Exploring food insecurity and obesity in Dutch disadvantaged neighborhoods: a cross-sectional mediation analysis.

BACKGROUND: Food insecurity is related to risk of adverse health outcomes such as obesity, but the explanatory factors underlying this association are still unclear. This study aimed to assess the association between food insecurity and obesity, and to explore potential mediation by sociodemographic and lifestyle factors. METHODS: This cross-sectional study was conducted among 250 participants in a deprived urban area in the Netherlands. Data on sociodemographic and lifestyle factors, food insecurity status and diet quality were collected using questionnaires. Diet quality was determined based on current national dietary guidelines. BMI was calculated from self-reported height and weight. Regression analyses were performed to explore the association between food insecurity and BMI status. Mediation analyses were performed to estimate the total-, direct-, and indirect effect and proportion of total effect mediated of the food insecurity-obesity association. RESULTS: The overall prevalence of food insecurity was 26%. Food insecurity was associated with obesity (OR = 2.49, 95%CI = 1.16, 5.33), but not with overweight (OR = 1.15, 95%CI = 0.54, 2.45) in the unadjusted model. The food insecurity-obesity association was partially mediated by living situation (proportion mediated: 15.4%), diet quality (- 18.6%), and smoking status (- 15.8%) after adjustment for other covariates. CONCLUSIONS: The findings of this study suggest an association between food insecurity and obesity. Living situation, diet quality and smoking status explained part, but not all, of the total association between food insecurity and obesity. Future longitudinal studies are warranted to examine the temporal order of the food insecurity-obesity association and potential mediators in this relationship. In addition, food insecurity and its potential consequences need to be taken into account in obesity prevention programs and policies.

Introducing the importance and difficulties of a three-step approach to improve nonadherence to antihypertensive drugs: a case series.

Nonadherence to antihypertensive drugs is an important reason for not reaching blood pressure goals. A possible method to improve nonadherence involves three essential steps: identification of nonadherent patients (step 1), determination of underlying causes (step 2) and a personalized solution (step 3). We present three unique cases to show the importance and difficulties of this three-step approach. Patients participated in a randomized controlled trial to improve nonadherence to antihypertensive drugs (RHYME-RCT, Dutch Trial Register NL6736). Drug level measurements were used to identify nonadherence to antihypertensive drugs and communication on drug levels was supported by a tailored feedback tool in these patients. These cases showed that a three-step approach of identifying nonadherence and determination of the underlying cause, can lead to a personalized solution to improve therapy even when nonadherence was excluded. Open communication with patients remains an essential part when improving nonadherence.

Successes and disappointments with clinical islet transplantation.

Transplantation of pancreatic islets is considered a therapeutic option for patients with type 1 diabetes mellitus who have life-threatening hypoglycaemic episodes. After the procedure, a decrease in the frequency and severity of hypoglycaemic episodes and sustained graft function as indicated by detectable levels of C-peptide can be seen in the majority of patients. However, true insulin independence, if achieved, usually lasts for at most a few years. Apart from the low insulin independence rates, reasons for concern regarding this procedure are the side effects of the immunosuppressive therapy, allo-immunization, and the high costs. Moreover, whether islet transplantation prevents the progression of diabetic micro- and macrovascular complications is largely unknown. Areas of current research include the development of less toxic immunosuppressive regimens, the control of the inflammatory reaction immediately after transplantation, the identification of the optimal anatomical site for islet infusion, and the possibility to encapsulate transplanted islets to protect them from the allo-immune response. At present, pancreatic islet transplantation is still an experimental procedure, which is only indicated for a highly selected group of type 1 diabetic patients with life-threatening hypoglycaemic episodes.

Agreement between measurement of 25-hydroxyvitamin D3 in dried blood spot samples and serum in a Chinese population in the Netherlands.

