Left ventricular aneurysm versus pseudoaneurysm: Diagnosis in the era of multi-modality imaging and 3D-printing.

In this case report, we illustrate the contemporary use of multi-modality cardiac imaging and three-dimensional (3D)-printing in the diagnosis and precise surgical planning of a large ventricular aneurysm with an extensive thrombus burden after myocardial infarction. We further discuss an integrated multimodality approach in the evaluation of ventricular outpouchings.

Effects of supplemental oxygen on cardiovascular magnetic resonance water proton relaxation time constant measurements (T1, T2 and T2*).

OBJECTIVE: To study, the effects of supplemental oxygen on the measurement of native cardiovascular water proton relaxation time constants using commercially available protocols. METHODS: T1, T2 and T2* relaxation time constant mapping were performed in twelve volunteers at 1.5 T breathing room air and supplemental oxygen supplied by nasal cannula and a non-rebreather mask. Regions-of-interest were drawn for quantitative measurements in the bloodpool of each ventricle and atria as well as septal myocardium. The effects of supplemental oxygen were investigated statistically using a mixed model analysis of variance. Intra- and inter-observer reproducibility were assessed using the Intraclass Correlation Coefficient and Coefficient of Variation. RESULTS: Blood T1 relaxation time constants in the left ventricle (T1 change = -241.0 ms) and left atrium (T1 change = -247.0 ms) decreased significantly in every subject after oxygen inhalation with a non-rebreather mask (p < 0.001). No significant changes of T1 in the right side of the heart were detected after oxygen inhalation with the non-rebreather mask (p = 0.345). Oxygen inhalation with nasal cannula did not significantly change blood T1 in the study (p = 0.497). No significant changes in myocardial T1 (p = 0.390), T2 (p = 0.960) or T2* (p = 0.438) were observed with supplemental oxygen supplied by nasal cannula or the non-rebreather mask. Results were similar in mid-short-axis and horizontal long-axis acquisitions. CONCLUSION: Supplemental oxygen does not affect myocardial relaxation time constant measurements with current protocols. On the other hand, blood T1 measurements with the inhalation of supplemental oxygen supplied by a non-rebreather mask change significantly and could affect myocardial tissue characterization if used for the calculation of extracellular volume. Additionally, current relaxation time constant mapping protocols do not reproducibly detect myocardial T1 changes with supplemental oxygen inhalation.

Prolonged central circulation transit time in patients with HFpEF and HFrEF by magnetic resonance imaging.

Aims: Prolonged central circulation transit time (TT) has long been associated with heart failure (HF) and left ventricular (LV) dysfunction. In this study, we assessed the central circulation TT using cardiovascular magnetic resonance imaging (CMR) in patients with HF of preserved ejection fraction (HFpEF) and of reduced EF (HFrEF) and investigated its relation to haemodynamics. Methods and results: Fifty eight prospectively recruited volunteers underwent CMR. TT was taken as the time between the peaks of time-intensity curves from first pass perfusion images and normalized to cardiac cycle length intervals. Left ventricular ejection fraction was 55 ± 3%, 57 ± 7%, and 28 ± 10% in control (N = 10), HFpEF (N = 20), and HFrEF (N = 28), respectively (P < 0.001). Global central TT from right atrium to ascending aorta was significantly prolonged in patients with HFrEF [17 ± 5 cardiac cycles (cc)] and HFpEF (12 ± 3 cc) when compared to the normal controls (8 ± 1 cc) (P < 0.001). Regional TT was also prolonged in HF patients between right atrium and pulmonary artery (PA), PA and left atrium (LA), and LA and ascending aorta (all P-value < 0.001) with the longest delay seen between PA and LA. Among 48 HF patients, 28 underwent same day cardiac catheterization. Multivariate regression analysis suggested while reduced left and right ventricular EF were the strongest correlates for HFrEF increased pulmonary capillary wedge (PCWP) and reduced PA oxygen saturation were the strongest correlates for HFpEF. Conclusions: Global and regional central TT can be assessed in the first pass perfusion imaging. Prolonged normalized global TT correlates with reduced EF in HFrEF and increased PCWP in HFpEF.

Self-calibrated correlation imaging with k-space variant correlation functions.

