Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac MR (CMR) and to assess variation with image acquisition plane, demographics and LV function.
Methods and Results
End-diastolic LVMT was measured on CMR steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9mm and 6.3±1.1mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men were 7mm/9mm (long axis) and 7mm/8mm (short axis). Mean LVMT was positively associated with weight (0.02mm/kg, p=0.01) and body-surface-area (1.1mm/m2, p<0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower LV end-diastolic volume (0.01mm/ml, p<0.01), a lower LV end-systolic volume (−0.01mm/ml, p=0.01) and lower LV stroke volume (−0.01mm/ml, p<0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images.
Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.
magnetic resonance imaging; myocardial thickness; normal values
To identify treatable risk factors for aspiration in older adults—particularly those associated with sarcopenia – we examined tongue composition. We hypothesized that 1) isometric and swallowing posterior tongue strength would positively correlate with posterior tongue adiposity, and 2) healthy older adults who aspirate would have greater tongue adiposity than healthy older adults who did not aspirate.
Participants were 40 healthy adults, comprised of 20 aspirators (Mean age = 78 years) and 20 non-aspirators (Mean age = 81 years), as identified via flexible endoscopic evaluation of swallowing. Measures of maximal isometric posterior tongue strength and posterior swallowing tongue strength were acquired via tongue manometry. An index of posterior tongue adiposity was acquired via computed tomography for a 1 cm region of interest.
Posterior tongue adiposity was correlated with posterior tongue isometric (r = .32, p = 0.05) but not swallowing pressures (p > 0.05) as examined with separate partial correlation analyses. Tongue adiposity did not significantly differ as a function of age, gender, or aspiration status (p > 0.05).
Lower posterior isometric tongue strength was associated with greater posterior tongue adiposity. However, aspiration in healthy older adults was not affected by posterior tongue adiposity. This finding offers insight into the roles of tongue composition and strength in healthy older adults.
Tongue; Adiposity; Fat; Swallowing; Older Adults; Computed Tomography
Patients with type 2 diabetes (T2D) are at elevated risk for cardiovascular disease (CVD) events and mortality. Recent studies have assessed the impact of genetic variants affecting high-density lipoprotein cholesterol (HDL) concentrations on CVD risk in the general population. This study examined the utility of HDL-associated single nucleotide polymorphisms (SNPs) for CVD risk prediction in European Americans with T2D enrolled in the Diabetes Heart Study (DHS).
Genetic risk scores (GRS) of HDL-associated SNPs were constructed and evaluated for potential associations with mortality and with coronary artery calcified atherosclerotic plaque (CAC), a measure of subclinical CVD strongly associated with CVD events and mortality. Two sets of SNPs were used to construct GRS; while all SNPs were selected primarily for their impacts on HDL, one set of SNPs had pleiotropic effects on other lipid parameters, while the other set lacked effects on low-density lipoprotein cholesterol (LDL) or triglyceride concentrations.
The GRS were specifically associated with HDL concentrations (4.90 × 10-7 < p < 0.02) in models adjusted for age, sex, and body mass index (BMI), but were not associated with LDL or triglycerides. Cox proportional hazards regression analysis suggested the HDL-associated GRS had no impact on risk of CVD-mortality (0.48 < p < 0.99) in models adjusted for other known CVD risk factors. However, associations between several of the GRS and CAC were observed (3.85 × 10-4 < p < 0.03) in models adjusted for other known CVD risk factors.
The GRS analyzed in this study provide a tool for assessment of HDL-associated SNPs and their impact on CVD risk in T2D. The observed associations between several of the GRS and CAC suggest a potential role for HDL-associated SNPs on subclinical CVD risk in patients with T2D.
High-density lipoprotein cholesterol; Type 2 diabetes; Coronary artery calcified plaque; Mortality; Genetic risk score
This study aimed to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population.
Aortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial and it is unknown if this association extends to younger individuals.
We performed a prospective analysis of 6,685 participants in the Multi-Ethnic Study of Atherosclerosis. All subjects, aged 45-84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium (CAC) scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and non-fatal strokes, resuscitated cardiac arrest and cardiovascular death, while a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers and subclinical coronary atherosclerosis.
Over a median follow up of 5.8 [IQR 5.6, 5.9] years, adjusting for demographics and cardiovascular risk factors, subjects with AVC (n=894, 13.4%) had higher risks of cardiovascular (HR, 1.50; 95% CI, 1.10-2.03) and coronary (HR, 1.72; 95% CI, 1.19-2.49) events compared to those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for CAC substantially attenuated both cardiovascular (HR, 1.32; 95% CI: 0.98-1.78) and coronary (HR, 1.41; 95% CI, 0.98-2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR, 2.51; 95% CI, 1.22-5.21).
In this multiethnic MESA cohort, free of clinical cardiovascular disease, AVC predicts cardiovascular and coronary event risk independent of traditional risk factors and inflammatory biomarkers, likely due to the strong correlation between AVC and subclinical atherosclerosis. The association of AVC with excess cardiovascular mortality beyond coronary atherosclerosis risk merits further investigation.
To assess the utility of dobutamine cardiovascular magnetic resonance (DCMR) results for predicting cardiac events in individuals with reduced left ventricular ejection fraction (LVEF).
It is unknown whether DCMR results identify a poor cardiac prognosis when the resting LVEF is moderately to severely reduced.
Two-hundred consecutive patients aged 30 to 88 (average 64) years with a LVEF ≤55% that were poorly suited for stress echocardiography, underwent DCMR in which LV wall motion score index (WMSI), defined as the average wall motion of the number of segments scored, was assessed at rest, during low dose, and after peak intravenous infusion of dobutamine/atropine. All participants were followed for an average of 5 years after DCMR to ascertain the post testing occurrence of cardiac death, myocardial infarction (MI), and unstable angina or congestive heart failure warranting hospitalization.
After accounting for risk factors associated with coronary arteriosclerosis and MI, a stress induced increase in WMSI during DCMR was associated with future cardiac events (p< 0.001). After accounting for resting LVEF, a DCMR stress induced change in WMSI added significantly to predicting future cardiac events (p=0.003), but this predictive value was confined primarily to those with a LVEF >40%.
In individuals with mild to moderate reductions in LVEF (40% to 55%), dobutamine induced increases in WMSI forecast MI and cardiac death to a greater extent than an assessment of resting LVEF. In those with a LVEF < 40%, a dobutamine induced increase in WMSI does not predict MI and cardiac death beyond the assessment of resting LVEF.
magnetic resonance imaging; cardiac prognosis; myocardial ischemia; dobutamine stress imaging
Genetic variants in myocardial sodium and potassium channel genes are associated with prolonged QT interval and increased risk of sudden death. It is unclear whether these genetic variants remain relevant in subjects with underlying conditions such as diabetes that are associated with prolonged QT interval.
We tested single nucleotide polymorphisms (SNPs) in five candidate genes for association with QT interval in a family-based study of subjects with type 2 diabetes mellitus (T2DM). Thirty-six previously reported SNPs were genotyped in KCNQ1, HERG, SCN5A, KCNE1, and KCNE2 in 901 European Americans from 366 families. The heart rate-corrected (QTc) durations were determined using the Marquette 12SL program. Associations between the QTc interval and the genotypes were evaluated using SOLAR adjusting for age, gender, T2DM status, and body mass index.
Within KCNQ1 there was weak evidence for association between the minor allele of IVS12+14T>C and increased QTc (p=0.02). The minor allele of rs2236609 in KCNE1 trended toward significance with longer QTc (p=0.06), while the minor allele of rs1805123 in HERG trended toward significance with shorter QTc (p=0.07). However, no statistically significant associations were observed between the remaining SNPs and QTc variation.
We found weak evidence of association between three previously-reported SNPs and QTc interval duration. While it appears as though genetic variants in previously identified candidate genes may be associated with QT duration in subjects with diabetes, the clinical implications of these associations in diabetic subjects at high risk for sudden death remains to be determined.
QT interval; diabetes; association study; genetics; ion channels
The purpose of the study was to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM), compared to those with neither condition.
MetS and DM are associated with subclinical atherosclerosis as evidenced by coronary artery calcium (CAC).
The Multiethnic Study of Atherosclerosis included 6,814 African-American, Asian, Caucasian, and Hispanic adults aged 45–84 free of cardiovascular disease at baseline. 5,662 subjects (51% female, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac CT scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%), compared to neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years.
Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals) for incident CAC were 1.7 (1.4–2.0), 1.9 (1.4–2.4), and 1.8 (1.4–2.2) (all p<0.01) and absolute differences in mean progression (volume score) were 7.8 (4.0–11.6; p<0.01), 11.6 (2.7–20.5; p<0.05), and 22.6 (17.2–27.9; p<0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted CHD events in those with MetS without DM (adjusted hazard ratio 4.1, 95% CI=2.0–8.5, p<0.01) and DM (4.9 [1.3–18.4], p<0.05) among those in highest tertile of CAC increase vs. no increase).
Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared to individuals without these conditions, with progression also predicting CHD events in those with MetS and DM.
atherosclerosis; diabetes; risk factors; calcification
Haptoglobin (HP) is an acute phase protein that binds to freely circulating hemoglobin. HP exists as two distinct forms, HP1 and HP2. The longer HP2 form has been associated with cardiovascular (CVD) events and mortality in individuals with type 2 diabetes (T2DM).
This study examined the association of HP genotypes with subclinical CVD, T2DM risk, and associated risk factors in a T2DM-enriched sample. Haptoglobin genotypes were determined in 1208 European Americans (EA) from 473 Diabetes Heart Study (DHS) families via PCR. Three promoter SNPs (rs5467, rs5470, and rs5471) were also genotyped.
Analyses revealed association between HP2-2 duplication and increased carotid intima-media thickness (IMT; p = 0.001). No association between HP and measures of calcified arterial plaque were observed, but the HP polymorphism was associated with triglyceride concentrations (p = 0.005) and CVD mortality (p = 0.04). We found that the HP2-2 genotype was associated with increased T2DM risk with an odds ratio (OR) of 1.49 (95% CI 1.18-1.86, p = 6.59x10-4). Promoter SNPs were not associated with any traits.
This study suggests association between the HP duplication and IMT, triglycerides, CVD mortality, and T2DM in an EA population enriched for T2DM. Lack of association with atherosclerotic calcified plaque likely reflect differences in the pathogenesis of these CVD phenotypes. HP variation may contribute to the heritable risk for CVD complications in T2DM.
Haptoglobin; Genetic polymorphism; Cardiovascular disease; Type 2 diabetes
Monocyte chemoattractant protein-1 (MCP-1) plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD) were assessed in African Americans (AAs) with type 2 diabetes (T2D).
Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and atherosclerotic calcified plaque (CP) in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP.
Participants were 57% female, with mean ± SD (median) age 55.6±9.5 (55.0) years, diabetes duration 10.3±8.2 (8.0) years, urine ACR 149.7±566.7 (14.0) mg/g, CKD-EPI eGFR 92.4±23.3 (92.0) ml/min/1.73m2, MCP-1 262.9±239.1 (224.4) pg/ml, coronary artery CP 280.1±633.8 (13.5), carotid artery CP 47.1±132.9 (0), and aorta CP 1616.0±2864.0 (319.0). Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04) and negatively associated with eGFR (parameter estimate −0.0003, P=0.001). MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes.
Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.
African Americans; Albuminuria; Atherosclerotic calcified plaque; Diabetes; GFR; MCP-1
Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in patients with obesity and type 2 diabetes mellitus (T2DM), and has been associated with the single nucleotide polymorphism (SNP) rs738409 in the PNPLA3 gene. This association remains to be investigated in African Americans with T2DM, a group at lower risk for hepatic steatosis relative to European Americans with T2DM.
We examined 422 African Americans with T2DM (40.3% male; age: 56.4 ± 9.6 years; BMI: 35.2 ± 8.2 kg/m2), all with measures of liver density reflecting hepatic fat content on abdominal computed tomography, and blood glucose and lipid profiles. Associations between rs738409 and phenotypes of interest were determined using SOLAR, assuming an additive model of inheritance with covariates age, sex, BMI and use of lipid-lowering medications.
Mean ± SD liver density was 55.4 ± 10.2 Hounsfield Units. SNP rs738409 in PNPLA3 was significantly associated with liver density (P=0.0075) and hepatic steatosis (P=0.0350), but not with blood glucose, HbA1c, total cholesterol, triglycerides, high-density or low-density lipoprotein levels or liver function tests (P=0.15–0.96).
These findings provide evidence that the PNPLA3 SNP rs738409 contributes to risk for increased liver fat content in African Americans with T2DM, an effect that appears to be independent from serum lipids. Although African Americans are less susceptible to fatty liver than European Americans, PNPLA3 appears to be a risk locus for hepatic steatosis in diabetic African Americans.
type 2 diabetes; genetics; fatty liver disease; African American
Background and Aims
Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5,770 participants (mean age 62 yrs, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.
Methods and Results
Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and young’s modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1-standard deviation (41.91 cm3) increment in Pfat was associated with a 0.00007±0.00002 1/mmHg lower DC (p=0.0002) in men and a 48.1±15.1 mmHg/mm higher YM in women (p=0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.
Higher Pfat is associated with higher carotid stiffness, independent of traditional CVD risk factors and obesity.
pericardial fat; arterial stiffness; distensibility; carotid artery
In diabetes, it remains unclear whether the coronary artery calcium (CAC) score provides additional information about total mortality risk beyond traditional risk factors.
RESEARCH DESIGN AND METHODS
A total of 1,051 participants, aged 34–86 years, in the Diabetes Heart Study (DHS) were followed for 7.4 years. Subjects were separated into five groups using baseline computed tomography scans and CAC scores (0–9, 10–99, 100–299, 300–999, and ≥1,000). Logistic regression was performed adjusting for age, sex, race, smoking, and LDL cholesterol to examine the association between CAC and all-cause mortality. Areas under the curve with and without CAC were compared. Natural splines using continuous measures of CAC were fitted to estimate the relationship between observed CAC and mortality risk.
A total of 17% (178 of 1,051) of participants died during the follow-up. In multivariate analysis, the odds ratios (95% CIs) for all-cause mortality, using CAC 0–9 as the reference group, were CAC 10–99: 1.40 (0.57–3.74); CAC 100–299: 2.87 (1.17–7.77); CAC 300–999: 3.04 (1.32–7.90); and CAC ≥1,000: 6.71 (3.09–16.87). The area under the curve without CAC was 0.68 (95% CI 0.66–0.70), and the area under the curve with CAC was 0.72 (0.70–0.74) (P = 0.0001). Using splines, the estimated risk (95% CI) of mortality for a CAC of 0 was 6.7% (4.6–9.7), and the risk increased nearly linearly, plateauing at CAC ≥1,000 (20.0% [15.7–25.2]).
In diabetes, CAC was shown to be an independent predictor of mortality. Participants with CAC (0–9) were at lower risk (0.9% annual mortality). The risk of mortality increased with increasing levels of CAC, plateauing at approximately CAC ≥1,000 (2.7% annual mortality). More research is warranted to determine the potential utility of CAC scans in diabetes.
A carotid artery calcified plaque (CarCP) linkage peak on chromosome 16p (LOD 4.39 at 8.4cM) in European American (EA) families with type 2 diabetes mellitus (T2DM) from the Diabetes Heart Study (DHS) has been refined by fine-mapping and candidate genes and SNPs evaluated for association with subclinical CVD. Fine-mapping was based on 104 SNPs in 937 subjects from 315 families, including 45 SNPs in six candidate genes (CACNA1H, SEPX1, ABCA3, IL32, SOCS1, and KIAA0350). Linkage and association analyses using variance components analysis (SOLAR; adjusting for age, gender, BMI, and T2DM status) refined the original CarCP linkage into two distinct linkage regions (LOD scores: 3.89 at 6.9cM and 4.86 at 16.0cM). Evidence of linkage for coronary calcified plaque (LOD: 2.27 at 19cM) and a vascular calcification principle component (LOD: 3.71 at 16.0cM) was also observed. The strongest evidence for association with CarCP was observed with SNPs in the A2BP1 gene region (rs4337300 p=0.005) with modest evidence of association with SNPs in CACNA1H (p=0.010–0.033). Bayesian Quantitative Trait Nucleotide analysis identified a SNP, rs1358489, with either a functional effect on CarCP or in linkage disequilibrium with a functional SNP. This study refined the 16p region contributing to vascular calcification. Although the causal variants remain to be identified the results are consistent with a linkage peak which is due to multiple common variants, though rare variants cannot be excluded.