Blood for determining 25-hydroxyvitamin D3 [25(OH)D3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this proof-of-concept study was to investigate levels of agreement between measurements of 25(OH)D3 obtained with DBS compared with serum. 301 Chinese participants were included who completed 25(OH)D3 measurement from DBS and from simultaneously collected blood samples obtained by venipuncture. Measurements of both DBS and serum 25(OH)D3 were performed using liquid chromatography followed by tandem mass spectrometry. Agreement between the two methods was assessed with Passing and Bablok regression analysis and Bland-Altman plot. Measurements showed a good correlation (Pearson's correlation coefficient r = 0.929, P < 0.001) between the two methods. After recalculating for a 13% difference, a regression equation of DBS 25(OH)D3 = -1.91 + 1.00 serum 25(OH)D3 was found in Passing and Bablok regression analysis. Bland-Altman analysis showed a fixed bias of 1.7 nmol/L; upper and lower limit of agreement was 24.1 nmol/L and -20.7 nmol/L, respectively. Sensitivity of recalculated DBS for 25(OH)D3 concentrations <30 and <50 nmol/L was 87.8% and 91.1%, respectively, and specificity was 89.2% and 83.1%, respectively. In conclusion, a good agreement was found between the measurement of 25(OH)D3 obtained with DBS compared with serum. DBS may possibly be used in a future screening program, but it is less suitable for individualized vitamin D status assessment.

Fatty fish and supplements are the greatest modifiable contributors to the serum 25-hydroxyvitamin D concentration in a multiethnic population.

OBJECTIVE: Because vitamin D synthesis is lower in a heavily pigmented skin than in a lighter skin, the relative contribution of determinants to the vitamin D concentration might differ between ethnic groups. The aim of this study was to assess the prevalence of vitamin D deficiency and the relative contribution of vitamin D consumption and exposure to sunlight to the vitamin D concentration in a multiethnic population. DESIGN: Cross-sectional study. PATIENTS: A total of 613 adults aged 18-65 years from a random sample from general practices in the Netherlands (52 degrees N, 2003-05), stratified according to gender and ethnic group. MEASUREMENTS: Serum 25-hydroxyvitamin D [25(OH)D], PTH, ethnic group, sunlight exposure, consumption of foods and supplements rich in vitamin D. RESULTS: The prevalence (95% confidence interval) of vitamin D deficiency [serum 25(OH)D < 25 nmol/l] was higher in Turkish (41.3%; 32.5-50.1), Moroccan (36.5%; 26.9-46.1), Surinam South Asian (51.4%; 41.9-60.9), Surinam Creole (45.3%; 34.0-56.6), sub-Saharan African (19.3%; 9.1-29.5) and other adults (29.1%; 17.1-41.1) compared to the indigenous Dutch (5.9%; 1.3-10.5). Modifiable, significant determinants (standardized regression coefficients) for serum 25(OH)D concentration were: consumption of fatty fish (0.160), use of vitamin D supplements (0.142), area of uncovered skin (highest category 0.136; middle category 0.028), use of tanning bed (0.103), consumption of margarine (0.093) and preference for sun (0.089). We found no significant modification of ethnic group on the effect of sunlight determinants. CONCLUSION: Of the modifiable determinants, fatty fish and supplements are the greatest contributors to the serum 25(OH)D concentration in a multiethnic population.

Lipoprotein-associated phospholipase A2 and measures of extracoronary atherosclerosis: the Rotterdam Study.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may be a new and independent predictor of cardiovascular events. The effect of Lp-PLA2 may be exerted through effects of the enzyme on the development of atherosclerosis. Therefore, we investigated the association between Lp-PLA2 activity and measures of extracoronary atherosclerosis. METHODS AND RESULTS: Lp-PLA2 activity was determined in a random sample of 1820 participants from the Rotterdam Study, a population-based cohort study in men and women > or =55 years. Common carotid intima-media thickness, carotid plaques, ankle-arm index, and aortic calcification were examined. Atherosclerosis status could be assigned in 1609 participants. The age-adjusted odds ratio of having atherosclerosis at any site for the highest versus the lowest tertile of Lp-PLA2 activity was 1.86 (95% CI, 1.01 to 3.43) in men and 1.60 (95% CI, 1.08 to 2.37) in women. After additional adjustment for cholesterol, these associations attenuated or even disappeared. The odds ratios of having atherosclerosis at specific sites (carotid arteries and aortic-iliac-femoral tract) followed a similar pattern. CONCLUSIONS: Although Lp-PLA2 has been found to be independently associated with cardiovascular events, the association with measures of subclinical extracoronary atherosclerosis found in this study strongly attenuated or even disappeared after adjustment for cholesterol.

Improvement of radiocephalic fistula maturation: rationale and design of the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study - a randomized controlled trial.

BACKGROUND: Non-maturation is a frequent complication of radiocephalic arteriovenous fistulas (RCAVF). In an animal model, liposomal prednisolone improved maturation of experimental fistulas. The Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study investigates if liposomal prednisolone improves RCAVF maturation. METHODS AND RESULTS: The LIPMAT study is an investigator-initiated, multicenter, double-blinded, placebo-controlled randomized controlled trial with 1:1 randomization to liposomal prednisolone or placebo. Eighty patients receiving an RCAVF will be included. The primary outcome is the cephalic vein diameter six weeks after surgery, measured by ultrasound. The LIPMAT study started in May 2016. Enrollment is expected to be completed by the end of 2017. CONCLUSIONS: The LIPMAT study is the first to evaluate the efficacy of liposomal prednisolone to enhance RCAVF maturation.

Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory marker of cardiovascular disease. In the present study, we investigated whether Lp-PLA2 is an independent predictor of coronary heart disease and ischemic stroke. METHODS AND RESULTS: The Rotterdam Study is a population-based follow-up study in 7983 subjects > or =55 years of age. We performed a case-cohort study, including 308 coronary heart disease cases, 110 ischemic stroke cases, and a random sample of 1820 subjects. We used Cox proportional-hazard models with modification of the standard errors based on robust variance estimates to compute hazard ratios adjusted for age, sex, body mass index, systolic blood pressure, non-HDL cholesterol, HDL cholesterol, diabetes, smoking, alcohol consumption, cholesterol-lowering medication, white blood cell count, and C-reactive protein. Compared with the first quartile of Lp-PLA2 activity, multivariate-adjusted hazard ratios for coronary heart disease for the second, third, and fourth quartiles were 1.39 (95% CI, 0.92 to 2.10), 1.99 (95% CI, 1.32 to 3.00), and 1.97 (95% CI, 1.28 to 3.02), respectively (P for trend=0.01). Corresponding multivariate-adjusted hazard ratios for ischemic stroke were 1.08 (95% CI, 0.55 to 2.11), 1.58 (95% CI, 0.82 to 3.04), and 1.97 (95% CI, 1.03 to 3.79) (P for trend=0.03). The relation between Lp-PLA2 and coronary heart disease was present in both subjects with non-HDL cholesterol levels below the median and those with non-HDL cholesterol levels above the median. CONCLUSIONS: This study shows that Lp-PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population.

High prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, Netherlands.

BACKGROUND: Vitamin D deficiency is common in dark-skinned persons living in northern countries. Vitamin D deficiency during pregnancy may have serious consequences for both mother and child. OBJECTIVE: The objective was to ascertain the prevalence of vitamin D deficiency in pregnant women of several ethnic backgrounds who were living in The Hague, a large city in the Netherlands. DESIGN: Midwives whose practice was visited by a large number of non-Western immigrants added the assessment of serum 25-hydroxyvitamin D [25(OH)D] to the standard blood test given to women who visited the practice during week 12 of pregnancy. Subsequently, the Municipal Health Service collected additional data from the midwives' files (June 2002 through March 2004): background variables, use of tobacco or alcohol or drugs, and infectious diseases. The women were grouped ethnically as Western, Turkish, Moroccan, and other non-Western. RESULTS: The vitamin D concentrations of 358 women were found in the midwives' files. Of these women, 29% were Western, 22% were Turkish, and 19% were Moroccan. Mean serum 25(OH)D concentrations in Turkish (15.2 +/- 12.1 nmol/L), Moroccan (20.1 +/- 13.5 nmol/L), and other non-Western women (26.3 +/- 25.9 nmol/L) were significantly (P

Soluble Fas, a mediator of apoptosis, C-reactive protein, and coronary and extracoronary atherosclerosis. The Rotterdam Coronary Calcification Study.

RATIONALE: Findings from laboratory studies strongly suggest a role for apoptosis, the process of programmed cell death, in cardiovascular disease. No population-based study has yet investigated whether serum levels of soluble forms of Fas, a receptor capable of inducing the apoptosis cascade, are associated with coronary and extracoronary atherosclerosis. METHODS: Within the Rotterdam Coronary Calcification Study, a population-based cohort study, we measured coronary calcification using electron-beam computed tomography, abdominal aortic calcification by abdominal X-ray, carotid plaques and common carotid intima-media thickness (IMT) by ultrasonography, and lower extremity atherosclerosis by computation of the ankle-arm index. Levels of sFas and of the inflammatory mediator C-reactive protein (CRP) were measured in 1036 participants. RESULTS: Levels of sFas were not related to coronary or extracoronary atherosclerosis. CRP showed strong associations with measures of atherosclerosis, including coronary atherosclerosis, which largely remained after adjustment for traditional cardiovascular risk factors. CONCLUSION: The results of this study do not support a role for sFas in the identification of subjects with atherosclerosis.

Vitamin D status in the Chinese population in the Netherlands: The DRAGON study.

INTRODUCTION: Vitamin D is essential for bone health since it stimulates the intestinal absorption of calcium and phosphorus from the gut, both necessary for bone mineralization. However, vitamin D deficiency is highly prevalent among several non-Western immigrant populations in the Netherlands. To date, there are no data available of the vitamin D status in the Chinese population residing in the Netherlands. Therefore, an observational study was performed to determine 25-hydroxyvitamin D (25(OH)D) concentrations and to assess potential determinants of low vitamin D status. METHODS: Subjects, aged 18 years and older, with a Chinese background and residing in the Netherlands were invited to participate in the study. A questionnaire was used to assess general characteristics and lifestyle habits. Fasting blood samples were obtained in March 2014 to measure serum 25(OH)D concentration, and analysed by liquid chromatography tandem mass spectrometry. RESULTS: 418 subjects participated in the study, 104 men and 314 women. The mean age for both men and women was 56 years. Serum 25(OH)D concentration <50nmol/L was more prevalent in men than in women (67.9% and 53.1%, respectively; p=0.008). The percentage of serum 25(OH)D concentration<25nmol/L in men and women was 5.8% and 10.9%, respectively. Multiple logistic regression analysis, adjusted for age and gender, revealed that non-use of vitamin D supplements and fewer days per week of physical activity were significant predictors of serum 25(OH)D levels below 50nmol/L. CONCLUSIONS: Within the Chinese population living in the Netherlands, serum 25(OH)D concentration was below 50nmol/L in 68% of men and 53% of women. Use of vitamin D supplements by Chinese people in the Netherlands was highly protective against low 25(OH)D levels.

Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study.

BACKGROUND: Several noninvasive methods are available to investigate the severity of extracoronary atherosclerotic disease. No population-based study has yet examined whether differences exist between these measures with regard to their predictive value for myocardial infarction (MI) or whether a given measure of atherosclerosis has predictive value independently of the other measures. METHODS AND RESULTS: At the baseline (1990-1993) examination of the Rotterdam Study, a population-based cohort study among subjects age > or =55 years, carotid plaques and intima-media thickness (IMT) were measured by ultrasound, abdominal aortic atherosclerosis by x-ray, and lower-extremity atherosclerosis by computation of the ankle-arm index. In the present study, 6389 subjects were included; 258 cases of incident MI occurred before January 1, 2000. All 4 measures of atherosclerosis were good predictors of MI independently of traditional cardiovascular risk factors. Hazard ratios were equally high for carotid plaques (1.83 [1.27 to 2.62], severe versus no atherosclerosis), carotid IMT (1.95 [1.19 to 3.19]), and aortic atherosclerosis (1.94 [1.30 to 2.90]) and slightly lower for lower-extremity atherosclerosis (1.59 [1.05 to 2.39]), although differences were small. The hazard ratio for MI for subjects with severe atherosclerosis according to a composite atherosclerosis score was 2.77 (1.70 to 4.52) compared with subjects with no atherosclerosis. The predictive value of MI for a given measure of atherosclerosis was independent of the other atherosclerosis measures. CONCLUSIONS: Noninvasive measures of extracoronary atherosclerosis are strong predictors of MI. The relatively crude measures directly assessing plaques in the carotid artery and abdominal aorta predict MI equally well as the more precisely measured carotid IMT.

Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study.

Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion molecules were assessed in a subsample of 714 participants. In multivariate analyses, logarithmically transformed CRP (regression coefficient [beta]=-0.023, 95% CI -0.033 to -0.012) and IL-6 (beta=-0.025, 95% CI -0.049 to -0.001) were inversely associated with the ankle-arm index. Only CRP was associated with carotid intima-media thickness (beta=0.018, 95% CI 0.010 to 0.027). Compared with the lowest tertile, the odds ratio for moderate to severe carotid plaques associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest tertile]). Soluble vascular cell adhesion molecule-1 was not significantly associated with any of the measures of atherosclerosis. This study indicates that CRP is associated with the severity of atherosclerosis measured at various sites. Associations of the other markers with atherosclerosis were less consistent.

Evaluation of plasma lactate as a parameter for disease severity on admission in travelers with Plasmodium falciparum malaria.

BACKGROUND: Rapid immunochromatographic dipstick assays are used increasingly in many tropical and Western countries as a tool to diagnose Plasmodium falciparum malaria. However, these tests do not provide any information about the severity of the infection. We evaluated the usefulness of plasma lactate as a parameter for disease severity on admission in imported P. falciparum malaria. METHODS: In a cohort of 61 nonimmune travelers with imported P. falciparum malaria, plasma lactate levels on admission were related to the severity of the infection. Results from 12 of 61 patients fulfilled the criteria of severe malaria. RESULTS: Logistic regression analysis showed that a plasma lactate level above the upper range of normal was associated with an odds ratio of 31 (95% CI 6-164) for severe malaria. As a continuous variable, a 1 mmol/L increase in plasma lactate level was associated with an odds ratio of 12 (95% CI 3-50) for severe malaria. The sensitivity of an increased plasma lactate level on admission for severe malaria was 67% with a specificity of 94%. CONCLUSIONS: A timely determination of plasma lactate on admission may be helpful in the assessment of disease severity in travelers with imported P. falciparum malaria. An increased plasma lactate level should raise suspicion of a severe P. falciparum malaria infection, in particular when concomitant infections are not considered likely.

The value of C-reactive protein in cardiovascular risk prediction: the Rotterdam Study.

BACKGROUND: Epidemiologic studies have shown that C-reactive protein (CRP) is a risk factor for coronary heart disease. Whether routine measurement of CRP has a role in the prediction of future coronary disease in everyday clinical practice has not yet been investigated. METHODS: Within the Rotterdam Study, a population-based cohort study of 7983 men and women 55 years and older, we conducted a nested case-control study to investigate the value of CRP in coronary disease prediction. Data are based on 157 participants who experienced a myocardial infarction during follow-up and 500 randomly selected controls. High-sensitivity CRP and traditional cardiovascular risk factors were measured at baseline. RESULTS: The age- and sex-adjusted relative risk of myocardial infarction for subjects in the highest quartile of the population distribution of CRP compared with the lowest quartile was 2.0 (95% confidence interval, 1.1-3.4). After additional adjustment for traditional cardiovascular risk factors, the increase in risk largely disappeared (odds ratio, 1.2; 95% confidence interval, 0.6-2.2). Adding CRP to a coronary disease risk function based on risk factors that are routinely assessed in clinical practice or to the Framingham risk function did not improve the area under the receiver operating characteristic curve of these risk functions. Sensitivity and specificity of both risk functions, computed after dichotomizing the estimated disease probabilities using prespecified cutoff points, hardly improved when CRP was added. CONCLUSION: Measurement of CRP in elderly people has no additional value in coronary disease risk prediction when traditional cardiovascular risk factors are known.

Risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree: the Rotterdam Study.

BACKGROUND AND PURPOSE: Studies investigating determinants of atherosclerotic disease progression are relatively rare. Moreover, although atherosclerotic disease can be assessed noninvasively in different vascular beds, previous studies have not considered progression of atherosclerosis at >1 site. The present study was designed to identify risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree. METHODS: The Rotterdam Study is a population-based cohort study of 7983 men and women > or =55 years of age. Carotid plaques and intima-media thickness were assessed by ultrasound, aortic atherosclerosis by x-ray, and lower-extremity atherosclerosis by the ankle-arm index. Data on progression of atherosclerosis over an average period of 6.5 years were available for 3409 participants. Associations of established cardiovascular risk factors with mild, moderate, and severe progression of atherosclerosis were investigated through multinomial regression analysis. RESULTS: Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension were strong, independent predictors of moderate and severe progression of atherosclerosis at multiple sites. Diabetes mellitus predicted only severe progression of atherosclerosis. Associations of sex with progression of atherosclerosis were remarkably modest. CONCLUSIONS: Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension strongly predict progression of extracoronary atherosclerosis in the elderly, but sex remarkably does not. These results emphasize the need for prevention of progression of extracoronary atherosclerotic disease in men and women alike.

C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam Study.

UNLABELLED: Background and Purpose- C-reactive protein (CRP) predicts myocardial infarction and stroke. Its role as a predictor of the progression of subclinical atherosclerosis is not yet known. We investigated whether CRP predicts progression of atherosclerosis measured at various sites in the arterial tree. METHODS: CRP levels were measured in a random sample of 773 subjects >/=55 years of age who were participating in the Rotterdam Study. Subclinical atherosclerosis was assessed at various sites at 2 points in time, with a mean duration between measurements of 6.5 years. RESULTS: After adjustment for age, sex, and smoking habits, odds ratios (ORs) associated with CRP levels in the highest compared with the lowest quartile were increased for progression of carotid (OR, 1.9; 95% CI, 1.1 to 3.3), aortic (OR, 1.7; 95% CI, 1.0 to 3.0), iliac (OR, 2.0; 95% CI, 1.2 to 3.3), and lower extremity (OR, 1.9; 95% CI, 1.0 to 3.7) atherosclerosis. The OR for generalized progression of atherosclerosis as indicated by a composite progression score was 4.5 (95% CI, 2.3 to 8.5). Except for aortic atherosclerosis, these estimates hardly changed after additional adjustment for multiple cardiovascular risk factors. In addition, ORs for progression of atherosclerosis associated with high CRP levels were as high as those associated with the traditional cardiovascular risk factors high cholesterol, hypertension, and smoking. Geometric mean levels of CRP increased with the total number of sites showing progression of atherosclerosis (P=0.002 for trend). CONCLUSIONS: CRP predicts progression of atherosclerosis measured at various sites in the arterial tree.

C-reactive protein and arterial stiffness in older adults: the Rotterdam Study.

Arterial stiffness is one of the characteristics of vascular aging. Increases in pulse pressure, which reflect an increase in the stiffness of the large arteries, are associated with elevated C-reactive protein (CRP) levels. This may suggest a role of inflammation in the development of arterial stiffness. We investigated the relation between measures of arterial stiffness and CRP within the framework of the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. The carotid-femoral pulse wave velocity and the distensibility coefficient of the carotid artery were used as measures of arterial stiffness. Data on both arterial stiffness and CRP were available for 866 participants. In adjusted models, levels of CRP were linearly associated with pulse wave velocity (regression coefficient 0.088, 95% CI 0.006-0.170). Adjusted mean values of pulse wave velocity were significantly different across tertiles of CRP, being higher in the highest tertile of CRP. However, no significant association between CRP and carotid distensibility was observed.

Genetic variation in Fcgamma receptor IIa protects against advanced peripheral atherosclerosis. The Rotterdam Study.

Immune processes play a substantial role in atherosclerotic disease. The role in atherosclerosis of Fcgamma receptor IIa (FcgammaRIIa), a receptor for immunoglobulin G and for the inflammatory mediator C-reactive protein, is not yet clear. Since the R/H131 polymorphism in the FcgammaRIIa gene strongly influences binding to FcgammaRIIa, we investigated the association of the R/H131 polymorphism with advanced peripheral atherosclerosis. Within the Rotterdam Study, a population-based cohort study, we determined FcgammaRIIa genotype in 430 subjects with advanced peripheral atherosclerosis as indicated by the ankle-arm index, and 411 controls. Heterozygous and homozygous carriers of the H131 allele were protected against advanced peripheral atherosclerosis (age- and gender-adjusted odds ratio (OR) 0.77 (0.54-1.12) and 0.65 (0.44-0.98), respectively, P trend=0.04). This effect was most pronounced in subjects with modestly elevated levels of inflammation as indicated by the leukocyte count (OR 0.52 (0.29-0.93) and 0.45 (0.23-0.86), for heterozygotes and H131 homozygotes, respectively; P trend=0.02). This is the first study showing that the H131 allele of FcgammaRIIa protects against advanced peripheral atherosclerosis.