PURPOSE: Correlation imaging is a previously developed high-speed MRI framework that converts parallel imaging reconstruction into the estimate of correlation functions. The presented work aims to demonstrate this framework can provide a speed gain over parallel imaging by estimating k-space variant correlation functions. METHODS: Because of Fourier encoding with gradients, outer k-space data contain higher spatial-frequency image components arising primarily from tissue boundaries. As a result of tissue-boundary sparsity in the human anatomy, neighboring k-space data correlation varies from the central to the outer k-space. By estimating k-space variant correlation functions with an iterative self-calibration method, correlation imaging can benefit from neighboring k-space data correlation associated with both coil sensitivity encoding and tissue-boundary sparsity, thereby providing a speed gain over parallel imaging that relies only on coil sensitivity encoding. This new approach is investigated in brain imaging and free-breathing neonatal cardiac imaging. RESULTS: Correlation imaging performs better than existing parallel imaging techniques in simulated brain imaging acceleration experiments. The higher speed enables real-time data acquisition for neonatal cardiac imaging in which physiological motion is fast and non-periodic. CONCLUSION: With k-space variant correlation functions, correlation imaging gives a higher speed than parallel imaging and offers the potential to image physiological motion in real-time. Magn Reson Med 79:1483-1494, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical outcomes with or without statin therapy: The St Francis Heart Study.

BACKGROUND AND AIMS: The efficacy of statin therapy remains unknown in patients eligible for statin therapy with and without elevated coronary calcium score (CAC). The study sought to evaluate how cardiovascular risk factors, expressed in terms of statin eligibility for primary prevention, and CAC modify clinical outcomes with and without statin therapy. METHODS: We conducted a post-hoc analysis of the St. Francis Heart Study treatment trial, a double-blind, placebo-controlled randomized controlled trial of atorvastatin (20 mg), vitamin C (1 g), and vitamin E (1000 U) daily, versus placebos in 990 asymptomatic individuals with CAC ≥ 80th percentile for age and gender. Primary cardiovascular outcomes included non-fatal myocardial infarction or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. We further stratified the treatment and placebo groups by eligibility (eligible when statin indicated) for statin therapy based on 2013 ACC/AHA guidelines and based on CAC categories. RESULTS: After a median follow-up of 4.8 years, cardiovascular events had occurred in 3.9% of the statin treated but not eligible, 4.6% of the untreated and not eligible, 8.9% of the treated and eligible and 13.4% of the untreated and eligible groups, respectively (p<0.001). Low CAC (<100) occurred infrequently in statin eligible subjects (≤4%) and was associated with low 10-year event rate (<1 per 100 person-years). In contrast, high CAC (>300) occurred frequently in more than 35% of the statin not eligible subjects and was associated with a high 10-year event rate (≥17 per 100 person-years). Risk prediction improved significantly when both clinical risk profile and CAC score were combined (net reclassification index p = 0.002). CONCLUSIONS: Under the current statin treatment guidelines a small number of statin eligible subjects with low CAC might not benefit from statin therapy within 5 years. However, the statin not eligible subjects with high CAC have high event rate attributing to loss of opportunity for effective primary prevention.

CTA Detection of Left Atrial Stasis and Thrombus in Patients with Atrial Fibrillation.

BACKGROUND: We investigated computed tomography (CT) angiography (CTA) in assessment of left atrial appendage (LAA) stasis and thrombus in preprocedural evaluation for atrial fibrillation (AF) ablation in a large community cohort. METHODS AND RESULTS: We reviewed CTA and transesophageal echocardiographic images obtained in 861 consecutive patients with a history of AF undergoing same-day CTA and transesophageal echocardiogram (TEE) before AF ablation at a single hospital (2006-2013). CTA findings of LAA filling defects from acquisitions without electrocardiogram gating were compared to TEE features of LAA stasis (grade 0-4) and thrombus. Stasis grade 0 or 1 by TEE in the absence of thrombus was defined as a negative result. In addition, LAA peak flow velocity was assessed by TEE. Average age was 61 ± 10 years and 75% were male. On CTA, 161 patients (19%) had LAA filling defects on CTA and 21 had ≥grade 2 stasis on TEE, including two with thrombus, resulting in a positive predictive value of only 13%. However, among 670 CTA-negative patients, 669 (99%) were negative for thrombus or stasis by TEE with one false-negative CTA in a patient with grade 2 stasis by TEE but no thrombus, yielding a negative predictive value of 99.9%. Slow LAA Doppler flow velocity was the most important determinant of false-positive CTA results in multivariate analysis (P < 0.0001) CONCLUSION: LAA filling defects on CT are associated with slow LAA flow velocity. AF patients without LAA filing defects on CT are free of significant stasis and thrombus on TEE. It may be possible to eliminate TEE in up to 80% of AF ablation patients based on negative CTA findings.

