Association between lower extremity arterial calcification and coronary arterial calcification in a population at increased risk of cardiovascular disease.

INTRODUCTION: There is conflicting evidence whether lower extremity arterial calcification coincides with coronary arterial calcification (CAC). The aims of this study were to investigate the associations between (1) femoral and crural calcification with CAC, and (2) femoral and crural calcification pattern with CAC. RESEARCH DESIGN AND METHODS: This cross-sectional study included 405 individuals (74% men, 62.6±10.9 years) from the ARTEMIS cohort study at high risk of cardiovascular disease (CVD) who underwent a CT scan of the femoral, crural and coronary arteries. High CVD risk was defined as history/presence of cerebrovascular disease, coronary artery disease, abdominal aortic aneurysm, renal artery stenosis, peripheral artery disease or CVD risk factors: diabetes mellitus type 2, hypertension, hyperlipidemia. Calcification score within each arterial bed was expressed in Agatston units. Dominant calcification patterns (intimal, medial, absent/indistinguishable) were determined via a CT-guided histologically validated scoring algorithm. Multivariable-adjusted multinomial logistic regression analyses were used. Replication was performed in an independent population of individuals with diabetes mellitus type 2 (Early-HFpEF cohort study). RESULTS: Every 100-point increase in femoral and crural calcification score was associated with 1.23 (95% CI=1.09 to 1.37, p<0.001) and 1.28 (95% CI=1.11 to 1.47, p=0.001) times higher odds of having CAC within tertile 3 (high) versus tertile 1 (low), respectively. The association appeared stronger for crural versus femoral arteries. Moreover, the presence of femoral intimal (OR=10.81, 95% CI=4.23 to 27.62, p<0.001), femoral medial (OR=10.37, 95% CI=3.92 to 27.38, p<0.001) and crural intimal (OR=6.70, 95% CI=2.73 to 16.43, p<0.001) calcification patterns were associated with higher odds of having CAC within tertile 3 versus tertile 1, independently from concomitant calcification score. This association appeared stronger for intimal versus medial calcification patterns. The replication analysis yielded similar results. CONCLUSIONS: Higher femoral and crural calcification scores were associated with higher CAC. Moreover, the presence of femoral intimal, femoral medial and crural intimal calcification patterns was associated with increased CAC. It appears that arterial calcification is a systemic process which occurs simultaneously in various arterial beds.

An elevated ankle-brachial index is not a valid proxy for peripheral medial arterial calcification.

BACKGROUND AND AIMS: The ankle brachial index (ABI) is often used as a proxy for medial arterial calcification (MAC) in studies investigating MAC as a cardiovascular risk factor, but evidence supporting this hypothesis is sparse. This study aims to investigate the use of an elevated ABI as proxy for MAC, as visualized with computed tomography (CT). METHODS: Cross-sectional data of 718 participants with, or at risk of cardiovascular disease was used. The ABI was calculated using cutoffs >1.4 and > 1.3. The presence of MAC was assessed in the crural and femoral arteries by CT imaging. Modified Poisson regression was used to assess the association between an elevated ABI and the presence of MAC, and test characteristics were calculated. RESULTS: MAC was found in 25.0% of participants. An ABI >1.4 was found in 8.7% of participants, of whom 45.2% had MAC. An elevated ABI was significantly associated with the presence of MAC (RR 1.74, CI: 1.26-2.40). However, poor positive specific agreement (23.3%, CI: 13.9-34.3), sensitivity (15.7%, CI: 10.4-21.1) and positive predictive value (45.2%, CI: 32.8-57.5) were found. Despite good specificity (93.6%, CI: 91.6-95.7) the area under the receiving operator curve remained poor (54.7%, CI: 51.8-57.6). Negative specific agreement (84.5%, CI: 81.4-87.0) and negative predictive value (77.0%, CI: 73.7-80.2) were acceptable. CONCLUSIONS: An elevated ABI is insufficient to serve as a true diagnostic proxy for MAC. Studies that have drawn conclusions on the association between MAC and cardiovascular disease, solely based on the ABI, are likely to underestimate the found effects.

Intimal and medial calcification in relation to cardiovascular risk factors.

PURPOSE: To assess specific risk factors and biomarkers associated with intimal arterial calcification (IAC) and medial arterial calcification (MAC). METHODS: We conducted a cross-sectional study in patients with or at risk of vascular disease from the SMART study(n = 520) and the DCS cohort(n = 198). Non-contrast computed tomography scanning of the lower extremities was performed and calcification in the femoral and crural arteries was scored as absent, predominant IAC, predominant MAC or indistinguishable. Multinomial regression models were used to assess the associations between cardiovascular risk factors and calcification patterns. Biomarkers for inflammation, calcification and vitamin K status were measured in a subset of patients with IAC(n = 151) and MAC(n = 151). RESULTS: Femoral calcification was found in 77% of the participants, of whom 38% had IAC, 28% had MAC and 11% were scored as indistinguishable. The absolute agreement between the femoral and crural arteries was high(69%). Higher age, male sex, statin use and history of coronary artery disease were associated with higher prevalences of femoral IAC and MAC compared to absence of calcification. Smoking and low ankle-brachial-index (ABI) were associated with higher prevalence of IAC and high ABI was associated with less IAC. Compared to patients with IAC, patients with MAC more often had diabetes, have a high ABI and were less often smokers. Inactive Matrix-Gla Protein was associated with increased MAC prevalence, while osteonectin was associated with decreased risk of MAC, compared to IAC. CONCLUSIONS: When femoral calcification is present, the majority of the patients have IAC or MAC throughout the lower extremity, which have different associated risk factor profiles.

Hepatic fat is not associated with beta-cell function or postprandial free fatty acid response.

We evaluated the association of hepatic fat with beta-cell function estimated from the oral glucose tolerance test. In addition, we tested the hypothesis that postprandial free fatty acid (FFA) suppression after a meal tolerance test (MTT) is linked to hepatic fat. Individuals with normal glucose metabolism (NGM; n = 10 with low and n = 10 with high insulin secretion, matched for insulin sensitivity and sex), impaired glucose metabolism (IGM; n = 14), and type 2 diabetes mellitus (DM; n = 14) underwent a 75-g oral glucose tolerance test and MTT. beta-Cell function estimates were calculated from C-peptide using a mathematical model. Liver fat was quantified by proton magnetic resonance ((1)H-MR) spectroscopy. Area under the curve (AUC) of triglycerides (TG) and FFA responses during MTT represented postprandial lipid responses. Linear regression models were adjusted for age, sex, and additionally for insulin sensitivity for IGM/DM subjects. Liver fat content was equal for the NGM groups with low and high insulin secretion: 4.5% (2.6-6.0) (median, interquartile range) and 4.9% (2.3-7.8), respectively; liver fat percentages of IGM and diabetic subjects were significantly higher: 11.2 (6.7-21.1) and 10.0 (7.8-24.5). Liver fat showed a fairly strong, significant negative association with insulin sensitivity, but was not associated with beta-cell function. Significant associations of liver fat with fasting TG and AUC(TG) were shown in the total study population and in IGM/DM subjects separately. No relationship existed between fasting FFA or AUC(FFA) and liver fat. We conclude that fat accumulation in the liver is tightly linked to insulin sensitivity but not to beta-cell function. Furthermore, liver fat is associated with circulating TG levels, but not with FFA concentrations.