Association of Ideal Cardiovascular Metrics and Serum High-Sensitivity C-Reactive Protein in Hypertensive Population

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of cardiovascular disease. However, ideal cardiovascular health indicates lower risk of cardiovascular disease. This study aimed to investigate the effect of ideal cardiovascular health behaviors and health factors on hs-CRP levels among a hypertensive population. From 2006 to 2007, a cross-sectional study was conducted to survey 41,476 hypertensive subjects among the employees of Kailuan Corporation. Data from unified questionnaires and blood biochemical examinations were collected. The effects of ideal cardiovascular health behaviors and health factors on hs-CRP levels were evaluated through multivariate logistic regression analysis. A negative correlation was observed between hs-CRP levels and the number of ideal cardiovascular health metrics. The mean hs-CRP levels of subjects with zero to one, two, three, and four to six ideal cardiovascular health metrics were 1.11, 0.96, 0.90, and 0.80 mg/L, respectively (P<0.01). Multivariate logistic regression analysis revealed that after adjustment for sex, age, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other risk factors, the risks for subjects with two, three, and four to six ideal health metrics with serum hs-CRP >3 mg/L were lower than those with zero to one ideal health metrics, with corresponding odd ratios of 0.86 (95%CI: 0.79–0.93, P<0.01), 0.76 (95%CI: 0.69–0.83, P<0.01), and 0.68 (95%CI: 0.64–0.75, P<0.01), respectively. This finding suggests that ideal cardiovascular health behaviors and health factors were related to decreased hs-CRP levels in a hypertensive population.

Clinical Trial Registration

Unique identifier: ChiCTR-TNC-11001489.     

Gene-Specific DNA Methylation Association with Serum Levels of C-Reactive Protein in African Americans

A more thorough understanding of the differences in DNA methylation (DNAm) profiles in populations may hold promise for identifying molecular mechanisms through which genetic and environmental factors jointly contribute to human diseases. Inflammation is a key molecular mechanism underlying several chronic diseases including cardiovascular disease, and it affects DNAm profile on both global and locus-specific levels. To understand the impact of inflammation on the DNAm of the human genome, we investigated DNAm profiles of peripheral blood leukocytes from 966 African American participants in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. By testing the association of DNAm sites on CpG islands of over 14,000 genes with C-reactive protein (CRP), an inflammatory biomarker of cardiovascular disease, we identified 257 DNAm sites in 240 genes significantly associated with serum levels of CRP adjusted for age, sex, body mass index and smoking status, and corrected for multiple testing. Of the significantly associated DNAm sites, 80.5% were hypomethylated with higher CRP levels. The most significant Gene Ontology terms enriched in the genes associated with the CRP levels were immune system process, immune response, defense response, response to stimulus, and response to stress, which are all linked to the functions of leukocytes. While the CRP-associated DNAm may be cell-type specific, understanding the DNAm association with CRP in peripheral blood leukocytes of multi-ethnic populations can assist in unveiling the molecular mechanism of how the process of inflammation affects the risks of developing common disease through epigenetic modifications.     

Genetic Variants in C-Reactive Protein and Ischemic Stroke Susceptibility

Considerable discrepancies in the previously reported associations of the C-reactive protein (CRP) gene variants and ischemic stroke (IS) risk prompted us to perform this meta-analysis. We selected the fixed effects Mantel–Haenszel method to estimate the risk of IS [OR (odds ratio) along with its 95 % CI (confidence interval)] in relation to the CRP variants (?717 A > G, 1444 C > T). Heterogeneity test, influence analysis and publication bias test were appropriately performed using respective methods. We analyzed 1,926 IS patients and 2,678 controls and found the ?717 A > G variant was not significantly associated with overall IS risk. Subsequent analysis of the 1444 C > T variant involving 3,278 samples similarly revealed no significant association with IS. There was no substantial heterogeneity or publication bias in this analysis. Our meta-analysis may provide first evidence showing that genetic variants within the CRP locus are unlikely to modulate risk of IS.     

Associations of C-Reactive Protein,Granulocytes and Granulocyte-to-Lymphocyte Ratio with Mortality from Breast Cancer in Non-Institutionalized American Women

Inflammation may play a role in breast cancer, but evidence in the general population is lacking. We investigated the association between serum inflammatory markers (C-reactive protein (CRP), absolute granulocyte count (AGC) and granulocyte-to-lymphocyte (G/L) ratio) and breast cancer (BCa) mortality in American women while accounting for adiposity. From the Third National Health and Nutrition Examination Survey (NHANES III) we selected all women aged 20+ without any known history of cancer (n = 7,780). Multivariable Cox regression models were used to assess CRP, AGC and G/L ratio in relation to mortality from BCa, all cancer, cardiovascular disease and all causes. Stratification analyses by body mass index (BMI) and waist circumference were performed to investigate the effect of adiposity on this association. During a mean follow-up of 167 months, 44 women died from BCa. After adjustments for BMI and waist circumference, only G/L ratio was associated to risk of BCa death (e.g. HR: 2.35, 95% CI: 1.36–4.06 for the 3^rd compared to the 1^st tertile, P_trend = 0.01). Except for a borderline interaction between CRP categories and obesity by BMI, no statistically significant interaction between markers and categories of BMI or waist circumference was observed. All three markers were associated with mortality from cardiovascular disease and all causes. Our findings support a role of inflammation in BCa mortality which may involve mechanisms apart from obesity, and potential usefulness of GLR as a marker in assessing inflammation and cancer.     

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

Background

The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease.

Methods

This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped.

Results

A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother''s age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97–2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00–6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16–3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16–1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants.

Conclusion

The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE.     

Paradoxical Association of C-Reactive Protein with Endothelial Function in Rheumatoid Arthritis

Background

Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA).

Methodology/Principal Findings

Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P<0.01).

Conclusions/Significance

These findings argue against a causal role of CRP in atherogenesis and are consistent with a protective effect of CRP on EDNO bioavailability.     

A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation

Background

The acute-phase increase in serum C-reactive protein (CRP) is used to diagnose and monitor infectious and inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with chronic inflammation.

Methods and Findings

We studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. Erythrocyte sedimentation rate (ESR) was incorporated as an independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients. Common genetic variants at the CRP locus were associated with acute-phase serum CRP (for the most associated haplotype: p = 0.002, p<0.0005, p<0.0005 in patient sets 1, 2, and the combined sets, respectively), translating into an approximately 3.5-fold change in expected serum CRP concentrations between carriers of two common CRP haplotypes. For example, when ESR = 50 mm/h the expected geometric mean CRP (95% confidence interval) concentration was 43.1 mg/l (32.1–50.0) for haplotype 1 and 14.2 mg/l (9.5–23.2) for haplotype 4.

Conclusions

Our findings raise questions about the interpretation of acute-phase serum CRP. In particular, failure to take into account the potential for genetic effects may result in the inappropriate reassurance or suboptimal treatment of patients simply because they carry low-CRP–associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events: our findings impact on the use of these algorithms. For example, where access to effective, but expensive, biological therapies in rheumatoid arthritis is rationed on the basis of a DAS28-CRP clinical activity score, then two patients with identical underlying disease severity could be given, or denied, treatment on the basis of CRP genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement. Please see later in the article for the Editors'' Summary     

Maternal Serum C-Reactive Protein in Women with Preterm Prelabor Rupture of Membranes

Objective

This study evaluated maternal C-reactive protein (CRP) as a predictor of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes (PPROM) before and after 32 weeks of gestation.

Methods

This study was a prospective observational cohort study of 386 women. Maternal serum CRP concentrations were evaluated, and amniotic fluid samples were obtained via transabdominal amniocentesis at the time of admission. Placentas underwent histopathological examination after delivery. MIAC was defined based on a positive PCR for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive 16S rRNA gene amplification. HCA was defined based on the Salafia classification.