Midlife Cardiovascular Risk Factors and Late-Life Unrecognized and Recognized Myocardial Infarction Detect by Cardiac Magnetic Resonance: ICELAND-MI, the AGES-Reykjavik Study.

BACKGROUND: Associations of atherosclerosis risk factors with unrecognized myocardial infarction (UMI) are unclear. We investigated associations of midlife risk factors with UMI and recognized MI (RMI) detected 31 years later by cardiac magnetic resonance. METHODS AND RESULTS: The Reykjavik Study (1967-1991) collected serial risk factors in subjects, mean (SD) age 48 (7) years. In ICELAND-MI (2004-2007), 936 survivors (76 (5) years) were evaluated by cardiac magnetic resonance. Analysis included logistic regression and random effects modeling. Comparisons are relative to subjects without MI. At baseline midlife evaluation, a modified Framingham risk score was significantly higher in RMI and in UMI versus no MI (7.4 (6.3)%; 7.1 (6.2)% versus 5.4 (5.8)%, P<0.001). RMI and UMI were more frequent in men (65%, 64% versus 43%; P<0.0001). Baseline systolic and diastolic blood pressure were significantly higher in UMI (138 (17) mm Hg versus 133 (17) mm Hg; P<0.006; 87 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Diastolic BP was significantly higher in RMI (88 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Cholesterol and triglycerides were significantly higher in RMI (6.7 (1.1) mmol/L versus 6.2 (1.1) mmol/L; P=0.0005; and 1.4 (0.7) mmol/L versus 1.1 (0.7) mmol/L; P<0.003). Cholesterol trended higher in UMI (P=0.08). Serial midlife systolic BP was significantly higher in UMI versus no MI (ß [SE] = 2.69 [1.28] mm Hg, P=0.04). Serial systolic and diastolic BP were significantly higher in RMI versus no MI (4.12 [1.60] mm Hg, P=0.01 and 2.05 [0.91] mm Hg, P=0.03) as were cholesterol (0.43 [0.11] mmol/L, P=0.0001) and triglycerides (0.3 [0.06] mmol/L, P<0.0001). CONCLUSIONS: Midlife vascular risk factors are associated with UMI and RMI detected by cardiac magnetic resonance 31 years later. Systolic blood pressure was the most significant modifiable risk factor associated with later UMI.

Cardiac imaging for assessment of left atrial appendage stasis and thrombosis.

Atrial fibrillation (AF) is the most-common arrhythmia in the elderly population (age >65 years). The left atrial appendage (LAA) is the main location of thrombus formation, predominantly in patients with nonvalvular AF. This Review is focused on the pathophysiology, assessment, and clinical implications of stasis (or spontaneous echocardiographic contrast; SEC) and thrombus formation in the LAA. The gold-standard modality for assessment of SEC and thrombus in the LAA is echocardiography, particularly transoesophageal echocardiography (TEE). Cardiac CT (CCT) is an accurate, noninvasive alternative to TEE for the detection of LAA thrombi, distinctly when delayed-imaging acquisition protocols are used. Prospective studies to validate the use of cardiac MRI (CMR) for this purpose are needed, and will avoid the need for radiation and iodinated contrast. CCT or CMR could potentially be implemented to rule out LAA thrombus, avoiding unnecessary preprocedural TEE. Cardiac imaging is also of primary importance in the setting of LAA closure devices and electrophysiological studies. New trials are needed to compare the various imaging modalities, with surgicopathological findings as a reference standard.

Relationship of phasic left atrial volume and emptying function to left ventricular filling pressure: a cardiovascular magnetic resonance study.