type 2 diabetes; subclinical cardiovascular disease; fine mapping
Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m2) and women (n = 40, BMI = 33.3 ± 4.9 kg/m2) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (−1,160 vs. −647 cm3, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (−104 vs. −298 cm3, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: −43 vs. −88 cm3, P = 0.005; women: −34 vs. −59 cm3, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
To examine whether the relationship between cardiovascular disease risk factors and coronary artery calcification (CAC) is modified by race among those with diabetes.
Data were pooled data from three studies (Multi-Ethnic Study of Atherosclerosis, Family Heart Study, Diabetes Heart Study) for a total of 835 blacks and 1122 whites with diabetes. CAC was quantified by cardiac computed tomography and risk factors were obtained using standard methods. Regression models examined the relationship between risk factors and presence and quantity of CAC.
The average age of the cohort was 60 years; 57% were women. Presence of CAC was lower in blacks compared to whites (odds ratio = 0.22 for men, 0.57 for women, p<0.01). HbA1c, duration of diabetes, LDL, smoking, and BMI were independently associated with presence of CAC; HDL, triglycerides and CRP were not. Race did not modify these associations. Adjustment for multiple risk factors did not explain the race disparity in CAC.
CAC was reduced in blacks compared to whites in persons with diabetes. This effect was most pronounced in men. The relationship between risk factors and CAC did not differ between races. Racial differences in CAC are likely due to unmeasured risk factors and/or genetic susceptibility.
coronary artery disease; diabetes mellitus; epidemiology; African Americans; cohort studies
Pericardial fat has adverse effects on the surrounding vasculature. Previous studies suggest that pericardial fat may contribute to myocardial ischemia in symptomatic individuals. However, it is unknown if pericardial fat has similar effects in asymptomatic individuals.
We determined the association between pericardial fat and myocardial blood flow (MBF) in 214 adults with no prior history of cardiovascular disease from the Minnesota field center of the Multi-Ethnic Study of Atherosclerosis (43% female, 56% Caucasian, 44% Hispanic). Pericardial fat volume was measured by computed tomography. MBF was measured by MRI at rest and during adenosine-induced hyperemia. Myocardial perfusion reserve (PR) was calculated as the ratio of hyperemic to resting MBF.
Gender-stratified analyses revealed significant differences between men and women including less pericardial fat (71.9±31.3 vs. 105.2±57.5 cm3, p<0.0001) and higher resting MBF (1.12±0.23 vs. 0.93±0.19 ml/min/g, p<0.0001), hyperemic MBF (3.49±0.76 vs. 2.65±0.72 ml/min/g, p<0.0001), and PR (3.19±0.78 vs. 2.93±0.89, p = 0.03) in women. Correlations between pericardial fat and clinical and hemodynamic variables were stronger in women. In women only (p = 0.01 for gender interaction) higher pericardial fat was associated with higher resting MBF (p = 0.008). However, this association was attenuated after accounting for body mass index or rate-pressure product. There were no significant associations between pericardial fat and hyperemic MBF or PR after multivariate adjustment in either gender. In logistic regression analyses there was also no association between impaired coronary vasoreactivity, defined as having a PR <2.5, and pericardial fat in men (OR, 1.18; 95% CI, 0.82–1.70) or women (OR, 1.11; 95% CI, 0.68–1.82).
Our data fail to support an independent association between pericardial fat and myocardial perfusion in adults without symptomatic cardiovascular disease. Nevertheless, these findings highlight potentially important differences between asymptomatic and symptomatic individuals with respect to the underlying subclinical disease burden.
Determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness (cIMT) later in life.
Methods and Results
CARDIA is a cohort of 5115 white and black adults who were 18–30 years when they completed a baseline clinic examination in 1985–1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC [score >0 Agatston units (AU) at year 15 or 20], CAC progression (incident CAC at year 20 or an increase in CAC score ≥20 AU), or high cIMT (>80th percentile, year 20). Tea consumption, however, displayed a non-significant trend for an inverse association with CAC (ptrend0.08) and an inverse association with CAC progression (ptrend0.04), but no association with high cIMT (ptrend>0.2). Stratification of the coffee analyses by sex, race, or smoking yielded similar non-significant patterns.
We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC, but not carotid atherosclerosis.
antioxidants; atherosclerosis; carotid arteries; diet; epidemiology; nutrition
Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared coronary artery calcium scores among women randomized to calcium/vitamin D supplementation versus placebo following trial completion.
In an ancillary substudy of women randomized to calcium carbonate (1000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) versus placebo, nested within the Women’s Health Initiative trial of estrogen among women with hysterectomy, we measured CAC with cardiac computed tomography in 754 women aged 50–59 years at randomization. Imaging for CAC was performed at 28 of 40 centers following a mean of 7 years of treatment and scans were read centrally. Coronary artery calcium scores were measured by a central reading center with masking to randomization assignments.
Post-trial CAC measurements were similar in women randomized to calcium/vitamin D supplementation (calcium/D) and those receiving placebo. The mean CAC score was 91.6 for calcium/D and 100.5 for placebo (rank test p-value=0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, ≥10, and ≥100) for calcium/D vs placebo were 0.92 (95% confidence interval, 0.64–1.34), 1.29 (0.88–1.87), and 0.90 (0.56–1.44), respectively. Corresponding odds ratios among women with >50% adherence to study pills and for higher levels of CAC (>300), were similar.
Treatment with moderate doses of calcium plus vitamin D3 did not appear to alter coronary artery calcified plaque burden among postmenopausal women.
calcium; vitamin D; supplementation; coronary artery calcification; coronary heart disease; women’s health
Despite higher rates of nephropathy, calcified atherosclerotic plaque is less prevalent in African Americans with diabetes relative to European Americans. We explored ethnicity-specific relationships between albuminuria and calcified plaque involving the infrarenal aorta, coronary artery, and carotid artery in 835 European American and 393 African American subjects with type 2 diabetes.
RESEARCH DESIGN AND METHODS
Generalized estimating equations with exchangeable correlation and the sandwich estimator of the variance were used to test for association between the principal component of calcified plaque in the three vascular beds and urine albumin-to-creatinine ratio (ACR).
Mean ± SD ages of African American and European American participants were 56.7 ± 9.6 and 61.7 ± 9.1 years, respectively, with diabetes duration of 10.4 ± 7.4 and 10.0 ± 7.3 years and median urine ACR of 17.5 and 13.4 mg/g. In African American and European American participants, respectively, median calcified plaque mass scores were 53.5 and 291 for coronary artery, 3 and 35.5 for carotid artery, and 761 and 3,237 for aorta. With adjustment for age, sex, glomerular filtration rate, and BMI, albuminuria was significantly associated with calcified plaque in European Americans (P = 3.4 × 10−8) but not in African Americans (P = 0.33), with significant ethnic interaction (P = 0.01). Ethnic differences in this relationship persisted after adjustment for blood pressure, smoking, lipids, and use of ACE inhibitors or angiotensin receptor blockers.
Albuminuria is strongly associated with severity of calcified plaque in European Americans with diabetes but not in African Americans. Disparities in this relationship may contribute to ethnic differences in the rates of cardiovascular disease that are observed in subjects with type 2 diabetes.
Carotid intima-media thickness (IMT) is a sub-clinical marker of atherosclerosis and a strong predictor of stroke. Pericardial fat (PF), the fat depot around the heart, has been associated with several atherosclerosis risk factors. We sought to examine the association between carotid IMT and PF, and to examine whether such an association is independent from common atherosclerosis risk factors including measures of overall adiposity.
Unadjusted and multivariable adjusted linear regression analysis was used to examine associations between common (CCA-IMT) and internal (ICA-IMT) carotid IMT with PF in a random sample of 996 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent carotid ultrasound and chest CT at baseline examination.
A significant positive correlation was observed between PF and CCA-IMT (r =0.27, P<0.0001) and ICA-IMT (r =0.17, P<0.0001). In an unadjusted sex-specific linear regression analysis, there was a significant association between PF (1-SD difference) and CCA-IMT (mm) in both women (β coefficient (95% CI): 0.06 (0.04, 0.08), P<0.0001) and men (0.03 (0.01, 0.05), P<0.0002), an association that persisted after further adjusting for age and ethnicity (0.02 (+0.00, 0.04), P=0.0120 for women, and 0.02 (+0.00, 0.03), P=0.0208 for men). However, after additional adjustment for atherosclerosis risk factors and either BMI or waist circumference, these relations were no longer significant in either sex. In similar analyses, PF was significantly associated with ICA-IMT in both men (0.11 (0.06, 0.15), P<0.0001) and women (0.08 (0.02, 0.13), P=041). These relations were no longer significant in women in multivariable adjusted models, but persisted in men in all models except after adjusting for age, ethnicity and waist circumference.
In the general population PF is associated with carotid IMT, an association that possibly not independent from markers of overall adiposity or common atherosclerosis risk factors.
Coronary artery calcified atherosclerotic plaque (CP) is strongly associated with nonsubcutaneous adipose tissue, particularly pericardial adipose tissue (PAT), in community-based studies. We tested for relationships between regional adipose tissue depots and CP in African Americans with longstanding type 2 diabetes. Infrarenal aorta, coronary, and carotid artery CP and pericardial, visceral, intermuscular, and subcutaneous organ-specific adipose tissue volumes were measured using single and multidetector computed tomography (CT) in 422 African Americans with type 2 diabetes. Generalized estimating equations using exchangeable correlation and the sandwich estimator of the variance were used to test for associations between CP and adipose tissue depots. Mean (s.d.) age was 56.5 (7.6) years, diabetes duration 10.3 (7.6) years, PAT 85.3 (36.1) cm3/45 mm and visceral adipose tissue (VAT) 174.9 (70.1) cm3/15 mm. Adjusting for age, gender, BMI, blood pressure, medications, proteinuria, smoking, lipids, and 25-hydroxyvitamin D, PAT was positively associated with the presence (P = 0.009) and quantity of coronary artery CP in African Americans (P = 0.004), as well as the quantity of infrarenal aorta CP (P = 0.004). As in European Americans, PAT is associated with CP in African Americans with type 2 diabetes. Ethnic differences in the relationships between organ-specific adipose tissue depots and atherosclerosis require further study.
Cardiac CT scans for the assessment of coronary calcium scores include approximately 70% of the lung volume and may be useful for the quantitative assessment of emphysema. The reproducibility of lung density measures from cardiac CTs and their validity compared to lung density measures from full-lung scans is unknown.
Methods and Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) performed paired cardiac CT scans for 6,814 participants at baseline and at follow-up. The MESA-Lung Study assessed lung density measures in the lung fields of these cardiac scans, counting voxels below -910 HU as moderate-to-severe emphysema-like lung regions. We evaluated: 1) the reproducibility of lung density measures among 120 randomly selected participants, 2) the comparability of measures acquired on electron-beam CT (EBT) and multidetector CT (MDCT) scanners among 10 participants; and 3) the validity of these measures compared to full-lung scans among 42 participants. Limits of agreement were determined using Bland-Altman approaches.
Percent emphysema measures from paired cardiac scans were highly correlated (r=0.92-0.95) with mean difference of -0.05% (95% limits of agreement: -8.3, 8.4%). Measures from EBT and MDCT scanners were comparable (mean difference -0.9%; 95% limits of agreement: -5.1, 3.3%). Percent emphysema measures from MDCT cardiac and MDCT full-lung scans were highly correlated (r=0.93) and demonstrated reasonable agreement (mean difference 2.2%; 95% limits of agreement: -9.2, 13.8%).
While full-lung imaging is preferred for the quantification of emphysema, the lung imaging from paired cardiac CTs provided a reproducible and valid quantitative assessment of emphysema in a population-based sample.
Cardiac computed tomography (CT) is a well-established tool for the detection of cardiovascular calcium. Coronary artery calcification (CAC) is highly sensitive for the detection of coronary artery disease (CAD) as well as predictive of future cardiovascular (CV) events. Descending thoracic aortic calcification (DTAC) is common in the elderly and its presence is also associated with increased risk of CV events. Previous studies demonstrate that DTAC is associated with obstructive CAD and coronary risk factors. However, no prior studies have examined the association of CAC and DTAC as detected by cardiac CT in a large population-based cohort.
In the Multi-Ethnic Study of Atherosclerosis, the study population included a population based sample of four ethnic groups (Chinese, White, Hispanic and African-American) of 6814 women and men ages 45−84 years old. Participants underwent non-enhanced cardiac CT and both CAC and DTAC were quantified. DTAC was measured from the lower edge of the pulmonary artery bifurcation to the cardiac apex. Multivariable relative risk regression was used to evaluate relationships between CAC, DTAC and measured cardiovascular risk factors.
Overall 3030 (44%) did not demonstrate any detectable CAC or DTAC. A total of 1930 (28%) had only CAC, 386 (6%) had isolated DTAC, and 1464 (22%) participants were found to have both CAC and DTAC. CAC had a higher prevalence than DTAC in men (58% vs. 45%). Participants with DTAC were older than those with CAC (mean age was 71 and 66 years old, respectively). Participants with DTAC had increased risk for the presence of CAC independent of cardiovascular risk factors (prevalence ratio [PR]; 1.17 95% CI 1.07−1.28). Severity of DTAC was a stronger predictor of the presence of CAC in women as compared to men (PR; 1.04 95% CI 1.02 −1.06, and PR; 0.99 95% CI 0.98− 1.01, respectively).
DTAC was found to be a strong predictor of CAC independent of CV risk factors. Ongoing follow-up of this cohort will evaluate whether DTAC is an independent marker of risk for CV events.
Aims. Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. We hypothesize that polymorphisms in ALOX12, ALOX15, ALOX5, and ALOX5AP genes are associated with subclinical atherosclerosis in multiple vascular beds. Methods. Families with two or more siblings with type 2 diabetes and their nondiabetic siblings were studied as part of the Diabetes Heart Study (DHS). European American diabetic (n = 828) and nondiabetic (n = 170) siblings were genotyped for SNPs in the ALOX12, ALOX15, ALOX5, and ALOX5AP genes. Subclinical measures of atherosclerosis (IMT, coronary (CorCP), carotid (CarCP) and aortic (AorCP) calcified plaque) were obtained. Results. Associations were observed between ALOX12 with CorCP, ALOX5 with CorCP, AorCP, and IMT, and ALOX5AP with CorCP and CarCP, independent of known epidemiologic risk factors. Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP).
Conclusions. Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes. These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease.
High x-ray radiation dose is a major public concern with the increasing use of multidetector computed tomography (CT) for diagnosis of cardiovascular diseases. This issue must be effectively addressed by dose-reduction techniques. Recently, our group proved that an internal region of interest (ROI) can be exactly reconstructed solely from localized projections if a small subregion within the ROI is known. In this article, we propose to use attenuation values of the blood in aorta and vertebral bone to serve as the known information for localized cardiac CT. First, we describe a novel interior tomography approach that backprojects differential fan-beam or parallel-beam projections to obtain the Hilbert transform and then reconstructs the original image in an ROI using the iterative projection onto convex sets algorithm. Then, we develop a numerical phantom based on clinical cardiac CT images for simulations. Our results demonstrate that it is feasible to use practical prior information and exactly reconstruct cardiovascular structures only from projection data along x-ray paths through the ROI.
computed tomography; cardiac CT; local reconstruction; fan-beam reconstruction; parallel-beam reconstruction; radiation dose reduction