Results

Maternal CRP was significantly higher in women with MIAC and HCA (median 9.0 mg/l) than in women with HCA alone (median 6.9 mg/l), MIAC alone (median 7.4 mg/l) and without MIAC or HCA (median 4.5 mg/l) (p<0.0001). CRP was a weak predictor of the occurrence of MIAC and HCA before and after 32 weeks of gestation. Only the 95^th percentile of CRP and PPROM before 32 weeks exhibited a false-positive rate of 1%, a positive predictive value of 90% and a positive likelihood ratio of 13.2 to predict MIAC and HCA. However, the low sensitivity of 15% limits the clinical utility of this detection.

Conclusion

CRP is a poor predictor of the occurrence of MIAC and HCA, even at early gestational ages.     

Distinguishing type 2 diabetes from type 1 diabetes in African American and Hispanic American pediatric patients

Objective

To test the hypothesis that clinical observations made at patient presentation can distinguish type 2 diabetes (T2D) from type 1 diabetes (T1D) in pediatric patients aged 2 to 18.

Subjects and Methods

Medical records of 227 African American and 112 Hispanic American pediatric patients diagnosed as T1D or T2D were examined to compare parameters in the two diseases. Age at presentation, BMI z-score, and gender were the variables used in logistic regression analysis to create models for T2D prediction.

Results

The regression-based model created from African American data had a sensitivity of 92% and a specificity of 89%; testing of a replication cohort showed 91% sensitivity and 93% specificity. A model based on the Hispanic American data showed 92% sensitivity and 90% specificity. Similarities between African American and Hispanic American patients include: (1) age at onset for both T1D and T2D decreased from the 1980s to the 2000s; (2) risk of T2D increased markedly with obesity. Racial/ethnic-specific observations included: (1) in African American patients, the proportion of females was significantly higher than that of males for T2D compared to T1D (p<0.0001); (2) in Hispanic Americans, the level of glycated hemoglobin (HbA1c) was significantly higher in T1D than in T2D (p<0.002) at presentation; (3) the strongest contributor to T2D risk was female gender in African Americans, while the strongest contributor to T2D risk was BMI z-score in Hispanic Americans.

Conclusions

Distinction of T2D from T1D at patient presentation was possible with good sensitivity and specificity using only three easily-assessed variables: age, gender, and BMI z-score. In African American pediatric diabetes patients, gender was the strongest predictor of T2D, while in Hispanic patients, BMI z-score was the strongest predictor. This suggests that race/ethnic specific models may be useful to optimize distinction of T1D from T2D at presentation.     

Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations

Population linkage disequilibrium occurs as a consequence of mutation, selection, genetic drift, and population substructure produced by admixture of genetically distinct ethnic populations. African American and Hispanic ethnic groups have a history of significant gene flow among parent groups, which can be of value in affecting genome scans for disease-gene discovery in the case-control and transmission/disequilibrium test designs. Disease-gene discovery using mapping by admixture linkage disequilibrium (MALD) requires a map of polymorphic markers that differentiate between the founding populations, along with differences in disease-gene allele frequencies. We describe markers appropriate for MALD mapping by assessing allele frequencies of 744 short tandem repeats (STRs) in African Americans, Hispanics, European Americans, and Asians, by choosing STR markers that have large differences in composite delta, log-likelihood ratios, and/or I*(2) for MALD. Additional markers can be added to this MALD map by utilization of the rapidly growing single-nucleotide-polymorphism databases and the literature, to achieve a 3-10-cM scanning scale. The map will be useful for studies of diseases, including prostate and breast cancer, diabetes, hypertension, and end-stage renal disease, that have large differences in incidence between the founding populations of either Hispanics or African Americans.     

Resting Energy Expenditure in Obese African American and Caucasian Women

The prevalence of obesity among African American women approaches 50% and greatly exceeds rates for Caucasian women. In addition, black women lose less weight than white during obesity treatment and gain more weight when untreated. This study assessed resting energy expenditure (REE) and body composition in obese white (n=122) and black (n=44) women to explore the relationship between biological variables and these observed differences. REE and body composition were assessed by indirect calorimetry and densitometry, respectively, before weight loss. REE was significantly lower in black subjects (1637.6 ± 236.9 kcal/d) than in white (1731.4 ± 262.0) (p=0.04). REE remained significantly lower in blacks than whites after adjusting for body weight (p=0.02). REE, adjusted for fat-free mass, was also significantly lower in blacks than whites (p<0.0001), although the overestimation of fat-free mass by densitometry in blacks may have contributed to this finding. There were no differences between the groups in respiratory quotient. These results suggest that a decreased REE may exist in obese black women, and it may be related to the observed differences between black and white women in the prevalence of obesity and in the response to weight loss treatment. These crosssectional findings await confirmation in longitudinal studies.     

Pleiotropy among Common Genetic Loci Identified for Cardiometabolic Disorders and C-Reactive Protein

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10^-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.     

The Body Mass Index-Mortality Relationship in White and African American Women

Objective : To examine the association of body mass index to all-cause and cardiovascular disease (CVD) mortality in white and African American women. Research methods and procedures : Women who were members of the American Cancer Society Prevention Study I were examined in 1959 to 1960 and then followed 12 years for vital status. Data for this analysis were from 8,142 black and 100,000 white women. Body mass index (BMI) was calculated from reported height and weight. Associations were examined using Cox proportional hazards modeling with some analyses stratified by smoking (current or never) and educational status (less than complete high school or high school graduate). Results : There was a significant interaction between ethnicity and BMI for both all-cause (p<0.05) and CVD mortality (p<<0.001). BMI (as a continuous variable) was associated with all-dause mortality in white women in all four groups defined by smoking and education. In black women with less than a high school education, there were no significant associations between BMI mortality. For high school-educated black women, there was a significant association between BMI and all-cause mortality. Among never smoking women with at least a high school education, models using the lowest BMI as the reference indicated a 40% higher risk of all-cause mortality at a BMI of 35.9 in black women vs. 27.3 in white women. Discussion : The impact of BMI on mortality was modified by educational level in black women; however, BMI was a less potent risk factor in black women than in white women in the same category of educational status.     

Selectivity in Genetic Association with Sub-classified Migraine in Women

Migraine can be sub-classified not only according to presence of migraine aura (MA) or absence of migraine aura (MO), but also by additional features accompanying migraine attacks, e.g. photophobia, phonophobia, nausea, etc. all of which are formally recognized by the International Classification of Headache Disorders. It remains unclear how aura status and the other migraine features may be related to underlying migraine pathophysiology. Recent genome-wide association studies (GWAS) have identified 12 independent loci at which single nucleotide polymorphisms (SNPs) are associated with migraine. Using a likelihood framework, we explored the selective association of these SNPs with migraine, sub-classified according to aura status and the other features in a large population-based cohort of women including 3,003 active migraineurs and 18,108 free of migraine. Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 (LRP1) for MO. The number of loci associated with migraine increased to 11 at suggestive significance thresholds, including five additional selective associations for MO but none for MA. No two SNPs showed similar patterns of selective association with migraine characteristics. At one extreme, SNPs rs6790925 (near TGFBR2) and rs2274316 (MEF2D) were not associated with migraine overall, MA, or MO but were selective for migraine sub-classified by the presence of one or more of the additional migraine features. In contrast, SNP rs7577262 (TRPM8) was associated with migraine overall and showed little or no selectivity for any of the migraine characteristics. The results emphasize the multivalent nature of migraine pathophysiology and suggest that a complete understanding of the genetic influence on migraine may benefit from analyses that stratify migraine according to both aura status and the additional diagnostic features used for clinical characterization of migraine.     

Low C-Reactive Protein Levels in a Traditional West-African Population Living in a Malaria Endemic Area

Background

C-reactive protein (CRP) levels are reported to be elevated in populations of African descent living in affluent environments compared to populations of European ancestry. However, the natural history of CRP levels in populations of African descent living under adverse environments remains largely unknown.

Methods

CRP levels were measured with a high sensitivity assay in 624 apparently healthy individuals who contributed blood as part of a study on innate immune responsiveness in a traditional Ghanaian population living under adverse environmental conditions in a malaria endemic area. As a comparison, we included CRP measurements from 2931 apparently healthy individuals from the Dutch population that were included in the same batch of CRP analyses. Associations between CRP and body mass index (BMI), immune responsiveness, and P. falciparum parasitaemia were investigated.

Results

In an age- and sex-adjusted model, CRP levels were 0.54 mg/L lower in the Ghanaian compared to the Dutch cohort (1.52 vs. 0.98 mg/L, p<0.001). When accounting for the substantially higher average BMI in the Dutch compared to the Ghanaians (25.6 vs. 18.4 kg/m²) the difference in CRP levels disappeared. BMI associated positively with CRP in the Dutch but not in the Ghanaians. In individuals with an acute phase response, CRP levels were higher in the Ghanaian compared to the Dutch cohort (24.6 vs. 17.3 mg/L, p = 0.04). Levels of CRP were positively related to immune responsiveness and P. falciparum parasitaemia (all p<0.001) among Ghanaians.

Conclusions

Our study demonstrates that West-Africans do not exhibit an inherently high inflammatory state. The role of genes, environment and gene-environment interaction in explaining reports of elevated CRP levels in populations of African ancestry when compared to other ethnicities living in affluent environments thus merits further investigation.     

Genetic Analysis of Hispanic Individuals with Cystic Fibrosis

We have performed molecular genetic analyses of Hispanic individuals with cystic fibrosis (CF) in the southwestern United States. Of 129 CF chromosomes analyzed, only 46% (59/129) carry ΔF508. The G542X mutation was found on 5% (7/129) of CF chromosomes. The 3849+10kbC→T mutation, detected primarily in Ashkenazi Jews, was present on 2% (3/129). R1162X and R334W, mutations identified in Spain and Italy, each occurred on 1.6% (2/129) of CF chromosomes. W1282X and R553X were each detected once. G551D and N1303K were not found. Overall, screening for 22 or more mutations resulted in detection of only 58% of CF transmembrane conductance regulator gene mutations among Hispanic individuals. Analysis of KM19/XV2c haplotypes revealed an unusual distribution. Although the majority of ΔF508 mutations are on chromosomes of B haplotypes, the other CF mutations are on A and C haplotypes at higher-than-expected frequencies. These genetic analyses demonstrate significant differences between Hispanic individuals with CF and those of the general North American population. Assessment of carrier/affected risk in Hispanic CF individuals cannot, therefore, be based on the mutation frequencies found through studies of the general population but must be adjusted to better reflect the genetic makeup of this ethnic group. Further studies are necessary to identify the causative mutation(s) in this population and to better delineate genotype/phenotype correlations. These will enable counselors to provide more accurate genetic counseling.     

NT-proBNP,C-Reactive Protein and Soluble uPAR in a Bi-Ethnic Male Population: The SAfrEIC Study

Objective and design

This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort.

Methods and subjects

We measured NT-proBNP, C-reactive protein (CRP) and plasma-soluble urokinase plasminogen activator receptor (suPAR) levels along with conventional biomarkers in black (n = 117) and white (n = 116) men.

Results

NT-proBNP, CRP and suPAR levels were higher in black compared to white men. NT-proBNP was significantly associated with both CRP (r = 0.38; p = 0.001) and suPAR (r = 0.42; p<0.001) in black men only. After full adjustment in multiple regression analyses, the above associations of NT-proBNP with CRP (β = 0.199; p = 0.018) and suPAR (β = 0.257; p<0.01) were confirmed in black men.

Conclusion

These results suggest that a low-grade inflammatory state as reflected by both a conventional and novel marker of inflammation may contribute to higher cardiovascular risk as reflected by the associations obtained with a marker of cardiac strain in black South African men.