BACKGROUND: Left atrial volume (LAV) and emptying fraction (LAEF) are phasic during cardiac cycle. Their relationships to left ventricular end diastolic pressure (LVEDP) have not been fully defined. METHODS: Forty one patients undergoing clinically indicated left heart catheterization were recruited for same day cardiovascular magnetic resonance (CMR). LAV and LAEF were assessed in cine images using biplane area and length method. Three phasic LAV was assessed at LV end systole (LAV(max)), LV end diastole (LAV(min)) and late LV diastole prior to LA contraction (LAV(ac)). LAEF was assessed as global LAEF (LAEF(Total)), passive (LAEF(Passive)) and active LAEF (LAEF(Contractile)). The relationships of phasic LAV and LAEF to LVEDP were assessed using Receiver operating characteristic comparing areas under the curves (AUC). RESULTS: The mean age of the patients was 59 years. A history of heart failure was present in 16 (39%) with NYHA functional class III or IV in 8 (20%) patients. Average LV ejection fraction was 49 ± 16% ranging from 10% to 74% and LVEDP by catheterization 14 ± 8 mmHg ranging from 4 mmHg to 32 mmHg. LAV(min) had the strongest association with LVEDP elevation (>12 mmHg) (AUC 0.765, p = 0.002), as compared to LAV(max) (AUC 0.677, p = 0.074) and LAV(ac) (AUC 0.735, p = 0.008). Among three phasic LAEF assessed, LAEF(Total) had the closest association with LVEDP elevation (AUC 0.780, p = 0.001), followed by LAEF(Contractile) (AUC 0.698, p = 0.022) and LAEF(Passive) (AUC 0.656, p = 0.077). CONCLUSIONS: Increased LAV(min) and decreased LAEF(Total) have the best performance in identifying elevated LVEDP among three phasic LAV and LAEF analyzed. Future studies should further characterize LA phasic indices in clinical outcomes.

Effects of hemodynamics on global and regional lung perfusion: a quantitative lung perfusion study by magnetic resonance imaging.

BACKGROUND: Cardiac hemodynamics affect pulmonary vascular pressure and flow, but little is known of the effects of hemodynamics on lung perfusion at the tissue level. We sought to investigate the relationship between hemodynamic abnormalities in patients with left heart failure and global and regional lung perfusion using lung perfusion quantification by magnetic resonance imaging. METHODS AND RESULTS: Lung perfusion was quantified in 10 normal subjects and 28 patients undergoing clinically indicated left and right heart catheterization and same day research cardiac magnetic resonance imaging. A total of 228 lung slices were evaluated. Global lung perfusion, determined as the average of 6 coronal lung slices through the anterior, mid, and posterior left and right lungs, was significantly lower in patients with reduced cardiac index (<2.5 L/min per m(2)): 94±30 mL/100 mL per minute versus 132±40 mL/100 mL per minute in those with preserved cardiac index (≥2.5 L/min per m(2); P=0.003). The gravitational anterior to posterior perfusion gradient was inversely associated with left ventricular end-diastolic pressure (r=-0.728; P<0.001), resulting in a blunted perfusion gradient in patients with elevated left ventricular end-diastolic pressure, a finding largely attributed to the perfusion reduction in posterior lung regions. In a multivariate regression analysis adjusting for all hemodynamic variables, altered lung perfusion gradient was most closely associated with increased mean pulmonary arterial pressure (P=0.016). CONCLUSIONS: Increased left ventricular filling pressure and the resultant increase in pulmonary arterial pressure are associated with disruption of the normal gravitational lung perfusion gradient. Our findings underscore the complexity of heart-lung interaction in determining pulmonary hemodynamics in left heart failure.

Prevalence and prognosis of unrecognized myocardial infarction determined by cardiac magnetic resonance in older adults.

