Coronary artery calcium and cardiovascular disease prediction by scanner type: the multi-ethnic study of atherosclerosis.

AIM: To evaluate the predictive value of coronary artery calcium (CAC) scoring methods across cardiac computed tomography (CT) scanner types. MATERIALS AND METHODS: CAC was measured in participants from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of participants free of baseline cardiovascular disease (CVD), using either EBCT (electron beam CT) or MDCT (multidetector CT). The risks for incident coronary heart disease (CHD) and CVD events were compared for CAC scores per SD using Cox proportional hazards models with multivariable adjustment in 3,362 MESA participants with detectable CAC. RESULTS: Using the Agatston score, the hazard ratio (HR) and 95% confidence interval (CI) for CHD was 1.50 (1.27,1.78) for EBCT and 1.60 (1.37,1.87) for MDCT. Using volume and density scores, the HR for CHD was 2.14 (1.71,2.68) for volume and 0.61 (0.48,0.76) for density on EBCT and 1.73 (1.42,2.11) for volume and 0.88 (0.71,1.10) for density on MDCT. Similar results were seen for CVD risk and in analyses stratified by sex, body mass index (BMI), and age. The volume and density score model demonstrated higher areas under the curve (AUC) for CHD than the Agatston score with EBCT (0.702, 95% CI: 0.666,0.738 versus 0.677, 95% CI: 0.638,0.715, p<0.001) and MDCT (0.669, 95% CI: 0.632,0.705 versus 0.660, 95% CI: 0.622,0.697, p=0.216). CONCLUSION: The CAC volume and density scores provide better risk prediction than the Agatston score for CHD and CVD events, regardless of CT scanner type. CAC density was strongly and inversely associated with CHD risk. Both density and volume score prediction were stronger for EBCT than MDCT.

Adipokines are associated with lower extremity venous disease: the San Diego population study.

BACKGROUND: Obesity is a risk factor for venous disease. We tested the associations between adipokines and the presence and severity of venous disease. METHODS: Participants for this analysis were drawn from a cohort of 2408 employees and retirees of a university in San Diego who were examined for venous disease using duplex ultrasonography. From this cohort, a case-control study sample of all 352 subjects with venous disease and 352 age-, sex- and race-matched subjects without venous disease were included in this analysis. All subjects completed health history questionnaires, had a physical examination with anthropometric measurements and had venous blood analyzed for adipokines. RESULTS: After adjustment for age, sex and race, those with venous disease had significantly higher levels of body mass index (BMI), leptin and interleukin-6. Levels of resistin and tumor necrosis factor-alpha were also higher but of borderline significance (0.05 < P < 0.10). Compared with the lowest tertile and with adjustment for age, sex, race and BMI, the 2nd and 3rd tertiles of resistin (odds ratios, 1.9 and 1.7, respectively), leptin (1.7 and 1.7) and tumor necrosis factor-alpha (1.4 and 1.7) were associated with increasing severity of venous disease. Conversely, a 5 kg m⁻² increment in BMI was associated with a higher odds ratio (1.5) for venous disease, which was independent of the adipokines included in this study. CONCLUSIONS: Both obesity and adipokines are significantly associated with venous disease. These associations appear to be independent of each other, suggesting potentially different pathways to venous disease.

Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study.

BACKGROUND: Clinically silent deep vein thrombosis (DVT) is common and may cause chronic venous disease that resembles post-thrombotic syndrome. OBJECTIVE: We evaluated whether peripheral venous disease in a general population shares risk factors with DVT. METHODS: In an established cohort of 2404 men and women, the San Diego Population Study, peripheral venous disease was evaluated using physical examination, symptom assessment and venous ultrasound. We performed a case-control study including 308 cases in four hierarchical groups by severity and 346 controls without venous abnormalities, frequency matched to cases by 10-year age group, race and gender. Cases and controls had no prior history of venous thrombosis. Hemostatic risk factors were measured in cases and controls. RESULTS: Accounting for age, obesity and family history of leg ulcer, odds ratios (ORs) of venous disease for elevated factor VIII, von Willebrand factor (VWF), D-dimer and for factor V Leiden were 1.4 (95% CI 0.9-2.1), 1.5 (CI 1.0-2.3), 1.7 (CI 1.1-2.8) and 1.1 (CI 0.5-2.4), respectively. These associations were larger for the two most severe case groups; ORs 2.0 (CI 1.0-3.8), 1.7 (CI 0.9-3.3), 2.7 (CI 1.2-6.1) and 2.3 (CI 0.8-7.1). Each hemostatic factor was also associated with severity of venous disease, for example elevated D-dimer was associated with a 2.2-fold increased odds of being in one higher severity case group. Prothrombin 20210A was not associated with venous disease. CONCLUSIONS: DVT risk factors are associated with presence and severity of peripheral venous disease. Results support a hypothesis that peripheral venous disease may sometimes be post-thrombotic syndrome as a result of a previous unrecognized DVT.

Common femoral vein dimensions and hemodynamics including Valsalva response as a function of sex, age, and ethnicity in a population study.

PURPOSE: In this study we assessed the normal common femoral vein (CFV) dimensions and related hemodynamics in a cohort assembled to permit contrasts by means of sex, age, and ethnicity. METHODS: The CFV diameter and the flow velocity were analyzed by means of duplex ultrasonography at rest and with a standardized Valsalva maneuver, with the subject in a 15% reverse Trendelenberg position. Mean levels of each of the CFV measurements were analyzed with age category, sex, and ethnicity, each adjusted for the other two. Multiple linear regression was used as a means of assessing the independent associations of age, sex, ethnicity, body mass index (BMI), and height to the CFV measurements. RESULTS: The average CFV diameter at rest was 11.84 mm, increasing to 14.27 mm during the Valsalva maneuver. There was a significant (P <.0001) decline in both diameter measures beginning in patients 60 years old. The CFV diameter was larger in men (12.90 mm) than in women (11.22 mm; P <.0001). The average CFV diameter in Hispanics, Africian Americans, and Asians was significantly smaller (P <.001) than in the non-Hispanic whites in multivarate analysis. The independence of these associations was confirmed by means of multivariate analysis, and positive associations of CFV diameter with height and BMI were documented. The Valsalva response was higher in men than in women (2.67 mm vs 2.29 mm), but the percentage change was similar. CFV velocity at rest decreased significantly (P <.0001) in patients older than 50 years. The mean CFV velocity was 13.87 cm/s, and the values were significantly (P <.0001) higher in women (14.58 cm/s) than in men (12.67 cm/s). In multivariate analysis CFV velocity was higher in African Americans than in the other ethnic groups. We also documented an independent inverse association of CFV with BMI. The CFV velocity response (peak expiration post-Valsalva) increased significantly at all ages, from 52% to 83%. The percentage increase in women (68%) was slightly higher than that in men (58%). African American subjects had a somewhat higher percentage increase (74%) than the other three ethnic groups (63% to 64%). Because the flow rate is determined more by the diameter than the velocity, CFV flow associations were similar to those for diameter. Because an older age predicted both decreased diameter and velocity, the flow reduction with age was pronounced. CONCLUSION: Quantitative normative data that are age-, sex-, and ethnic group-specific are reported on CFV diameter, velocity, and total flow rate, both at rest and with the Valsalva maneuver. CFV diameter, velocity, and flow rate varied significantly as a function of age, sex, ethnicity, height, and BMI. The data also provide a baseline assessment for subsequent evaluations of changes with time in this cohort.

The correlation between the severity of peripheral arterial disease and carotid occlusive disease.

Peripheral arterial disease (PAD) and carotid occlusive disease (COD) are both known to be specific manifestations of atherosclerosis. Because they both have a common cause, it is reasonable to hypothesize that they should correlate with each other to a certain extent, and previous studies have shown that there is a correlation between the prevalence of PAD and COD. The purpose of this study was to determine whether a correlation exists between the severity of PAD and the severity of COD by retrospectively looking at a group of 203 patients who underwent non-invasive testing for suspicion of PAD at the San Diego VA Hospital or UCSD Medical Center, and who also had a non-invasive duplex carotid scan. The severity of PAD was assessed by segmental blood pressure ratios (leg segment/arm ratio) in each leg taken at the toe, ankle, and below the knee, as well as the peak flow velocity of the posterior tibial artery. The severity of COD was assessed by duplex ultrasound scans of six distinct segments of the carotid artery system: the right and left common, internal, and external carotid arteries. Correlation analysis showed r=0.23 (p=0.001) when comparing a PAD aggregate standard score with the number of diseased carotid arteries (>50% stenosis), and r=0.23 (p=0.001) when comparing a PAD aggregate standard score with an average COD score. Because about 50% of the patients had undergone surgical intervention on their leg or carotid arteries, another correlation analysis restricted to patients with no surgical interventions (n = 97) was performed. The above correlations were slightly attenuated in this analysis, r=0.21 (p=0.043) and r=0.17 (p= 0.092), respectively. The results indicate that there is a modest but significant correlation between the severity of PAD and the severity of COD in a population with a high prevalence of both.

Quantitative and qualitative progression of peripheral arterial disease by non-invasive testing.

There is little information on the progression of peripheral arterial disease (PAD) over time. A series of 508 patients with a prior examination for PAD were contacted and brought in for follow-up to evaluate the natural history of PAD. A total of 85 patients were excluded because they had interventions in both limbs prior to their return visit. Progression was assessed in the remaining 423 patients for a total of 755 limbs, both quantitatively and qualitatively using six categories of PAD severity. There was a modest overall categorical progression of disease: 228 limbs (30.2%) displayed categorical progression, while 172 limbs (22.8%) improved over a 4.6-year average follow-up. Through analysis of quantitative change, it was determined that more quantitative progression occurred than was evident from categorical progression. Two of the three non-invasive tests employed, the ankle/brachial index (ABI) and posterior tibial peak forward flow velocity (peak PT), showed statistically significant progression during follow-up: mean ABI change = -0.019, 95% confidence interval (CI)= -0.031 to -0.007; mean peak PT change = -2.32 cm/s, 95% CI = -3.20 to -1.44. The toe/brachial index (TBI) also suggested progression: mean change= -0.013, but the 95% CI included no change. Standard scores (sum of the Z-scores for ABI, peak PT and TBI) were calculated. The standard score progressed approximately 0.34 units (standard deviations), p-value <0.001, over 4.6 years; or about 0.07 standard deviations per year. There were independent and statistically significant (p<0.05) associations between the rate of PAD progression (standard score change) and age, diabetes, classic ('Rose') intermittent claudication, moderate to severe PAD in the same limb, moderate to severe PAD in the contralateral limb and future therapeutic intervention. There were independent and suggestive associations (0.05

The generalized nature of atherosclerosis: how peripheral arterial disease may predict adverse events from coronary artery disease.

Non-invasive measurements, especially segmental pressure ratios and flow measurements, are useful for gauging the severity of peripheral arterial disease (PAD). Although the incidence of PAD is similar for men and women, men are more likely to have severe disease, while women usually have more moderate or asymptomatic disease. Published reports confirm the clinical impression that patients with PAD are more likely to have both coronary artery disease and cerebrovascular disease than those without PAD. However, the degree of overlap is a function of the sensitivity of the diagnostic assessments for the three conditions. A San Diego population study found that the incidence of PAD may be underestimated, with many patients being asymptomatic. Based on blood flow measurements, the study found that 11.9% of the study population had large vessel PAD. Morbidity from both coronary heart disease and stroke was increased in people with PAD, who were 2.5 times more likely to present with morbidity from cardiovascular disease (CVD) than those who did not have PAD. Several studies have now confirmed the strong predictive value of PAD for subsequent CVD mortality and that the risk of CVD mortality increases with the severity of PAD.

The epidemiology of peripheral arterial disease: importance of identifying the population at risk.

Data from the Framingham Study and other population studies indicate that intermittent claudication (IC) sharply increases in late middle age and is somewhat higher among men than women. Noninvasive testing in populations indicates that the true prevalence of peripheral arterial disease (PAD) is at least five times higher than would be expected based on the reported prevalence of IC. Peripheral arterial disease correlates most strongly with cigarette smoking and either diabetes or impaired glucose tolerance. Other risk factors for PAD include hypertension; low levels of high-density lipoprotein cholesterol; and high levels of triglycerides, apolipoprotein B, lipoprotein(a), homocysteine, fibrinogen and blood viscosity. Individuals with PAD are more likely to have coronary heart disease and cerebrovascular disease than those without PAD. Because of the high risk of both nonfatal and fatal cardiovascular disease (CVD) events in PAD patients, individuals with evidence of PAD should undergo both a careful examination of the entire cardiovascular system and aggressive modification of CVD risk factors.

The correlation between symptoms and non-invasive test results in patients referred for peripheral arterial disease testing.

The WHO/Rose questionnaire has served as the epidemiologic and clinical standard in the assessment of leg pain in patients with peripheral arterial disease (PAD) for over three decades. However, the structure of this questionnaire does not allow assessment of leg-specific (i.e. right versus left) symptoms. We studied 508 patients aged 39-95 years (mean 68 years), initially referred for PAD non-invasive testing. A revised questionnaire, the San Diego Claudication Questionnaire, was administered which allowed determination of leg-specific symptoms and evaluated thigh and buttock as well as calf pain. Leg-specific symptoms were categorized into no pain, pain at rest, non-calf claudication, non-Rose calf claudication, and Rose claudication. At the same visit, the ankle brachial index, the toe brachial index, and peak posterior tibial flow velocity were measured by Doppler ultrasound and five categories of non-invasive results by type and severity of PAD were defined. Legs with previous intervention (Rx), surgery or angioplasty, were evaluated separately. Claudication was reported in 42% of no Rx legs and 50% of Rx legs; 40% of claudication was atypical (not Rose); 64% of no Rx and 81% of Rx legs had PAD by non-invasive testing, and 27% of affected legs had severe PAD. The correlation between the severity of symptoms and the severity of ipsilateral PAD in no Rx legs was r = -0.40, p < 0.001. In Rx legs, this correlation was somewhat less (r = 0.27, p < 0.001) due to more symptomatology at lesser degrees of PAD, suggesting reporting bias and/or more residual disease than evident from non-invasive testing. To our knowledge, these results provide the first comparison between a standardized assessment of leg pain and the severity of ipsilateral PAD by non-invasive testing.

Corpus callosum: region-specific effects of sex, early experience and age.

In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization.