Measures Of Subclinical Disease Research Articles

The association of coronary artery calcification and carotid artery intima-media thickness with distinct, traditional coronary artery disease risk factors in asymptomatic adults.

Coronary artery calcification (CAC) and common carotid artery intima-media thickness (CIMT) are measures of subclinical vascular disease. This 2000-2006 study aimed to characterize the associations among coronary artery disease risk factors, CAC quantity, and CIMT and to estimate shared genetic and environmental contributions to both CAC and CIMT among 478 asymptomatic Amish adults in Lancaster County, Pennsylvania. Heritability for CAC quantity and CIMT, adjusted for age and sex, was 0.42 (P = 0.0001) and 0.29 (P = 0.003), respectively. CAC quantity and CIMT were modestly correlated (adjusted r = 0.14, P = 0.003) but showed little evidence of shared genetic or environmental factors. However, significant genetic correlations were found for CAC quantity and total cholesterol (0.44 (standard error, 0.19); P = 0.03), for CAC quantity and low density lipoprotein cholesterol (0.55 (standard error, 0.17); P = 0.005), and for CIMT and waist circumference (0.58 (standard error, 0.25); P = 0.046), suggesting shared genes for these risk factors and measures of subclinical disease. Results suggest that some of the same genes influence variation in CAC and low density lipoprotein cholesterol, whereas a different set of genes influences variation in CIMT and waist circumference.

Clinical and subclinical cardiovascular disease and kidney function decline in the elderly

Objective Kidney function decline in elderly persons may be the result of microvascular atherosclerosis. As a proxy for the renovascular system, we evaluated the association of clinical and subclinical cardiovascular disease (CVD) with kidney function decline. Methods This study included 4380 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged ≥65 from 4 U.S. communities. Creatinine and cystatin C were measured at baseline, year 3, and year 7; eligible subjects had at least two measures. Creatinine-based estimated glomerular filtration rate (eGFR creat) was calculated using the MDRD equation. Rapid kidney function decline was defined as an annual eGFR loss >3 mL/min/1.73 m 2. Predictors of rapid kidney decline included prevalent and subclinical measures of CVD. Results Mean decline in eGFR creat was 0.4 ± 2.6/year; 714 (16%) had rapid progression. In multivariate models adjusted for demographics, cardiovascular risk factors, and inflammation, prevalent stroke (OR, 95% CI: 1.55, 1.16–2.08) and heart failure (OR, 95% CI: 1.80, 1.40–2.31) were independent predictors of rapid kidney decline. Among persons without clinical CV, the subclinical disease measures ankle–arm index <0.9 (OR, 95% CI: 1.67, 1.25–2.24), common carotid intima–media thickness (≥1.14 mm) (OR, 95% CI: 1.52, 1.12–2.06) and internal carotid intima–media thickness (>1.82 mm) (OR, 95% CI: 1.50, 1.12–2.02) had independent associations with rapid kidney function decline. Results were similar using cystatin C. Conclusion Clinical atherosclerosis and heart failure and subclinical measures of CVD have independent associations with kidney function decline progression in the elderly, suggesting an underlying role of renal atherosclerosis.

Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

The cholesteryl ester transfer protein (CETP) plays a key role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP activity and concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration; however, controversies remain about whether these genetic variants are associated with atherosclerosis. We genotyped the CETP R451Q, A373P, −629C/A, Taq1B, and −2505C/A polymorphisms in a cohort of Caucasian, Chinese, African-American, and Hispanic individuals within the Multi-Ethnic Study of Atherosclerosis. Genotypes were examined in relationship to HDL-C, CETP activity, CETP concentration, and three measures of subclinical cardiovascular disease (CVD): coronary artery calcium (CAC) measured by fast CT scanning, carotid intimal-medial thickness (IMT), and carotid artery plaque measured by ultrasonography. Carriers of the 451Q and 373P alleles have a significantly higher CETP concentration (22.4% and 19.5%, respectively; p < 0.001) and activity (13.1% and 9.4%, respectively; p < 0.01) and lower HDL-C (5.6% and 6.0%, respectively; p < 0.05). The minor alleles of the R451Q and A373P polymorphisms are associated with the presence of CAC, even after adjusting for CVD risk factors and HDL-C ( p = 0.006 and p = 0.01, respectively). The R451Q polymorphism is also associated with presence of carotid artery plaque ( p = 0.036). Polymorphism is associated with neither common nor internal carotid IMT. We confirmed that the −629A, Taq1B B2, and −2505A alleles are significantly associated with lower CETP concentration (20.8%, 25.0%, and 23.7%, respectively; p < 0.001) and activity (14.8%, 19.8%, and 18.4%, respectively; p < 0.001) and higher HDL-C concentration (9.7%, 11.5%, and 10.4%, respectively; p < 0.01). However, we did not find any associations between these non-coding polymorphisms and subclinical CVD.

Cardiovascular Risk Factors and Incident Acute Renal Failure in Older Adults

Although the elderly are at increased risk for acute renal failure, few prospective studies have identified risk factors for acute renal failure in the elderly. The associations of cardiovascular disease risk factors, subclinical cardiovascular disease, and clinical coronary heart disease with the risk for development of acute renal failure were examined in older adults in the Cardiovascular Health Study, a prospective cohort study of community-dwelling older adults. Incident hospitalized cases of acute renal failure were identified through hospital discharge International Classification of Diseases, Ninth Revision codes and confirmed through physician diagnoses of acute renal failure in discharge summaries. Acute renal failure developed in 225 (3.9%) of the 5731 patients during a median follow-up period of 10.2 yr. In multivariate analyses, diabetes, current smoking, hypertension, C-reactive protein, and fibrinogen were associated with acute renal failure. Prevalent coronary heart disease was associated with incident acute renal failure, and among patients without prevalent coronary heart disease, subclinical vascular disease measures were also associated with acute renal failure: Low ankle-arm index (< or =0.9), common carotid intima-media thickness, and internal carotid intima-media thickness. In this large, population-based, prospective cohort study, cardiovascular risk factors and both subclinical and clinical vascular disease were associated with incident acute renal failure in the elderly.

Alteration of myocardial characteristics and function in patients with obstructive sleep apnea

The aim of the present study was to examine subclinical effect of the severity of obstructive sleep apnea (OSA) on myocardial structural changes and function using echocardiographic integrated backscatter and tissue Doppler imaging. Fifty patients with suspected OSA underwent overnight polysomnography and echocardiographic assessment. The myocardial reflectivity and mitral annular velocity were obtained as measures of subclinical myocardial disease. The OSA patients had lower annular velocity and higher myocardial reflectivity compared with non-OSA subjects, although global systolic function was similar. In conclusion, OSA can affect myocardial integrity as well as myocardial diastolic function.

Long-term Exposure to Ambient Particulate Matter and Prevalence of Subclinical Atherosclerosis in the Multi-Ethnic Study of Atherosclerosis

Exposure to airborne particulate matter has been linked to cardiovascular events. Whether this finding reflects an effect of particulate matter exposure on the triggering of events or development of atherosclerosis remains unknown. Using data from the Multi-Ethnic Study of Atherosclerosis collected at baseline (2000-2002), the authors investigated associations of 20-year exposures to particulate matter with measures of subclinical disease (coronary calcium, common carotid intimal-medial thickness, and ankle-brachial index) in 5,172 US adults without clinical cardiovascular disease. Particulate matter exposures for the 20 years prior to assessment of subclinical disease were obtained from a space-time model of Environmental Protection Agency monitor data linked to residential history data for each participant. Intimal-medial thickness was weakly, positively associated with exposures to particulate matter <10 microm in aerodynamic diameter and <2.5 microm in aerodynamic diameter after controlling for age, sex, race/ethnicity, socioeconomic factors, diet, smoking, physical activity, blood lipids, diabetes, hypertension, and body mass index (1-4% increase per 21-microg/m(3) increase in particulate matter <10 microm in aerodynamic diameter or a 12.5-microg/m(3) increase in particulate matter <2.5 microm in aerodynamic diameter). No consistent associations with other measures of atherosclerosis were observed. There was no evidence of effect modification by sociodemographic factors, lipid status, smoking, diabetes, body mass index, or site. Results are compatible with some effect of particulate matter exposures on development of carotid atherosclerosis.

Whole grain intake and its cross-sectional association with obesity, insulin resistance, inflammation, diabetes and subclinical CVD: The MESA Study

We examined the relationship between whole grain intake and obesity, insulin resistance, inflammation, diabetes and subclinical CVD using baseline data from the Multi-Ethnic Study of Atherosclerosis. Whole grain intake was measured by a 127-item FFQ in 5496 men and women free of CHD and previously known diabetes. Mean whole grain intake was 0.5 (sd 0.5) servings per d; biochemical measures reflect fasting levels. After adjustment for demographic and health behaviour variables, mean differences for the highest quintile of whole grain intake minus the lowest quintile of intake were 0.6 kg/m2 for BMI, 0.36 mg/l for C-reactive protein, 0.82 micromol/l for homocysteine, 0.15 mU/l*mmol/l for homeostasis model assessment (HOMA), 0.48 mU/l for serum insulin, 2.0 mg/dl for glucose and 5.7 % for prevalence of newly diagnosed impaired fasting glucose (glucose >or= 100 mg/dl or diabetes medication). These differences represent 11-13 % of a standard deviation of BMI, HOMA, glucose and impaired fasting glucose, but 23 %, 52 % and 80 % of a standard deviation of homocysteine, C-reactive protein and insulin, respectively. An inverse association between whole grains and urine albumin excretion was suggested but retained statistical significance after adjustment only in Chinese and Hispanic participants. No associations were observed between whole grain intake and two subclinical disease measures: carotid intima-media thickness and coronary artery calcification. Concordant with previous research, whole grain intake was inversely associated with obesity, insulin resistance, inflammation and elevated fasting glucose or newly diagnosed diabetes. Counter to hypothesis, however, whole grain intake was unrelated to subclinical CVD.

Associations Among Walking Performance, Physical Activity, and Subclinical Cardiovascular Disease

An objective measure of walking performance could have several potential applications in clinical settings. The cross-sectional relationships among long distance corridor walk (LDCW) time, physical activity, and subclinical cardiovascular disease (CVD) measures were examined before group randomization in 492 participants (mean age, 57.0+/-2.9 years) from the Women On the Move Through Activity and Nutrition (WOMAN) study, a randomized clinical trial involving postmenopausal women. Longer walk times were significantly associated with higher body mass index (P<0001), average waist circumference (P<0001), and lower levels of physical activity (P<002). The proportion of detectable coronary artery calcification and median aortic pulse wave velocity levels were significantly higher among those with slower walk times (P<002 and P<.001, respectively). Findings from the current report support the utility of the LDCW to identify women at higher risk for CVD who may be candidates for further cardiovascular testing or intensive lifestyle intervention.

Can we learn more about the etiology of cardiovascular disease?

Atherosclerosis is a foreign body that is associated with an inflammatory response. The inflammatory response is clearly important both in terms of the progression of the atherosclerosis and subsequent changes in the plaque morphology that leads to thrombogenesis and clinical disease. However, the ability to identify these markers in the serum when their effects are primarily local may be very limited. We probably do not need another plethora of adhe sion molecules, cytokines and growth factors, each with a modest relative risk and then further debate about which of the numerous variables is more important. Unfortunately, the absence of measures of subclinical disease in most of these populations pre cludes the ability of separating the effects on ath erosclerosis and vessel wall from thrombogenesis and fibrinolysis. Obesity and total body fat, visceral fat and muscle fat, are important determinants of the levels of adipokines, hormone metabolism, liver enzymes, proteins and insulin resistance, which has now been labeled the "metabolic syndrome" [5]. There is, however, little evidence that these adipokines or other markers of body fat distribution play an independent role in atherosclerosis and CVD beyond the collin earity with lipoprotein metabolism, salt retention, elevated blood pressure (BP), insulin resistance and

The relationship between physical activity and lipoprotein subclasses in postmenopausal women

This study's objective was to determine if the association between physical activity and lipids and lipoprotein subclasses in postmenopausal women varies by hormone therapy (HT) use. The cross-sectional relationship between physical activity and lipid and lipoprotein subclass relationship was examined before group randomization in 485 postmenopausal (mean age 56.9 [2.9] y) white and African American women from the Woman On the Move through Activity and Nutrition study. This study is a randomized clinical trial designed to test whether a lifestyle intervention will reduce subclinical cardiovascular disease measures. Hormone therapy users (n = 286) were significantly (P < 0.05) younger, less likely to be African American, reported higher levels of physical activity, large very low-density lipoprotein particles (VLDL-P), and medium high-density lipoprotein particles (HDL-P), had a larger mean HDL-P size, and lower levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, small HDL-P, and small VLDL-P than nonusers (n = 196). Physical activity was significantly associated with favorable lipoprotein and lipid levels, regardless of HT use. Some relationships were found to vary significantly by HT use. In nonusers, mean HDL-P and LDL particles (LDL-P) size was significantly larger (P = 0.01 and 0.05, respectively) and total and small LDL-P were significantly lower (both P = 0.02) as activity increased. These relationship were not found in HT users. Physical activity was significantly related to some lipoprotein subclasses regardless of HT; however, several key lipoprotein subclasses were associated with higher levels of activity only among non-HT users.

Association Between Levels of Blood Pressure and Measures of Subclinical Disease: Multi-Ethnic Study of Atherosclerosis

High blood pressure (BP) is associated with the presence and severity of subclinical disease. Less is known about associations between normal levels of BP and various measures of subclinical disease. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled 6814 participants free of clinical cardiovascular disease (38% white, 28% African American, 22% Hispanic, and 12% Asian). The baseline examination included standardized measures of BP, common carotid intimal-medial thickness determined by ultrasonography, coronary artery calcium by computed tomography, and left ventricular mass by magnetic resonance imaging. Participants with treated hypertension (n = 2173) were excluded. Statistical methods included analysis of variance, linear regression, and chi(2) tests. Among the 4640 participants, BP was strongly related to age and African American ethnicity. Carotid intimal-medial thickness was directly associated with systolic BP (SBP) and inversely associated with diastolic BP (DBP, P < .001 for both). For SBP in men, for instance, the adjusted regression coefficient was 0.058 mm per 1 SD (21 mm Hg; 95% CI, 0.045 to 0.070), and for SBP in women it was 0.043 (95% CI, 0.033 to 0.052). Left ventricular mass was directly related to SBP and DBP. The proportion with non-zero calcium scores increased with SBP but decreased with DBP. The range of BP examined in this study fell largely within the normal or prehypertension stage. In cross-sectional analysis of data from a population-based study, these untreated levels of BP were associated with a variety of measures of subclinical cardiovascular disease.

Characteristics and Baseline Clinical Predictors of Future Fatal Versus Nonfatal Coronary Heart Disease Events in Older Adults

Although >80% of annual coronary heart disease (CHD) deaths occur in adults aged >65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described. The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or =65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30% were fatal. Case fatality decreased slightly over time, ranging from 28% to 30% per year in the early 1990s versus 23% by 2000-2001; with adjustment for age at MI and gender, there was a 6% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups. Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD.

Plasma Sphingomyelin and Subclinical Atherosclerosis: Findings from the Multi-Ethnic Study of Atherosclerosis

Plasma sphingomyelin has been shown to be an independent risk factor for coronary heart disease, but the relation of plasma sphingomyelin to earlier, subclinical atherosclerotic disease has not been reported. The authors examined the association between plasma sphingomyelin and three measures of subclinical cardiovascular disease (carotid intimal-medial wall thickness, ankle-arm blood pressure index, and Agatston coronary artery calcium score) among 6,814 middle-aged, asymptomatic adults in the Multi-Ethnic Study of Atherosclerosis, which was initiated in 2000. The sphingomyelin level was positively correlated with lipids and the Framingham risk score (p < 0.01 for both), and the mean level was higher in women than men (50 (standard deviation (SD), 16) vs. 45 (SD, 15) mg/dl) (p < 0.01) and higher in never versus current smokers (49 (SD, 16) vs. 45 (SD, 17) mg/dl) (p < 0.01). Women with sphingomyelin levels of 60 or more mg/dl had more severe subclinical disease by all three measures than did the referent group with sphingomyelin levels of 39 or less mg/dl, although associations were not significant after multivariate adjustment for standard cardiovascular disease risk factors. Men with sphingomyelin levels of 60 or more mg/dl versus those with sphingomyelin levels of 39 or less mg/dl had higher calcium scores (135 vs. 99 Agatston units) (p = 0.01). These observations are consistent with the hypothesis that plasma sphingomyelin is in the biologic pathway that mediates the risk for subclinical disease attributable to standard cardiovascular disease risk factors.

Usefulness of Aortic Root Dimension in Persons ≥65 Years of Age in Predicting Heart Failure, Stroke, Cardiovascular Mortality, All-Cause Mortality and Acute Myocardial Infarction (from the Cardiovascular Health Study)

Echocardiographic measures of left ventricular (LV) function and structure as well as left atrial size have been reported to predict adverse cardiovascular disease (CVD) outcomes. Although anatomic changes of the aortic root are likely to reflect effects of hypertension and atherosclerosis, few data are available on the predictive value of aortic root dimension (ARD) for outcome in free-living populations. The purpose of this investigation was to determine whether in a cohort of patients aged > or = 65 years ARD was associated with traditional coronary heart disease (CHD) risk factors and with 10-year incident CVD outcomes. In the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Health Study, 3,933 free-living black and white men and women > or = 65 years of age without prevalent CVD had 2-dimensional directed M-mode echocardiographic measurements of ARD as part of a comprehensive evaluation. ARD was associated with age and gender (greater in men) but not race. ARD was also positively associated with diastolic blood pressure, LV hypertrophy, major electrocardiographic abnormalities, and other echocardiographic measures, including LV mass, ventricular septal and posterior wall thickness, and LV dimension. After adjustment for other known risk factors, high ARD was associated with an increased risk for incident congestive heart failure (CHF) in men (hazard ratio for upper compared with all other quintiles 1.47, p = 0.014), stroke in men and women (hazard ratio 1.39 per cm, p = 0.015), CVD mortality in men and women (hazard ratio 1.48 per cm, p = 0.007), and total mortality in men and women taking antihypertensive medications (hazard ratio 1.46 per cm, p = 0.007), but not with incident myocardial infarction (MI) (hazard ratio 0.89, p = 0.39). In conclusion, in a cohort of patients aged > or = 65 years without clinical CVD at baseline, ARD was associated with several CHD risk factors and measures of subclinical disease and was predictive of incident CHF, stroke, CVD mortality, and all-cause mortality, but not of incident MI.

The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study

African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery intima-medial thickness (IMT) were present in members of The Diabetes Heart Study families. In a bi-racial cohort of 1,180 individuals from families enriched for members with type 2 diabetes, we calculated coronary and carotid artery calcified plaque using fast-gated helical computed tomography, and measured carotid artery IMT and clinical risk factor profiles. Generalised estimating equations were used to test for an association between measures of subclinical cardiovascular disease and ethnicity and sex. After adjustment for age, ethnicity and kidney function, African-Americans had significantly lower amounts of coronary artery calcified plaque (mean+/-SE) (866+/-158 vs 1,915+/-135, respectively; p=0.0466) and carotid artery calcified plaque (179+/-51 vs 355+/-27, respectively; p=0.0240) relative to whites, despite having increased carotid IMT (0.71+/-0.01 vs 0.67+/-0.004 cm, respectively; p=0.0007), and higher blood pressure, albuminuria and HbA1c. Sex-specific analyses revealed that African-American men had significantly lower coronary and carotid artery calcified atheroma than white men. In women, ethnic differences in calcified carotid artery plaque, but not coronary artery plaque, were observed. In families enriched for members with type 2 diabetes, African-American men had markedly lower levels of coronary and carotid artery calcified plaque than white men, despite increased carotid artery IMT and conventional risk factors. These findings suggest that susceptibility to subclinical cardiovascular disease differs markedly according to ethnicity and sex.

Psychosocial Stress and Cardiovascular Risk: What is the Role of Daily Experience?

We describe an ecological momentary assessment (EMA) protocol designed to measure daily life experiences along several psychosocial dimensions (Social Conflict, Task Demand, Decisional Control, Negative Affect, and Arousal) hypothesized to be relevant for cardiovascular disease risk. In a large community sample, these assessments have been administered in conjunction with ambulatory blood pressure (ABP) monitoring and measures of subclinical cardiovascular disease. Several results have emerged that support the promise of this approach. First of all, each of these dimensions of experience appears to be a trigger for cardiovascular activation, with movement on each scale being associated with significant within-person changes in heart rate and blood pressure in the natural environment. Second, there appear to be individual differences in physiological responsiveness to these dimensions of daily experience, with such differences being associated in some cases with laboratory-based assessments of cardiovascular reactivity, as might be expected. Third, EMA ratings are associated in several instances with (between-person) stable individual differences in ABP readings. And finally, we have found that some of the characteristics defined by our EMA ratings are related to measures of subclinical atherosclerosis. Such effects appear to be mediated, in part, by ABP. The advantages of using EMA measures for capturing the effects of psychosocial stressors are highlighted by comparing the predictive validity of these daily life assessments to traditional global self-reports. We conclude by describing future plans for use of this type of assessment protocol for helping us to characterize psychosocial characteristics relevant to cardiovascular disease risk. Personality and social processes during daily living may have an important impact not only on psychological functioning but also on physical health and disease. In this article we review our recent work involving the assessment of daily experience as a means of better understanding the role of psychosocial stress in cardiovascular disease risk. First, we outline the rationale for our interest in daily experience sampling for examining these processes, and we describe the methods we have adopted for this purpose. Next, we review findings from a recent study in which we have used these approaches to examine the role of psychosocial stress on ABP and atherosclerosis in a community-dwelling sample. We compare our approach to more traditional (global self-report and laboratory-observation) methods for examining these relationships in humans, and we discuss potential future directions for use of daily experience sampling in studies of health and behavior.

A genetic and epidemiologic study of cardiovascular disease in Alaska natives (GOCADAN): design and methods

This article is a report of the design and methods of the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study. This longitudinal, population-based study was initiated to investigate the genetic determinants of cardiovascular disease and its risk factors. Between October 2000 and April 2004, this family study enrolled 1,214 Eskimos from several coastal villages in the Norton Sound region of Western Alaska. Examinations included a physical, laboratory determinations, and measures of subclinical disease. This study will generate a genome-wide scan for loci influencing cardiovascular disease-related traits. Relations between subclinical atherosclerosis and markers of inflammation will be examined using historic and newly drawn samples. The study will provide data on CVD prevalence, risk factors and the relative contribution of genetic and environmental determinants in Alaska Native peoples. Data from this study will contribute to the delivery of health-care and prevention of CVD in Alaska Eskimos and other populations. (Int J Circumpolar Health 2005; 64(3):206–221)

Renal artery calcified plaque associations with subclinical renal and cardiovascular disease

The prognostic significance of renal artery calcified plaque (RAC) and its relationship with renal function, albuminuria, and systemic atherosclerosis are unknown. Calcified atherosclerotic plaque was measured in the renal arteries of 96 unrelated Caucasian subjects with type 2 diabetes mellitus (DM) using four-channel multidetector-row computed tomography (MDCT4). Renal artery calcium was measured as the sum of ostial and main renal artery calcium scores. Participants also underwent MDCT scanning to measure coronary artery calcium (CAC), carotid artery calcium, common iliac artery calcium, infra-renal aorta calcium, and B-mode ultrasound to measure carotid artery intima-medial thickness (IMT). Spearman's rank correlation coefficients were used to assess associations between RAC and measures of subclinical renal and cardiovascular disease. Partial correlation coefficients were computed to adjust for the potential confounding effects of age, gender, body mass index (BMI), DM duration, smoking, and serum cholesterol and triglyceride levels. Characteristics of the study group were 54% (52/96) female with a mean +/- SD (median) age 62.8 +/- 8.4 (62.5) years, DM duration 10.6 +/- 6.3 (8.0) years, hemoglobin A1C 7.5 +/- 1.5 (7.2)%, BMI 32.1 +/- 6.3 (31.1) kg/m(2), serum creatinine concentration 1.11 +/- 0.18 (1.10) mg/dL, urine albumin:creatinine ratio (ACR) 105.3 +/- 423.1 (17.6) mg/g, modified MDRD equation glomerular filtration rate (GFR) 64.3 +/- 12.6 (63.6) mL/min, RAC 372 +/- 799 (101), CAC 1819 +/- 2594 (622), carotid artery calcium 264 +/- 451 (72), and B-mode ultrasound carotid IMT 0.70 +/- 0.12 (0.69) mm. Sixty-five percent of subjects (62/96) had detectable RAC. Renal artery calcium was significantly associated with CAC (r= 0.50, P < 0.0001), carotid artery calcium (r= 0.58, P < 0.0001), common iliac artery calcium (r= 0.45, P < 0.0001), infra-renal aorta calcium (r= 0.70, P < 0.0001), IMT (r= 0.40, P= 0.0004), diastolic blood pressure (r=-0.33, P= 0.0009), BMI (r=-0.19, P= 0.0573), and age (r= 0.54, P < 0.0001). There was no association between RAC and GFR (r=-0.15, P= 0.1637) or between RAC and urine ACR (r= 0.07, P= 0.5083). Renal artery calcium is strongly associated with older age, diastolic blood pressure, BMI, carotid artery IMT, and coronary, carotid, common iliac artery, and infra-renal aorta calcium in Caucasians with type 2 diabetes mellitus. Renal artery calcium, similar to CAC and IMT, appears to be a useful noninvasive marker of subclinical atherosclerosis. However, RAC is not significantly associated with either GFR or albuminuria.

Relationship of adiposity to subclinical atherosclerosis in obese patients with type 2 diabetes.

There is an increased prevalence of macrovascular disease in type 2 diabetes. The pathogenesis has been related to metabolic risk factors, insulin resistance, and obesity. One of the strongest predictors is the presence of subclinical atherosclerosis. This study was designed to examine the relationship between obesity and regional patterns of adiposity, insulin resistance, and five independent measures of subclinical atherosclerosis. Fifty-two overweight and obese men and women with type 2 diabetes of relatively short known duration were examined. Measures of subclinical vascular disease were assessment of arterial stiffness by pulse wave velocity, ultrasound measurement of the carotid artery intimal-medial thickness and plaque index, and measurement of the extent of coronary and aortic calcification using electron beam computed tomography. Insulin resistance was measured using the hyperinsulinemic euglycemic clamp. Body composition was measured using DXA and computed tomography. Adiposity was a strong determinant of pulse wave velocity. Carotid intimal-medial thickness was correlated with age, low-density lipoprotein-cholesterol, and hyperglycemia, but not with adiposity. Hyperglycemia and plasma activator inhibitor-1 were significant correlates of the carotid artery plaque index. Coronary calcium scores were significantly correlated with age and interleukin-6 and significantly and negatively correlated to insulin sensitivity index. These findings suggest that obesity may play an important role in the early phase of subclinical macrovascular disease related to vessel stiffness, whereas hyperglycemia and insulin resistance in conjunction with other risk factors have important roles in progression from vessel stiffness to atheroma formation in type 2 diabetes.

Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals

ObjectivesThis study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events. BackgroundEnd-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear. MethodsWe analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level ≥1.5 mg/dl in men or ≥1.3 mg/dl in women. ResultsAn elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine. ConclusionsElevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.