C-reactive protein, established risk factors and social inequalities in cardiovascular disease – the significance of absolute versus relative measures of disease

<p>Abstract</p> <p>Background</p> <p>The widespread use of relative scales in socioepidemiological studies has recently been criticized. The criticism is based mainly on the fact that the importance of different risk factors in explaining social inequalities in cardiovascular disease (CVD) varies, depending on which scale is used to measure social inequalities. The present study examines the importance of established risk factors, as opposed to low-grade inflammation, in explaining socioeconomic differences in the incidence of CVD, using both relative and absolute scales.</p> <p>Methods</p> <p>We obtained information on socioeconomic position (SEP), established risk factors (smoking, hypertension, and hyperlipidemia), and low-grade inflammation as measured by high-sensitive (hs) C-reactive protein (CRP) levels, in 4,268 Swedish men and women who participated in the Malmö Diet and Cancer Study (MDCS). Data on first cardiovascular events, i.e., stroke or coronary event (CE), was collected from regional and national registers. Social inequalities were measured in relative terms, i.e., as ratios between incidence rates in groups with lower and higher SEP, and also in absolute terms, i.e., as the absolute difference in incidence rates in groups with lower and higher SEP.</p> <p>Results</p> <p>Those with low SEP had a higher risk of future CVD. Adjustment for risk factors resulted in a rather small reduction in the relative socioeconomic gradient, namely 8% for CRP (≥ 3 mg/L) and 21% for established risk factors taken together. However, there was a reduction of 18% in the absolute socioeconomic gradient when looking at subjects with CRP-levels < 3 mg/L, and of 69% when looking at a low-risk population with no smoking, hypertension, or hyperlipidemia.</p> <p>Conclusion</p> <p>C-reactive protein and established risk factors all contribute to socioeconomic differences in CVD. However, conclusions on the importance of "modern" risk factors (here, CRP), as opposed to established risk factors, in the association between SEP and CVD depend on the scale on which social inequalities are measured. The one-sided use of the relative scale, without including a background of absolute levels of disease, and of what causes disease, can consequently prevent efforts to reduce established risk factors by giving priority to research and preventive programs looking in new directions.</p

Prevalence and Prognostic Significance of Asymptomatic Peripheral Arterial Disease in 68-year-old Men with Diabetes. Results from the Population Study 'Men Born in 1914' from Malmo, Sweden.

AbstractObjectiveTo assess the prevalence of asymptomatic peripheral arterial disease (PAD) in older men with diabetes and to compare the incidence of cardiac events and deaths in diabetic and non-diabetic men with abnormal and normal systolic ankle–brachial pressure index, respectively.Research design and methodsPopulation-based cohort of 68-year-old men (n=474). Diabetes was defined as history of diabetes or a fasting blood glucose ≥6.1mmol/l. PAD was defined as an ankle–brachial pressure index (ABI) <0.9 in either leg. Fourteen-year mortality and cardiac event rates were based on record linkage with regional and national registers.ResultsThe prevalence of PAD in men with and without diabetes was 29 and 12%, respectively (p=0.003). The incidence of cardiac events was 22.9/1000 person years in men free from both diabetes and PAD. In the absence of an abnormal pressure index, diabetes was associated with an event rate of 28.4 (p=0.469). In the presence of an abnormal index the incidence was 102 (p<0.001). This pattern remained in the multivariate analysis when other atherosclerotic risk factors were taken into account. Cardiovascular mortality rates similarly differed substantially between diabetic men with and without PAD.ConclusionsA fasting blood glucose value above 6.1mmol/l even in the absence of symptoms indicating diabetes was associated by an increased prevalence of asymptomatic PAD. The cardiovascular risk in diabetes varied widely between men with and without abnormal ankle–brachial pressure index

Multiple anthropometric measures in relation to incidence of diabetes: a Swedish population-based cohort study.

Obesity is the major modifiable risk factor for diabetes. This study investigated the incidence of diabetes in relation to multiple anthropometric measures

Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death.

AIMS: To compare the incidence of myocardial infarction and death in non-diabetic subjects with and without insulin resistance. METHODS: Population-based prospective cohort study, in Malmö, Sweden, of 4748 non-diabetic subjects (60% women), aged 46-68 years, with no history of myocardial infarction or stroke. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the sex-specific 75th percentile (1.80 for women and 2.12 for men). Incidence of myocardial infarction and death is based on record linkage with local and national registers. Cox's proportional hazards model was used to assess the influence of insulin resistance after adjustment for age, sex, hyperglycaemia, raised arterial blood pressure, dyslipidaemia, central obesity, smoking and leisure-time physical activity. RESULTS: Sixty-two subjects suffered a coronary event, and 93 subjects died during the 6-year follow-up period. Insulin resistance was after adjustment for other factors included in the insulin resistance syndrome and other potential confounders, associated with an increased incidence of coronary events (relative risk (RR) 2.18; 95% confidence interval (CI) 1.22-3.87; P = 0.008) and deaths (RR 1.62; 1.03-2.55; P = 0.038). CONCLUSIONS: Insulin resistance, as assessed by the HOMA method, was in this cohort of middle-aged non-diabetic subjects associated with an increased incidence of myocardial infarction and death. This risk remained when smoking, low physical activity and factors included in the insulin resistance syndrome were taken into account in a stepwise regression model. Diabet. Med. 19, 470-475 (2002

Development of a diet quality index assessing adherence to the Swedish nutrition recommendations and dietary guidelines in the Malmö Diet and Cancer cohort.

OBJECTIVE: To develop a diet quality index (DQI) that assesses adherence to the Swedish nutrition recommendations (SNR) and the Swedish dietary guidelines (SDG). DESIGN: A cross-sectional study within the Malmö Diet and Cancer (MDC) cohort. A diet history method collected dietary data, a structured questionnaire lifestyle and socio-economic information, and anthropometric data were collected by direct measurements. The index (DQI-SNR) included six components: SFA, PUFA, fish and shellfish, dietary fibre, fruit and vegetables, and sucrose. SETTING: Malmö, Sweden. SUBJECTS: Men (n 4525) and women (n 8491) of the MDC cohort enrolled from September 1994 to October 1996. RESULTS: For participants with high DQI-SNR scores, nutrient and food intakes were close to recommendations. However, most of the study population exceeded the recommended intake for SFA (98 %) and few reached recommended intakes for dietary fibre (24 %), fruit and vegetables (32 %), vitamin D (18 %) and folate (2 %). A high DQI-SNR score was positively associated with age, physical activity, not smoking, past food habit change, education and socio-economic status. Individuals with high scores were more likely to have a diabetes diagnosis or experienced a cardiovascular event. CONCLUSIONS: Results suggest that the DQI-SNR is a useful tool for assessing adherence to the SNR 2005 and the SDG in the MDC cohort. No index has previously been developed with the aim of evaluating adherence to the current dietary recommendations in Sweden. Further validation of the DQI-SNR, and evaluation of its utility, is needed

Acute-phase proteins and incidence of diabetes: a population-based cohort study

Aims: To examine the relationship between plasma levels of the acute-phase proteins ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin and C-reactive protein (CRP), and incidence of diabetes in the population-based Malmö Diet and Cancer Study—Cardiovascular Cohort (MDCS-CC). Methods: The study population consists of 4246 participants (aged 46–67 years, 60.8 % women) with no previous history of diabetes. Participants were followed, and incidence of diabetes was assessed by linkage with national registers and a clinical re-examination of the cohort. Cox proportional hazard regression analysis was used to compare incidence of diabetes in relation to sex-specific quartiles of the acute-phase proteins. Results: During a mean follow-up period of 15.6 ± 3.4 years, a total of 390 participants were diagnosed with diabetes. Orosomucoid, haptoglobin, and CRP showed a significant increased risk of diabetes after adjustment for potential confounders. However, further adjustments for fasting glucose at baseline resulted in significant association only for CRP. The multivariable-adjusted hazard ratios (HR: 4th vs. 1st quartile) were 1.18 (95 % CI: 0.83–1.67; p = 0.51), 1.19 (CI: 0.85–1.62; p = 0.10), and 1.40 (CI: 1.01–1.95; p = 0.046) for orosomucoid, haptoglobin, and CRP respectively. Conclusion: The study demonstrated that there are associations between orosomucoid, haptoglobin and CRP and the risk of incidence of diabetes. However, after additional adjustment for fasting glucose levels at baseline, the association stayed significant only for CRP

Plasma S100A8/A9 Correlates With Blood Neutrophil Counts, Traditional Risk Factors, and Cardiovascular Disease in Middle-Aged Healthy Individuals.

The S100 alarmins A8, A9, and A8/A9, secreted by activated neutrophils and monocytes/macrophages, are involved in the pathogenesis of various inflammatory diseases. S100A8/A9 has previously been linked to atherogenesis and cardiovascular (CV) disease. We investigated whether S100A8, A9, and A8/A9 correlate with carotid artery disease and CV risk in apparently healthy individuals

Hypertension and Genetic Variation in Endothelial-Specific Genes

Genome-wide association (GWA) studies usually detect common genetic variants with low-to-medium effect sizes. Many contributing variants are not revealed, since they fail to reach significance after strong correction for multiple comparisons. The WTCCC study for hypertension, for example, failed to identify genome-wide significant associations. We hypothesized that genetic variation in genes expressed specifically in the endothelium may be important for hypertension development. Results from the WTCCC study were combined with previously published gene expression data from mice to specifically investigate SNPs located within endothelial-specific genes, bypassing the requirement for genome-wide significance. Six SNPs from the WTCCC study were selected for independent replication in 5205 hypertensive patients and 5320 population-based controls, and successively in a cohort of 16537 individuals. A common variant (rs10860812) in the DRAM (damage-regulated autophagy modulator) locus showed association with hypertension (P = 0.008) in the replication study. The minor allele (A) had a protective effect (OR = 0.93; 95% CI 0.88-0.98 per A-allele), which replicates the association in the WTCCC GWA study. However, a second follow-up, in the larger cohort, failed to reveal an association with blood pressure. We further tested the endothelial-specific genes for co-localization with a panel of newly discovered SNPs from large meta-GWAS on hypertension or blood pressure. There was no significant overlap between those genes and hypertension or blood pressure loci. The result does not support the hypothesis that genetic variation in genes expressed in endothelium plays an important role for hypertension development. Moreover, the discordant association of rs10860812 with blood pressure in the case control study versus the larger Malmo "Preventive Project-study highlights the importance of rigorous replication in multiple large independent studies