CONTEXT: Unrecognized myocardial infarction (MI) is prognostically important. Electrocardiography (ECG) has limited sensitivity for detecting unrecognized MI (UMI). OBJECTIVE: Determine prevalence and mortality risk for UMI detected by cardiac magnetic resonance (CMR) imaging or ECG among older individuals. DESIGN, SETTING, AND PARTICIPANTS: ICELAND MI is a cohort substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study (enrollment January 2004-January 2007) using ECG or CMR to detect UMI. From a community-dwelling cohort of older individuals in Iceland, data for 936 participants aged 67 to 93 years were analyzed, including 670 who were randomly selected and 266 with diabetes. MAIN OUTCOME MEASURES: Prevalence and mortality of MI through September 1, 2011. Results reported with 95% confidence limits and net reclassification improvement (NRI). RESULTS: Of 936 participants, 91 had recognized MI (RMI) (9.7%; 95% CI, 8% to 12%), and 157 had UMI detected by CMR (17%; 95% CI, 14% to 19%), which was more prevalent than the 46 UMI detected by ECG (5%; 95% CI, 4% to 6%; P < .001). Participants with diabetes (n = 337) had more UMI detected by CMR than by ECG (n = 72; 21%; 95% CI, 17% to 26%, vs n = 15; 4%; 95% CI, 2% to 7%; P < .001). Unrecognized MI by CMR was associated with atherosclerosis risk factors, coronary calcium, coronary revascularization, and peripheral vascular disease. Over a median of 6.4 years, 30 of 91 participants (33%; 95% CI, 23% to 43%) with RMI died, and 44 of 157 participants (28%; 95% CI, 21% to 35%) with UMI died, both higher rates than the 119 of 688 participants (17%; 95% CI, 15% to 20%) with no MI who died. Unrecognized MI by CMR improved risk stratification for mortality over RMI (NRI, 0.34; 95% CI, 0.16 to 0.53). Adjusting for age, sex, diabetes, and RMI, UMI by CMR remained associated with mortality (hazard ratio [HR], 1.45; 95% CI, 1.02 to 2.06, absolute risk increase [ARI], 8%) and significantly improved risk stratification for mortality (NRI, 0.16; 95% CI, 0.01 to 0.31), but UMI by ECG did not (HR, 0.88; 95% CI, 0.45 to 1.73; ARI, -2%; NRI, -0.05; 95% CI, -0.17 to 0.05). Compared with those with RMI, participants with UMI by CMR used cardiac medications such as statins less often (36%; 95% CI, 28% to 43%, or 56/157, vs 73%; 95% CI, 63% to 82%, or 66/91; P < .001). CONCLUSIONS: In a community-based cohort of older individuals, the prevalence of UMI by CMR was higher than the prevalence of RMI and was associated with increased mortality risk. In contrast, UMI by ECG prevalence was lower than that of RMI and was not associated with increased mortality risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01322568.

Effects of respiratory cycle and body position on quantitative pulmonary perfusion by MRI.

PURPOSE: To evaluate the performance of lung perfusion imaging using two-dimensional (2D) first pass perfusion MRI and a quantitation program based on model-independent deconvolution algorithm. MATERIALS AND METHODS: In eight healthy volunteers 2D first pass lung perfusion was imaged in coronal planes using a partial Fourier saturation recovery stead state free precession (SSFP) technique with a temporal resolution of 160 ms per slice acquisition. The dynamic signal in the lung was measured over time and absolute perfusion calculated based on a model-independent deconvolution program. RESULTS: In the supine position mean pulmonary perfusion was 287 ± 106 mL/min/100 mL during held expiration. It was significantly reduced to 129 ± 68 mL/min/100 mL during held inspiration. Similar differences due to respiration were observed in prone position with lung perfusion much greater during expiration than during inspiration (271 ± 101 versus 99 ± 38 mL/min/100 mL (P < 0.01)). There was a linear increase in pulmonary perfusion from anterior to posterior lung fields in supine position. The perfusion gradient reversed in the prone position with the highest perfusion in anterior lung and the lowest in posterior lung fields. CONCLUSION: Lung perfusion imaging using a 2D saturation recovery SSFP perfusion MRI coupled with a model-independent deconvolution algorithm demonstrated physiologically consistent dynamic heterogeneity of lung perfusion distribution.

Left ventricular filling pressure assessment using left atrial transit time by cardiac magnetic resonance imaging.

BACKGROUND: Left atrial (LA) size and function reflect left ventricular (LV) hemodynamics. In the present study, we developed a novel method to determine LA circulation transit time (LATT) by MRI and demonstrated its close association with LV filling pressure. METHODS AND RESULTS: All subjects were prospectively recruited and underwent contrast-enhanced MR dynamic imaging. Mean LATT was determined as the time for contrast to transit through the LA during the first pass. In an invasive study group undergoing clinically indicated cardiac catheterization (n=25), LATT normalized by R-R interval (nLATT) was closely associated with LV early diastolic pressure (r=0.850, P=0.001), LV end-diastolic pressure (r=0.910, P<0.001), and mean diastolic pressure (r=0.912, P<0.001). In a larger noninvasive group (n=56), nLATT was prolonged in patients with LV systolic dysfunction (n=47) (10.1±3.0 versus 6.6±0.7 cardiac cycles in normal control subjects, n=9; P<0.001). Using a linear regression equation derived from the invasive group, noninvasive subjects were divided into 3 subgroups by estimated LV end-diastolic pressure: ≤10 mm Hg, 11 to 14 mm Hg, and ≥15 mm Hg. There were graded increases from low to high LV end-diastolic pressure subgroups in echocardiographic mitral medial E/e' ratio: 9±5, 11±4, and 13±3 (P=0.023); in B-type natriuretic peptide (interquartile range): 44 (60) pg/mL, 87 (359) pg/mL, and 371 (926) pg/mL (P=0.002); and in N-terminal pro-B-type natriuretic peptide: 57 (163) pg/mL, 208 (990) pg/mL, and 931 (1726) pg/mL (P=0.002), demonstrating the ability of nLATT to assess hemodynamic status. CONCLUSIONS: nLATT by cardiac MR is a promising new parameter of LV filling pressure that may provide graded noninvasive hemodynamic assessment.

Cystatin C, albuminuria, and mortality among older adults with diabetes.

OBJECTIVE: Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health outcomes among individuals with diabetes. Joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population. RESEARCH DESIGN AND METHODS: This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples. RESULTS: Of 691 participants, 378 died over 10 years of follow-up. Cystatin C-estimated GFR <60 ml/min per 1.73 m(2), creatinine-based estimated GFR <60 ml/min per 1.73 m(2), and urine ACR > or =30 mg/g were each associated with increased mortality risk with hazard ratios of 1.73 (95% CI 1.37-2.18), 1.54 (1.21-1.97), and 1.73 (1.39-2.17), respectively, adjusting for age, sex, race, diabetes duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol, lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent heart failure. Cystatin C-estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C-estimated GFR predicted mortality more strongly than creatinine-based estimated GFR. CONCLUSIONS: Albuminuria and impaired GFR were independent, additive risk factors for mortality among older adults with diabetes. These findings support current recommendations to regularly assess both albuminuria and GFR in the clinical care of patients with diabetes; a focus on interventions to prevent or treat CVD in the presence of albuminuria, impaired GFR, or both; and further consideration of cystatin C use in clinical care.

Cardiovascular and mortality risk prediction and stratification using urinary albumin excretion in older adults ages 68-102: the Cardiovascular Health Study.

BACKGROUND: Elevated urinary albumin excretion (UAE) is associated with the risk of cardiovascular disease (CVD) and all-cause mortality. We tested the hypothesis that elevated UAE improves cardiovascular risk stratification in an elderly cohort aged 68-102 years. METHODS: We evaluated UAE in 3112 participants of the Cardiovascular Health Study who attended the 1996-1997 examination and had median follow up of 5.4 years. Elevated UAE was defined as urinary albumin to creatinine ratio > or =30 microg/mg. Microalbuminuria and macroalbuminuria were defined as urinary albumin to creatinine ratio 30-300 microg/mg and >300 microg/mg, respectively. Outcomes included CVD (myocardial infarction, stroke, cardiovascular death) and all-cause mortality. Cox proportional hazards models were used to assess the risk of outcomes associated with elevated UAE. RESULTS: The prevalence of elevated UAE was 14.3%, 17.1% and 26.9% in those aged 68-74, 75-84 and 85-102 years, respectively. CVD incidence and all-cause mortality were doubled (7.2% and 8.1% per year) in those with microalbuminuria and tripled (11.1% and 12.3% per year) in those with macroalbuminuria compared to those with normal UAE (3.3% and 3.8% per year). The increased CVD and mortality risks were observed in all age groups after adjustment for conventional risk factors. The adjusted population attributable risk percent of CVD and all-cause mortality for elevated UAE was 11% and 12%, respectively. When participants were cross-classified by UAE and Framingham Risk Score categories, the 5-year cumulative incidence of coronary heart disease among participants with elevated UAE and a 5-year predicted risk of 5-10% was 20%, substantially higher than 6.3% in those with UAE <30m microg/mg. CONCLUSION: Elevated UAE was associated with an increased risk of CVD and all-cause mortality in all age groups from 68 to 102 years. Combining elevated UAE with the Framingham risk scores may improve risk stratification for CVD in the elderly.

Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.

BACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction. METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72% (95% CI, 1.46 to 2.01) increased risk for CVD death and a 52% (95% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54% for CVD death and 79% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic. CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: the Cardiovascular Health Study.

PURPOSE: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events. METHODS: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >or=65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33%), those with hypertension (52%) and those with diabetes, with or without hypertension (15%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass. RESULTS: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95% CI 1.08, 2.30]) or diabetes (OR 2.51 [95% CI 1.27, 4.94]). CONCLUSION: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease.