Depressive Symptoms Are Associated with Reduced Cardiac Function Among Hispanics: Results from the PREVENCION Study.

BACKGROUND: Depressive symptoms are common among patients with heart failure and are often associated with adverse outcomes, including re-hospitalization and mortality. However, little is known about the association between depressive symptoms and subclinical markers of heart failure and cardiac function in community-based samples and little research has focused on South American Hispanics. The current study examined the cross-sectional association between depressive symptoms and cardiac function in South American Hispanic community-based adults. METHODS: Participants included 527 adults enrolled in the Peruvian Study of Cardiovascular Disease (PREVENCION). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS). Markers of cardiac function were assessed by impedance cardiography and included cardiac output, cardiac index, stroke volume, and stroke volume index. Several multiple regression analyses were used to examine the association between depressive symptoms and markers of cardiac function. RESULTS: In adjusted analyses, depressive symptoms were associated with reduced cardiac output, cardiac index, stroke volume, and stroke volume index. These associations remained significant between depressive symptoms and cardiac output (ß = - 0.106, p = 0.014), cardiac index (ß = - 0.099, p = 0.029), and stroke volume (ß = - 0.095, p = 0.022), and a trend was still observed between depressive symptoms and stroke index (ß = - 0.083, p = 0.061), even after having controlled for demographic factors (age, gender, education), cardiovascular risk factors (smoking status, body mass index, low- and high-density lipoprotein cholesterol, triglycerides, fasting glucose, serum creatinine), and comorbidities (diabetes mellitus, hypertension, hypercholesterolemia). CONCLUSIONS: In the PREVENCION sample tested, depressive symptoms were independently associated with cardiac function among Hispanic adults, even above and beyond pertinent factors such as demographic factors, cardiovascular risk factors, and comorbidities. Future studies should determine whether depressive symptoms are prospectively associated with systolic dysfunction, and examine the bio-behavioral pathways of this association.

Risk score for first-screening of prevalent undiagnosed chronic kidney disease in Peru: the CRONICAS-CKD risk score.

BACKGROUND: Chronic Kidney Disease (CKD) represents a great burden for the patient and the health system, particularly if diagnosed at late stages. Consequently, tools to identify patients at high risk of having CKD are needed, particularly in limited-resources settings where laboratory facilities are scarce. This study aimed to develop a risk score for prevalent undiagnosed CKD using data from four settings in Peru: a complete risk score including all associated risk factors and another excluding laboratory-based variables. METHODS: Cross-sectional study. We used two population-based studies: one for developing and internal validation (CRONICAS), and another (PREVENCION) for external validation. Risk factors included clinical- and laboratory-based variables, among others: sex, age, hypertension and obesity; and lipid profile, anemia and glucose metabolism. The outcome was undiagnosed CKD: eGFR < 60 ml/min/1.73m2. We tested the performance of the risk scores using the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios. RESULTS: Participants in both studies averaged 57.7 years old, and over 50% were females. Age, hypertension and anemia were strongly associated with undiagnosed CKD. In the external validation, at a cut-off point of 2, the complete and laboratory-free risk scores performed similarly well with a ROC area of 76.2% and 76.0%, respectively (P = 0.784). The best assessment parameter of these risk scores was their negative predictive value: 99.1% and 99.0% for the complete and laboratory-free, respectively. CONCLUSIONS: The developed risk scores showed a moderate performance as a screening test. People with a score of ≥ 2 points should undergo further testing to rule out CKD. Using the laboratory-free risk score is a practical approach in developing countries where laboratories are not readily available and undiagnosed CKD has significant morbidity and mortality.

Depressive symptoms and carotid intima-media thickness in South American Hispanics: results from the PREVENCION study.

This study aimed to: (1) examine the relationship between depressive symptoms and subclinical atherosclerosis, measured by carotid intima-media thickness (IMT); and, (2) Determine the moderating effect of gender in this relationship among South American Hispanics. We studied 496 adults enrolled in the population-based PREVENCION study. Carotid IMT was measured with high-resolution ultrasonography. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale. Mean carotid IMT was 0.66 mm. (SD = 0.17) and mean depression score was 5.6 (SD = 3.5). Depressive symptoms were not associated with carotid IMT (ß = 0.04, p = 0.222) in multivariate analyses. A significant moderating effect of gender was found (ß for interaction = 0.10, p = 0.030), resulting from a significant association between depressive symptoms and carotid IMT in men but not women. Depressive symptoms were associated with subclinical atherosclerosis in South American Hispanic men but not women after controlling for demographic characteristics and traditional cardiovascular risk factors.

Influence of altitude on hypertension phenotypes and responses to antihypertensive therapy: Review of the literature and design of the INTERVENCION trial.

Systemic arterial hypertension constitutes the leading cause of mortality worldwide, and affects people living at different altitudes above sea level (AASL). AASL has a major impact on cardiovascular function and various biologic pathways that regulate blood pressure-related phenotypes, but whether it affects the clinical response to antihypertensive therapy is unknown. The hemodynamic adaptations observed among lowlanders acutely exposed to high altitude (HA) is distinct from those observed among HA dwellers. However, the phenotypic patterns of hypertension and the response to standard antihypertensive agents among adults chronically exposed to different AASL are poorly understood. The authors describe the protocol for the INTERVENCION trial, a randomized clinical trial designed to assess the effects of three first-line antihypertensive monotherapies (a thiazide diuretic, an angiotensin receptor blocker, and a calcium channel blocker) on peripheral and central blood pressure, in-office blood pressure, and ambulatory blood pressure hemodynamics of hypertensive patients living at different AASL (low altitude, intermediate altitude, and high altitude). The primary end point is the reduction in 24-hour brachial systolic blood pressure. The INTERVENCION trial will provide the first clinical trial data regarding the influence of AASL on the response to antihypertensive monotherapy, as well as the hemodynamic characteristics of arterial hypertension at different AASL.

Urbanization and Altitude Are Associated with Low Kidney Function in Peru.

Background: Kidney health needs to be studied in low- and middle-income countries with populations living at high altitude and undergoing urbanization. We studied whether greater level of urbanization was associated with worse kidney function and higher hemoglobin was associated with worse kidney function at high altitude. Methods: Cross-sectional analysis of population-based studies in Peru including five sites at different altitude above the sea level and urbanization level (in decreasing order of urbanization): Lima (sea level), Arequipa (2335 m), urban Puno (3825 m), Tumbes (sea level), and rural Puno (3825 m). The exposures were urbanization and altitude as per study site, and hemoglobin (g/dL). The outcome was the estimated glomerular filtration rate (eGFR). Results: Four thousand two hundred eight people were studied: mean age was 57.4 years (standard deviation: 12.4) and 51.9% were women. In comparison to rural Puno, eGFR was similar in Lima; in comparison to rural Puno, Arequipa, urban Puno, and Tumbes had worse eGFR, for example, in Arequipa, ß = -8.07 (95% confidence interval [CI]: -10.90 to -5.24). Intermediate (ß = -8.60; 95% CI: -10.55 to -6.66) and high (ß = -11.21; 95% CI: -14.19 to -8.24) altitude were negatively correlated with eGFR when only urban places were analyzed. At high altitude, there was a trend for a negative association between hemoglobin and eGFR: ß = -1.09 (95% CI: -2.22 to 0.04). Conclusions: Apparently, higher altitude and level of urbanization, except for one highly urbanized site, were associated with worse kidney function. Our findings suggest that some of the adverse impact of high altitude on kidney function has been balanced by the lower risk conferred by rural environments.

Hemodynamic Patterns Identified by Impedance Cardiography Predict Mortality in the General Population: The PREVENCION Study.

Background Blood pressure is determined by the interactions between the heart and arterial properties, and subjects with identical blood pressure may have substantially different hemodynamic determinants. Whether arterial hemodynamic indices quantified by impedance cardiography ( ICG ), a simple operator-independent office procedure, independently predict all-cause mortality in adults from the general population, and specifically among those who do not meet criteria for American College of Cardiology/American Heart Association stage 2 hypertension, is currently unknown. Methods and Results We studied 1639 adults aged 18 to 80 years from the general population. We used ICG to measure hemodynamic parameters and metrics of cardiac function. We assessed the relationship between hemodynamic parameters measured at baseline and all-cause mortality over a mean follow-up of 10.9 years. Several ICG parameters predicted death. The strongest predictors were total arterial compliance index (standardized hazard ratio=0.38; 95% confidence interval=0.31-0.46; P<0.0001) and indices of cardiac contractility: velocity index (standardized hazard ratio=0.45; 95% confidence interval=0.37-0.55; P<0.0001) and acceleration index (standardized hazard ratio=0.44; 95% confidence interval=0.35-0.55; P<0.0001). These remained independently predictive of death after adjustment for multiple confounders, as well as systolic and diastolic blood pressure. Among subjects without stage 2 hypertension (n=1563), indices of cardiac contractility were independently predictive of death and identified a subpopulation (25% of non-stage-2 hypertensives) that demonstrated a high 10-year mortality risk, equivalent to that of stage 2 hypertensives. Conclusions Hemodynamic patterns identified by ICG independently predict mortality in the general population. The predictive value of ICG applies even in the absence of American College of Cardiology/American Heart Association stage 2 hypertension and identifies higher-risk individuals who are in earlier stages of the hypertension continuum.

Prevalence of the metabolic syndrome in Peruvian Andean hispanics: the PREVENCION study.

Data regarding the prevalence of metabolic syndrome (MTS) in Andean populations are limited. We evaluated the prevalence of MTS according to American Heart Association/National Heart, Lung and Blood Institute criteria among 1878 subjects in the PREVENCION study in Peru. In women, the most common component was low HDL cholesterol (60.9%) followed by abdominal obesity (36.9%). In men, the most common component was elevated triglycerides (52.0%) followed by low HDL cholesterol (32.5%), whereas the prevalence of abdominal obesity was 14%. Abnormal fasting glucose was the least common component in men (5.4%) and women (5.0%). The prevalence of MTS was significantly higher in women compared to men (23.2% versus 14.3%) and increased steeply with age, particularly in women (p<0.0001). Using body mass index (BMI>or=30kg/m2) instead of waist circumference as a component of the MTS lead to equivalent prevalence estimates of MTS in men but significantly underestimated the prevalence in women. The MTS is highly prevalent among Peruvian Andeans, particularly in older women. The pattern of MTS components in this Andean population is characterized by a high prevalence of dyslipidemia and a relatively low prevalence of elevated fasting glucose. Further studies are required to characterize genetic and environmental determinants of these patterns.

Design of PREVENCION: a population-based study of cardiovascular disease in Peru.

Latin America is undergoing the epidemiologic transition that occurred earlier in developed countries, and is likely to face a gigantic epidemic of heart disease in the next few years unless urgent action is taken. The first essential component of any effective cardiovascular disease (CVD) control program is to establish reliable estimates of cardiovascular disease-related morbidity and mortality. However, such data from population-based studies in Latin America are still lacking. In this paper, we present the design and operation of PREVENCION (Estudio Peruano de Prevalencia de Enfermedades Cardiovasculares, for Peruvian Study of the Prevalence of Cardiovascular diseases). PREVENCION is an ongoing population-based study on a representative sample of the civilian non-institutionalized population of the second largest city in Peru. Its population is comparable to the rest of the Peruvian urban population and closely resembles other Latin American populations in countries such as Bolivia and Ecuador. Our study will contribute to the enormous task of understanding and preventing CVD in Latin America.

Prospective risk factors for increased central augmentation index in men and women.

BACKGROUND: Arterial wave reflections are important determinants of central pressure pulsatility and left ventricular afterload. The augmentation index (AIx) is the most widely used surrogate of arterial wave reflections. Despite multiple cross-sectional studies assessing the correlates of AIx, little prospective data exist regarding changes in AIx over time. We aimed to assess the predictors of changes in AIx over time in adults from the general population. METHODS: We performed radial arterial tonometry assessments a median of 3.18 ± 0.4 years apart on 143 nondiabetic adult participants in the population-based PREVENCION study. Central AIx was obtained using the generalized transfer function of the Sphygmocor device. RESULTS: Predictors of the change in AIx over time were investigated. Among men (n = 67), the change in AIx was predicted by abdominal obesity (standardized ß for waist circumference = 0.34; P = 0.002), impaired fasting glucose (standardized ß = 0.24; P = 0.009), and the change in heart rate (standardized ß = -0.78; P < 0.001). Among women (n = 76), the change in AIx was predicted by non-high-density lipoprotein cholesterol (standardized ß = 0.33; P = 0.001), C-reactive protein levels (standardized ß = 0.24; P = 0.02), change in mean arterial pressure (standardized ß = 0.33; P = 0.001), and change in heart rate (standardized ß = -0.52; P < 0.001). CONCLUSIONS: Metabolic and inflammatory factors predicted changes in AIx over time, with important sex differences. Metabolic factors, such as abdominal obesity and impaired fasting glucose, predicted changes in AIx in men, whereas C-reactive protein and non-high-density lipoprotein cholesterol levels predicted changes in women. Our findings highlight the impact of sex on arterial properties and may guide the design of interventions to favorably impact changes in late systolic pressure augmentation.

Metabolic syndrome as an underlying disease entity and its relationship to subclinical atherosclerosis in Andean Hispanics.

BACKGROUND: The question of whether the metabolic syndrome truly reflects a single disease entity with a common underlying pathology remains unclear. In this study, we assess whether metabolic syndrome represents an underlying disease construct in a large population-based sample of Andean Hispanic adults and examine its relationship to subclinical atherosclerosis. METHODS: The study sample was comprised of 2513 participants. Confirmatory factor analysis (CFA) was used to identify a metabolic syndrome latent factor using waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), and glucose levels as indicators. The relationship with subclinical atherosclerosis, measured by carotid intima media thickness (cIMT), was assessed using structural equation modeling. RESULTS: Results supported the proposed structure of the metabolic syndrome latent factor evidenced by adequate fit indexes. HDL-C did not significantly load on the metabolic syndrome latent factor (standardized factor loading=0.01, P=0.88). The metabolic syndrome latent factor was significantly associated with cIMT in women (B=0.007, P<0.001) and men (B=0.008, P<0.001) after controlling for age, low-density lipoprotein cholesterol and smoking. CONCLUSIONS: Our findings suggest that metabolic syndrome components, such as waist circumference, blood pressure, TGs, and glucose levels, but not HDL-C, share a common underlying pathophysiology that may contribute to the progression of atherosclerosis in Andean Hispanics. Its longitudinal association with cardiovascular disease should be the focus of future research.

Metabolic syndrome in andean populations.

The metabolic syndrome, a cluster of metabolic abnormalities, has been linked to both cardiovascular disease and type 2 diabetes mellitus risk. Several studies have shown that ethnicity is an important determinant for risk of developing the metabolic syndrome; therefore, further understanding of the prevalence and presentation of the metabolic syndrome in various ethnic groups is needed. Latin American communities, and particularly Andean countries, are largely understudied in relation to the metabolic syndrome and until recently, the prevalence of this metabolic disturbance in Andean Hispanics was unknown. Nonetheless, recent (and ongoing) population studies are providing important data regarding the prevalence and patterns of the metabolic syndrome in various Andean countries. This review aims to summarize and interpret the information provided by these studies in an effort to better characterize the metabolic syndrome in Andean Hispanics.

A 'polypill' aimed at preventing cardiovascular disease could prove highly cost-effective for use in Latin America.

We evaluated the cost-effectiveness of administering a daily "polypill" consisting of three antihypertensive drugs, a statin, and aspirin to prevent cardiovascular disease among high-risk patients in Latin America. We found that the lifetime risk of cardiovascular disease could be reduced by 15 percent in women and by 21 percent in men if the polypill were used by people with a risk of cardiovascular disease equal to or greater than 15 percent over ten years. Attaining this goal would require treating 26 percent of the population at a cost of $34-$36 per quality-adjusted life-year. Offering the polypill to women at high risk and to men age fifty-five or older would be the best approach and would yield acceptable incremental cost-effectiveness ratios. The polypill would be very cost-effective even in the country with the lowest gross national income in our study. However, policy makers must weigh the value of intervention with the polypill against other interventions, as well as their country's willingness and ability to pay for the intervention.

Major cardiovascular risk factors in Latin America: a comparison with the United States. The Latin American Consortium of Studies in Obesity (LASO).

BACKGROUND: Limited knowledge on the prevalence and distribution of risk factors impairs the planning and implementation of cardiovascular prevention programs in the Latin American and Caribbean (LAC) region. METHODS AND FINDINGS: Prevalence of hypertension, diabetes mellitus, abnormal lipoprotein levels, obesity, and smoking were estimated from individual-level patient data pooled from population-based surveys (1998-2007, n=31,009) from eight LAC countries and from a national survey of the United States (US) population (1999-2004) Age and gender specific prevalence were estimated and age-gender adjusted comparisons between both populations were conducted. Prevalence of diabetes mellitus, hypertension, and low high-density lipoprotein (HDL)-cholesterol in LAC were 5% (95% confidence interval [95% CI]: 3.4, 7.9), 20.2% (95% CI: 12.5, 31), and 53.3% (95% CI: 47, 63.4), respectively. Compared to LAC region's average, the prevalence of each risk factor tended to be lower in Peru and higher in Chile. LAC women had higher prevalence of obesity and low HDL-cholesterol than men. Obesity, hypercholesterolemia, and hypertriglyceridemia were more prevalent in the US population than in LAC population (31 vs. 16.1%, 16.8 vs. 8.9%, and 36.2 vs. 26.5%, respectively). However, the prevalence of low HDL-cholesterol was higher in LAC than in the US (53.3 vs. 33.7%). CONCLUSIONS: Major cardiovascular risk factors are highly prevalent in LAC region, in particular low HDL-cholesterol. In addition, marked differences do exist in this prevalence profile between LAC and the US. The observed patterns of obesity-related risk factors and their current and future impact on the burden of cardiovascular diseases remain to be explained.

Ethnic differences in arterial wave reflections and normative equations for augmentation index.

Data regarding ethnic differences in wave reflections, which markedly affect the central pressure profile, are very limited. Furthermore, because age, heart rate, and body height are strong determinants of augmentation index, relating single measurements to normative data (in which augmentation index values correspond with average population values of its determinants) is challenging. We studied subject-level data from 10 550 adults enrolled in large population-based studies. In a healthy reference sample (n=3497), we assessed ethnic differences in augmentation index (ratio of second/first systolic peaks) and generated equations for adjusted z scores, allowing for a standardized comparison between individual augmentation index measurements and the normative population mean from subjects of the same age, sex, ethnic population, body height, and heart rate. After adjustment for age, body height, heart rate, and mean arterial pressure, African blacks (women: 154%; men: 138%) and Andean Hispanics (women: 152%; men: 133%) demonstrated higher central (aortic) augmentation index values than British whites (women: 140%; men: 128%), whereas American Indians (women: 133%; men: 122%) demonstrated lower augmentation index (all P<0.0001), without significant differences between Chinese and British whites. Similar results were found for radial augmentation index. Nonlinear ethnic/sex-specific equations for z scores were successfully generated to adjust individual augmentation index values for age, body height, and heart rate. Marked ethnic differences in augmentation index exist, which may contribute to ethnic differences in hypertensive organ damage. Our study provides normative data that can be used to complement the interpretation of individual hemodynamic assessments among men and women of various ethnic populations, after removing the effect of various physiological determinants.

Optimal definitions for abdominal obesity and the metabolic syndrome in Andean Hispanics: the PREVENCION study.

OBJECTIVE: We aimed to establish optimal definitions for abdominal obesity and metabolic syndrome (MetS) among Andean adults. RESEARCH DESIGN AND METHODS: Among 1,448 Andean adults, we assessed the relationship between waist circumference and subclinical vascular disease assessed by carotid intima-media thickness (cIMT) and manifest cardiovascular disease (M-CVD). RESULTS: Optimal waist circumference cutoffs to classify individuals with abnormal cIMT or M-CVD were >97 and >87 cm in men and women, respectively. With these cutoffs, there was substantial disagreement between the original American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and the recently updated MetS definition, particularly among men (kappa = 0.85). Subjects with MetS identified by the updated definition but not meeting the original AHA/NHLBI MetS criteria demonstrated significantly increased cIMT (P < 0.001) compared with subjects who did not meet the MetS criteria by either definition. CONCLUSIONS: Our findings support the use of ethnic-specific waist circumference cutoffs and the updated MetS definition in Andean adults.

Normative values and correlates of carotid artery intima-media thickness and carotid atherosclerosis in Andean-Hispanics: The Prevencion Study.

OBJECTIVES: Carotid intima-media thickness (cIMT) is an independent predictor of cardiovascular risk. Furthermore, ethnicity and gender-specific normative data are required to assess cIMT, which are not available for Andean-Hispanics. In addition, data regarding correlates of subclinical atherosclerosis in ethnic population are needed. METHODS: We studied 1448 adults enrolled in a population-based study in Peru. cIMT and carotid plaque were measured with high-resolution ultrasonography. A healthy reference sample (n=472) with no cardiovascular disease, normal weight and normal metabolic parameters was selected to establish normative cIMT values. Correlates of abnormal cIMT and carotid plaque were assessed in the entire population. RESULTS: In the reference sample, 95th-percentile cIMT values were both age and gender-dependent. In stepwise regression, selected predictors of increasing cIMT were: older age, impaired fasting glucose, diabetes mellitus, higher systolic blood pressure, higher LDL-cholesterol, smoking and male gender. Predictors of carotid plaque included older age, male gender, higher systolic blood pressure, lower diastolic blood pressure and higher LDL-cholesterol. HDL-cholesterol and C-reactive protein were not associated with cIMT or carotid plaque. The lack of association with HDL-cholesterol was confirmed using high performance liquid chromatography. CONCLUSIONS: We present ethnic-specific cut-offs for abnormal cIMT applicable to Andean-Hispanics and correlates of subclinical atherosclerosis in this population. Pending longitudinal studies, our data supports several risk associations seen in other populations and can be used to identify Andean-Hispanics at increased risk for atherosclerotic cardiovascular disease. The lack of association between HDL-C and cIMT or carotid plaque in this population requires further investigation.

Prevalence of lifestyle-related cardiovascular risk factors in Peru: the PREVENCION study.

OBJECTIVES: To estimate the prevalence of lifestyle-related cardiovascular risk factors in the adult population of Arequipa, the second largest city in Peru. METHODS: The prevalence and patterns of smoking, alcohol drinking, lack of physical activity, high-fat diet, and low fruit and vegetable intake were evaluated among 1 878 subjects (867 men and 1 011 women) in a population-based study. RESULTS: The age-standardized prevalence of current smoking, former smoking, and never smoking were 21.6%, 14.3%, and 64.1%, respectively. The prevalence of current smoking was significantly higher in men than women (31.1% vs. 12.1%; P < 0.01). The prevalence of current alcohol use was 37.7% and significantly higher in men than women (55.5% vs. 19.7%; P < 0.01). Similarly, the prevalence of binge drinking was 21.2%, and the percentage of men who binge drink (36.1%) was significantly higher than for women (6.4%; P < 0.01). The vast majority of alcohol drinkers reported a pattern of alcohol consumption mainly on weekends and holidays rather than regular drinking with meals during the week. The proportion of insufficiently active people was 57.6% and was significantly higher in women than men (63.3% vs. 51.9%; P < 0.01). Overall, 42.0% of adults reported consuming high-fat diets, 34.5% reported low fruit intake, and 33.3% reported low vegetable intake. CONCLUSIONS: The high prevalence of lifestyle-related cardiovascular risk factors found in this Andean population is of concern. Preventive programs are urgently needed to deal with this growing problem.

Endogenous nitric oxide synthase inhibitors, arterial hemodynamics, and subclinical vascular disease: the PREVENCION Study.

Endogenous NO synthase inhibitors (end-NOSIs) have been associated with cardiovascular risk factors and atherosclerosis. In addition, end-NOSIs may directly cause hypertension through hemodynamic effects. We aimed to examine the association between end-NOSI asymmetrical dimethylarginine (ADMA) and N-guanidino-monomethyl-arginine (NMMA), subclinical atherosclerosis, and arterial hemodynamics. We studied 922 adults participating in a population-based study (PREVENCION Study) and examined the correlation between end-NOSI/L-arginine and arterial hemodynamics, carotid-femoral pulse wave velocity, and carotid intima-media thickness using linear regression. ADMA, NMMA, and L-arginine were found to be differentially associated with various classic cardiovascular risk factors. ADMA and NMMA (but not L-arginine) were significant predictors of carotid intima-media thickness, even after adjustment for cardiovascular risk factors, C-reactive protein, and renal function. In contrast, ADMA and NMMA did not predict carotid-femoral pulse wave velocity, blood pressure, or hemodynamic abnormalities. Higher L-arginine independently predicted systolic hypertension, higher central pulse pressure, incident wave amplitude, central augmented pressure, and lower total arterial compliance but not systemic vascular resistance or cardiac output. We conclude that ADMA and NMMA are differentially associated with cardiovascular risk factors, but both end-NOSIs are independent predictors of carotid atherosclerosis. In contrast, they are not associated with large artery stiffness, hypertension, or hemodynamic abnormalities. Our findings are consistent with a role for asymmetrical arginine methylation in atherosclerosis but not in large artery stiffening, hypertension, or long-term hemodynamic regulation. L-arginine is independently associated with abnormal pulsatile (but not resistive) arterial hemodynamic indices, which may reflect abnormal L-arginine transport, leading to decreased intracellular bioavailability for NO synthesis.