous cap and lipid-rich necrotic core in CA was more common in men (10). Moreover, in CAD, sex differences in plaque morphology have been described that point to a higher prevalence of fresh thrombus and plaque rupture in men (11,12).

We hypothesized that extensive extraaortic arterial 18F-FDG accumulation such as that in CA and IFA may be associated with cardiovascular risk factors (CRFs) and coronary artery stenosis (CAS) and that male and female patients may show different extraaortic arterial 18F-FDG distribution. In addition different associations may also exist in extraaortic arterial 18F-FDG accumulation, CRFs, and CAS according to sex differences.

The aims of this study were thus to explore sex differences in extraaortic arterial 18F-FDG distribution and to clarify such differences in the associations among extraaortic arterial 18F-FDG accumulation, CRFs, and CAS.

MATERIALS AND METHODS

Patients

This retrospective study was approved by the institutional review board of Koga Hospital 21, and direct informed consent was waived. This retrospective study included 521 asymptomatic consecutive patients (351 men and 170 women; age range, 28–84 y; mean age, 57.3 and 59.7 y, respectively) who were involved in a screening program using 18F-FDG PET/CT and coronary MR angiogram (MRA) run by our institution from November 2007 to May 2010. They underwent 18F-FDG PET/CT and coronary MRA to detect cancer and CAS, and these imaging modalities showed that none of the patients had a major disease. Thirteen patients had a history of curative operation for malignancy, and 2 patients had gastric and bladder cancer, which was found by the 18F-FDG PET/CT examination. No patients received oncologic treatment at the time of examination.

This study excluded the patients with a history of CAD or coronary revascularization, those who had received statin therapy for dyslipidemia, those who had uncontrolled diabetes (hemoglobin A1c > 9.0%) or had received insulin therapy for diabetes, and those who had had 18F-FDG accumulation in the cervical portion, which interfered with the evaluation of CA accumulation such as diffuse thyroidal accumulation or high sternomastoid muscle accumulation.

18F-FDG PET/CT Protocol

The patients fasted for at least 6 h before 18F-FDG administration. All patients received an intravenous injection of 18F-FDG (3.7 MBq/kg) and then rested for 1 h before the scan started. Images were acquired using a True Point Biograph 40 PET/CT scanner (Siemens), which integrates 40-slice multidetector CT. Low-dose non–contrast-enhanced CT (tube voltage, 120 kV; effective tube current, 80 mA) that covered from the top of the skull to the proximal thigh was performed for attenuation correction and precise anatomic location, and then emission images for 2 min per position were obtained in 3-dimensional mode. The PET set was reconstructed using the Fourier rebinning ordered-subset expectation maximization 2-dimensional method, with 2 full iterations of 8 subsets, and the full width at half maximum was 4.2 mm.

Coronary MRA and CT Angiography (CTA) Protocol

All patients (n = 521) underwent cardiac MR imaging, performed with a 1.5-T scanner (Achieva; Philips) equipped with a 5-channel cardiac coil. Isosorbide dinitrate (5 mg) was administered sublingually to the patient before he or she underwent MR imaging. The whole-heart coronary MRAs were obtained using a free-breathing 3-dimensional segmented steady-state free precision sequence with electrocardiogram triggering. To compensate for the respiratory motion, prospective diaphragmatic navigator gating was used with no drift correction and the 5-mm gating window. The imaging parameters for the 3-dimensional segmented steady-state free precession sequence were as follows: repetition time/echo time, 4.0/2.0; flip angle, 85°; field of view, 300 × 270 mm; matrix, 224 × 220; and slice thickness/reconstruction, 1.6/0.8 mm. Spectral presaturation with inversion recovery was applied to suppress epicardial fat signals. If available, a coronary CT angiography (CTA) examination was performed in the patients who showed significant CAS on their MRA (n = 5). Coronary CTA was performed using a LightSpeed VCT (GE Healthcare), which integrates a 64-slice multidetector CT scanner. The CTA protocol was the same as that used in our previous study (13). All patients underwent 18F-FDG PET/CT and coronary MRA within a 2-d period.

18F-FDG PET/CT Findings

An experienced nuclear medicine physician, masked to the clinical characteristics of the patients, visually evaluated extraaortic arterial 18F-FDG accumulation in the CA and IFA. The scan was interpreted as positive if each artery showed linear activity of 18F-FDG accumulation higher than the background level. The accumulation pattern was classified into 3 types. Type 1 patients had no extraaortic accumulation, type 2 had accumulation in either the CA or the IFA, and type 3 had accumulation in both the CA and the IFA (Fig. 1).

FIGURE 1.
FIGURE 1.

Maximum-intensity-projection images of PET/CT are shown. Extraaortic arterial 18F-FDG accumulation was classified into 3 types. (A) Type 1 is no extraaortic arterial 18F-FDG accumulation. (B and C) Type 2 is arterial 18F-FDG accumulation in either CA or IFA. (D) Type 3 is arterial 18F-FDG accumulation in both CA and IFA. In B–D, dotted arrows point to CA accumulation, and solid arrows point to IFA accumulation.

Coronary MRA and CTA Findings

The following 9 segments of the coronary artery as defined in the guidelines of the American Heart Association were evaluated for stenosis (14): the proximal, middle, and distal segments of the right coronary artery (nos. 1–3); the left main coronary artery (no. 5); the proximal, middle, and distal segments of the left anterior descending artery (nos. 6–8); and the proximal and distal segments of the left circumflex artery (nos. 11 and 13). The segments were classified as having significant stenosis (≥75%) or no significant stenosis at visual assessment. The appearance of a reduction in segmental diameter or a loss of signal intensity on MR images was considered to be indicative of a significant CAS.

The subsequent CTA images were also assessed to compare them with the MRA findings, and any narrowing of the normal contrast-enhanced lumen to <50% that could be identified by multiplanar reconstructions or cross-sectional images was defined as significant CAS. Two observers independently evaluated the coronary MRA and CTA images. The observers were masked to the clinical character and 18F-FDG PET/CT findings of the patients. Disagreement between the 2 observers was settled by a consensus reading. The incidences of significant CAS were assessed and compared between the type 3 accumulation and the 2 other types in both sexes.

CRFs

Eight CRFs (age, LDL cholesterol, HDL cholesterol, triglyceride concentration, visceral abdominal fat [VAT], hypertension, diabetes, and current smoking) were examined in relation to each accumulation type. Patients were classified as having hypertension if they had a systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg (15) or were taking antihypertensive medications. Patients were classified as having diabetes if they had a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5% (16) or were taking oral antidiabetic medication. Hemoglobin A1c values were converted from Japan Diabetes Society values to National Glycohemoglobin Standardization Program values (17). VAT volumes were measured on the CT images obtained by the same PET/CT scanner. A cross-sectional 5-mm slice at the umbilical level was obtained, and the attenuation range of −60 to −160 Hounsfield units was used to identify adipose tissue. A computation of the surface area from the CT scans was conducted with volume analysis software (Fat Checker; J-MAC System). The total abdominal fat area was calculated using all pixels within the attenuation range, and VAT was defined as the area of adipose tissue within the edge of the abdominal wall. The incidences or values of the 8 CRFs were compared among the 3 types of 18F-FDG accumulation, and the CRFs that were significantly associated with type 3 accumulation were assessed in both sexes.

Statistical Analysis

Incidences were compared using a χ2 test, and if necessary, a Bonferroni adjustment was added. Values were compared using the nonparametric Mann–Whitney U test or the Kruskal–Wallis test. A multiple logistic regression analysis examining the associations between CRFs and the type 3 accumulation pattern was performed. Probability values of less than 0.05 were considered significant.

RESULTS

The clinical features of the patients are summarized in Table 1. The men showed more extensive extraaortic arterial 18F-FDG accumulation than the women. Type 3 accumulation was more frequently observed in men than women (60.4% vs. 37.1%, P < 0.0001), whereas type 2 (34.2% vs. 44.7%, P = 0.02) and type 1 (5.4% vs. 18.2%, P < 0.0001) accumulation were more frequent in women (Table 2).

View this table:
TABLE 1

Clinical Features of Patients

View this table:
TABLE 2

Sex Differences in Incidence of Each Accumulation Pattern

The incidences of the CRFs other than smoking tended to be higher with extensive extraaortic arterial 18F-FDG accumulation, and the incidence of hypertension was significantly higher in male patients with type 3 accumulation than in the other 2 types (38.2% vs. 10.5% and 19.2%, P = 0.02 and 0.0003, respectively; Table 3). In male patients with type 3 accumulation, the age, VAT, and triglyceride values were significantly higher than in male patients with the other 2 accumulation types, and the LDL cholesterol values of the men with type 3 accumulation were also significantly higher than those of the type 1 men (P = 0.03, Table 3). No significant difference was found in HDL cholesterol values (Table 3).

View this table:
TABLE 3

Comparisons of CRFs Between Type 3 and Other Types of Patients

In the women, VAT and HDL cholesterol values were significantly higher and lower, respectively, in the type 3 patients than in patients with the other 2 types of accumulation, and the LDL cholesterol and triglyceride values were also significantly higher than those of the type 1 patients (P = 0.03 to <0.0001, Table 3). The ages of the type 3 patients were significantly higher than those of the type 1 patients (P < 0.0001, Table 3), but no significant difference was found between the type 2 and type 3 patients.

The multivariate logistic regression analysis showed that hypertension, age, LDL cholesterol, triglyceride, and VAT were significantly associated with type 3 accumulation in men (P = 0.045 to <0.0001, Table 4), and LDL cholesterol and HDL cholesterol (inversely) were significantly associated with type 3 accumulation in women (P = 0.047 to 0.02, Table 4).

View this table:
TABLE 4

Odds Ratio and 95% Confidence Intervals for Type 3 Accumulation

Significant CAS was found in 4.2% (9/212) of the male type 3 patients and 1.6% (1/63) of the female type 3 patients, but no CAS was found in the patients with the other 2 accumulation types. A case of a male type 3 patient with significant CAS is shown in Figure 2. The incidence of CAS was significantly higher in type 3 than in non–type 3 patients (P = 0.01) in the men but not in the women. We performed a subsequent coronary CTA in 5 patients, and we confirmed severe CAS in all 5. The details of the patients with significant CAS are given in Table 5.

FIGURE 2.
FIGURE 2.

A 56-y-old man with significant CAS. (A) Maximum-intensity-projection image of PET/CT showed arterial 18F-FDG accumulation in both CA and IFA, defined as type 3 accumulation (arrows). (B) Curved planar reconstruction of coronary MRA image showed significant stenosis in middle segment of left anterior descending artery (arrow). (C) Curved planar reconstruction of patient’s coronary CTA images also showed significant stenosis in same artery (arrow).

View this table:
TABLE 5

Details of Patients with CAS

DISCUSSION

Arterial wall 18F-FDG accumulation in the vessel wall is related to macrophage infiltration, and it indicates vessel wall inflammation (3). In addition, arterial 18F-FDG accumulation is higher in plaque with a lipid-rich necrotic core than in plaques with collagen and calcification (18).

It has long been recognized that the incidence of CAD is significantly lower in women than in men, particularly women in the premenopausal stage. In premenopausal women, compared with age-matched men, the lower prevalence of CAD has been explained by differences in body fat distribution, plasma lipoprotein levels, and indices of glucose-insulin homeostasis. Endogenous female sex hormones, especially estrogens, are thought to be cardioprotective via multiple mechanisms: increased HDL cholesterol, decreased LDL cholesterol, and release of vasodilators such as nitric oxide and prostacyclin from vessel walls (19). Additionally, estrogen seems to contribute to glucose homeostasis via increased glucose transport into the cell (19).

Hellings et al. revealed that CA plaques obtained from women contain less fat and macrophages and more smooth muscle than those from men (9). Another study showed that men are more likely to have CA plaque characterized by the presence of lipid-rich necrotic core, a thin or ruptured fibrous cap, and intraplaque hemorrhage than women (10). Our present findings show that the men had more extensive extraaortic arterial 18F-FDG accumulation than the women, and our findings are in agreement with previous results.

Several studies showed that 18F-FDG accumulation in the aorta and IFA correlated with age and hypercholesterolemia but not smoking, diabetes, hypertension, or obesity (6,20). On the other hand, Bucerius et al. reported that carotid 18F-FDG accumulation was highly prevalent in the CAD population and was associated with obesity, age, smoking, hypertension, and male sex (8). In the present study, all of the CRFs examined except smoking tended to be worse with extensive extraaortic arterial 18F-FDG accumulation, and significant differences were found in most of the CRFs between the type 3 and non–type 3 patients. Our results indicate that extraaortic arterial 18F-FDG accumulation in the CA and IFA is related to many CRFs, and they also indicate that type 3 accumulation represents a state of more advanced atherosclerosis.

Our multivariate logistic regression analysis showed a male preponderance in several CRFs, which were significantly associated with extensive extraaortic arterial 18F-FDG accumulation. A previous study showed that male sex is associated with carotid 18F-FDG accumulation and other CRFs, such as obesity (8). Other research demonstrated sex differences in plaque morphology or the degree of arterial 18F-FDG accumulation (9–12,21). We also speculated that male sex itself is an important CRF, and our present findings suggest that many other CRFs enhance extraaortic arterial 18F-FDG accumulation in concert with male sex.

High serum levels of LDL cholesterol and low serum levels of HDL cholesterol are the major predictors of atherosclerotic CAD (22,23). Our present findings suggest that LDL cholesterol is the only common CRF that is significantly associated with extensive extraaortic arterial 18F-FDG accumulation in both sexes. In our results, age and VAT were thought to have strong associations with extensive extraaortic arterial 18F-FDG accumulation in men. Age was found to be the most significant and consistent factor correlated with arterial 18F-FDG accumulation (6). Here we made comparisons by sex and found that age did not have a significant association with extraaortic arterial 18F-FDG accumulation in women. We suspect that estrogen exposure earlier in life could be a cause of this result.

VAT is a key player in the development of metabolic syndrome (24). Lemieux et al. investigated sex differences of body fat distribution and reported that men had higher VAT volume whereas women had higher subcutaneous fat tissue (25). Lear et al. claimed that VAT is the primary adiposity associated with atherosclerosis and likely represents an additional risk factor for carotid atherosclerosis in men (26). Shimizu et al. contended that VAT accumulation acts in concert with CRF accumulation to increase the risk for CAD (27). Our results showed that men had a higher VAT volume and a significant association with extensive extraaortic arterial 18F-FDG accumulation and suggest that VAT both played a key role in the extensive extraaortic arterial 18F-FDG accumulation in the men examined and was related to the development of CAD.

We found that diabetes was not significantly associated with extensive extraaortic arterial 18F-FDG accumulation in either sex. Kim et al. reported that impaired glucose tolerance and type 2 diabetes were associated with vascular inflammation in carotid atherosclerosis detected by 18F-FDG PET (28), a finding that differs from our results. However, they investigated the degree of 18F-FDG accumulation using the target-to-background ratio in patients with different glucose tolerance levels (28) rather than arterial 18F-FDG distribution. Our results suggest that diabetes may be associated with the degree of arterial 18F-FDG accumulation rather than distribution.

In our study, significant CAS was found only in the type 3 patients (4.2% of the men and 1.6% of the women), and no CAS was found in the non–type 3 patients. Several studies have shown an association between CAD and CA inflammation (8,21). Carotid plaque morphology as assessed by either ultrasound or angiography has been related to coronary plaque morphology and coronary morbidity (29,30). Our present findings indicate that asymptomatic type 3 patients, especially male patients, had a risk of significant CAS. Conversely, non–type 3 patients were considered to have little risk of significant CAS.

Our study has some limitations. First, a major limitation of the present study is that it was retrospective, and further prospective studies would be beneficial. Second, we first evaluated CAS using coronary MRA. Although coronary MRA is considered a useful modality that can noninvasively detect significant CAD with high sensitivity and moderate specificity, it also has a high negative predictive value (31). Third, we evaluated arterial 18F-FDG distribution but not the degree of arterial 18F-FDG accumulation (i.e., standardized uptake value or target to background) because we used 60-min 18F-FDG as the optimal circulation time point, as is commonly used in oncology PET studies. Previous studies recommended longer optimal circulation times, preferably at least 90 min (32), but an optimal circulation time point has not yet been standardized (32,33).

CONCLUSION

Men showed more extensive extraaortic arterial 18F-FDG accumulation than women. LDL cholesterol was associated with extensive extraaortic arterial inflammation in both sexes, and the other CRFs associated with extensive extraaortic arterial inflammation differed between the sexes. The most extensive type 3 accumulation was considered to pose a risk of significant CAS, especially in male patients, whereas non–type 3 accumulation presented little risk.

DISCLOSURE

The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734. No potential conflict of interest relevant to this article was reported.

Footnotes

  • Published online Mar. 7, 2013.

REFERENCES

  1. 1.↵
    1. Rudd JH,
    2. Warburton EA,
    3. Fryer TD,
    4. et al
    . Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation. 2002;105:2708–2711.
    OpenUrlAbstract/FREE Full Text
  2. 2.
    1. Davies JR,
    2. Rudd JH,
    3. Fryer TD,
    4. et al
    . Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke. 2005;36:2642–2647.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Tawakol A,
    2. Migrino RQ,
    3. Bashian GG,
    4. et al
    . In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–1824.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Bural GG,
    2. Torigian DA,
    3. Chamroonrat W,
    4. et al
    . FDG-PET is an effective imaging modality to detect and quantify age-related atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging. 2008;35:562–569.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Yun M,
    2. Yeh D,
    3. Araujo LI,
    4. et al
    . F-18 FDG uptake in the large arteries: a new observation. Clin Nucl Med. 2001;26:314–319.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Yun M,
    2. Jang S,
    3. Cucchiara A,
    4. et al
    . 18F FDG uptake in the large arteries: a correlation study with the atherogenic risk factors. Semin Nucl Med. 2002;32:70–76.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Tahara N,
    2. Kai H,
    3. Yamagishi S,
    4. et al
    . Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. J Am Coll Cardiol. 2007;49:1533–1539.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Bucerius J,
    2. Duivenvoorden R,
    3. Mani V,
    4. et al
    . Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients: FDG-PET and CT imaging study. JACC Cardiovasc Imaging. 2011;4:1195–1205.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Hellings WE,
    2. Pasterkamp G,
    3. Verhoeven BA,
    4. et al
    . Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomy. J Vasc Surg. 2007;45:289–296.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Ota H,
    2. Reeves MJ,
    3. Zhu DC,
    4. et al
    . Sex differences in patients with asymptomatic carotid atherosclerotic plaque: in vivo 3.0-T magnetic resonance study. Stroke. 2010;41:1630–1635.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Rittersma SZ,
    2. van der Wal AC,
    3. Koch KT,
    4. et al
    . Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: a pathological thrombectomy study in primary percutaneous coronary intervention. Circulation. 2005;111:1160–1165.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Virmani R,
    2. Kolodgie FD,
    3. Burke AP,
    4. et al
    . Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262–1275.
    OpenUrlFREE Full Text
  13. 13.↵
    1. Kawasaki T,
    2. Koga S,
    3. Koga N,
    4. et al
    . Characterization of hyperintense plaque with noncontrast T(1)-weighted cardiac magnetic resonance coronary plaque imaging: comparison with multislice computed tomography and intravascular ultrasound. JACC Cardiovasc Imaging. 2009;2:720–728.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Scanlon PJ,
    2. Faxon DP,
    3. Audet AM,
    4. et al
    . ACC/AHA guidelines for coronary angiography: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography)—developed in collaboration with the Society for Cardiac Angiography and Interventions. J Am Coll Cardiol. 1999;33:1756–1824.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Ogihara T,
    2. Kikuchi K,
    3. Matsuoka H,
    4. et al.
    Japanese Society of Hypertension Committee: the Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2009). Hypertens Res. 2009;32:3–107.
    OpenUrlPubMed
  16. 16.↵
    1. Kuzuya T,
    2. Nakagawa S,
    3. Satoh J,
    4. et al
    . Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus: report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus. Diabetes Res Clin Pract. 2002;55:65–85.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Kashiwagi A,
    2. Kasuga M,
    3. Araki E,
    4. et al
    . International clinical harmonization of glycated hemoglobin in Japan: from Japan Diabetes Society to National Glycohemoglobin Standardization Program values. Diabetol Int. 2012;3:8–10.
    OpenUrlCrossRef
  18. 18.↵
    1. Silvera SS,
    2. Aidi HE,
    3. Rudd JH,
    4. et al
    . Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries. Atherosclerosis. 2009;207:139–143.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Pérez-López FR,
    2. Larrad-Mur L,
    3. Kallen A,
    4. Chedraui P,
    5. Taylor HS
    . Gender differences in cardiovascular disease: hormonal and biochemical influences. Reprod Sci. 2010;17:511–531.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Tatsumi M
    . Cohade C, Nakamoto Y, Wahl RL. Fluorodeoxyglucose uptake in the aortic wall at PET/CT: possible finding for active atherosclerosis. Radiology. 2003;229:831–837.
    OpenUrlPubMed
  21. 21.↵
    1. Rudd JH,
    2. Myers KS,
    3. Bansilal S,
    4. et al
    . Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: a prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study. Circ Cardiovasc Imaging. 2009;2:107–115.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Gordon T,
    2. Castelli WP,
    3. Hjortland MC,
    4. Kannel WB,
    5. Dawber TR
    . High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62:707–714.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Assmann G,
    2. Cullen P,
    3. Kannenberg F,
    4. Schulte H
    . Relationship between phytosterol levels and components of the metabolic syndrome in the PROCAM study. Eur J Cardiovasc Prev Rehabil. 2007;14:208–214.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Matsuzawa Y,
    2. Funahashi T,
    3. Nakamura T
    . The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism. J Atheroscler Thromb. 2011;18:629–639.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Lemieux S,
    2. Prud'homme D,
    3. Bouchard C,
    4. Tremblay A,
    5. Després JP
    . Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am J Clin Nutr. 1993;58:463–467.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Lear SA,
    2. Humphries KH,
    3. Kohli S,
    4. Chockalingam A,
    5. Frohlich JJ,
    6. Birmingham CL
    . Visceral adipose tissue accumulation differs according to ethnic background: results of the Multicultural Community Health Assessment Trial (M-CHAT). Am J Clin Nutr. 2007;86:353–359.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Hiuge-Shimizu A,
    2. Kishida K,
    3. Funahashi T,
    4. et al
    . Coexistence of visceral fat and multiple risk factor accumulations is strongly associated with coronary artery disease in Japanese (The VACATION-J Study). J Atheroscler Thromb. 2012;19:657–663.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Kim TN,
    2. Kim S,
    3. Yang SJ,
    4. et al
    . Vascular inflammation in patients with impaired glucose tolerance and type 2 diabetes: analysis with 18F-fluorodeoxyglucose positron emission tomography. Circ Cardiovasc Imaging. 2010;3:142–148.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Rothwell PM,
    2. Villagra R,
    3. Gibson R,
    4. Donders RC,
    5. Warlow CP
    . Evidence of a chronic systemic cause of instability of atherosclerotic plaques. Lancet. 2000;355:19–24.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Honda O,
    2. Sugiyama S,
    3. Kugiyama K,
    4. et al
    . Echolucent carotid plaques predict future coronary events in patients with coronary artery disease. J Am Coll Cardiol. 2004;43:1177–1184.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Kato S,
    2. Kitagawa K,
    3. Ishida N,
    4. et al
    . Assessment of coronary artery disease using magnetic resonance coronary angiography: a national multicenter trial. J Am Coll Cardiol. 2010;56:983–991.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Rudd JH,
    2. Myers KS,
    3. Bansilal S,
    4. et al
    . Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med. 2008;49:871–878.
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    1. Menezes LJ,
    2. Kotze CW,
    3. Hutton BF,
    4. et al
    . Vascular inflammation imaging with 18F-FDG PET/CT: when to image? J Nucl Med. 2009;50:854–857.
    OpenUrlAbstract/FREE Full Text
  • Received for publication July 30, 2012.
  • Accepted for publication November 5, 2012.
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Bookmark this article

Jump to section

Keywords