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1.  Comparing Self-reported Disease Outcomes, Diet, and Lifestyles in a National Cohort of Black and White Seventh-day Adventists 
Preventing Chronic Disease  2007;4(3):A62.
Few epidemiologic cohort studies on the etiology of chronic disease are powerful enough to distinguish racial and ethnic determinants from socioeconomic determinants of health behaviors and observed disease patterns. The Adventist Health Study-2 (AHS-2), with its large number of respondents and the variation in lifestyles of its target populations, promises to shed light on these issues. This paper focuses on some preliminary baseline analyses of responses from the first group of participants recruited for AHS-2.
We administered a validated and pilot-tested questionnaire on various lifestyle practices and health outcomes to 56,754 respondents to AHS-2, comprising 14,376 non-Hispanic blacks and 42,378 non-Hispanic whites. We analyzed cross-sectional baseline data adjusted for age and sex and performed logistic regressions to test differences between responses from the two racial groups.
In this Seventh-day Adventist (Adventist) cohort, blacks were less likely than whites to be lifelong vegetarians and more likely to be overweight or obese. Exercise levels were lower for blacks than for whites, but blacks were as likely as whites not to currently smoke or drink. Blacks reported higher rates of hypertension and diabetes than did whites but lower rates of high serum cholesterol, myocardial infarction, emphysema, and all cancers. After we eliminated skin cancer from the analysis, the age-adjusted prevalence of cancer remained significantly lower for black than for white women. The prevalence of prostate cancer was 47% higher for black men than for white men.
The profile of health habits for black Adventists is better than that for blacks nationally. Given the intractable nature of many other contributors to health disparities, including racism, housing segregation, employment discrimination, limited educational opportunity, and poorer health care, the relative advantage for blacks of the Adventist lifestyle may hold promise for helping to close the gap in health status between blacks and whites nationally.
PMCID: PMC1955428  PMID: 17572966
2.  Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study) 
PLoS Medicine  2010;7(4):e1000263.
Peter Whincup and colleagues carry out a cross-sectional study examining ethnic differences in precursors of of type 2 diabetes among children aged 9–10 living in three UK cities.
Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood.
Methods and Findings
We performed a cross-sectional survey of 4,796 children aged 9–10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference −2.9, 95% CI −4.5 to −1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased.
Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Worldwide, nearly 250 million people have diabetes, and the number of people affected by this chronic disease is increasing rapidly. Diabetes is characterized by dangerous amounts of sugar (glucose) in the blood. Blood sugar levels are normally controlled by insulin, a hormone that the pancreas releases when blood sugar levels rise after eating (digestion of food produces glucose). In people with type 2 diabetes (the most common type of diabetes), blood sugar control fails because the fat and muscle cells that usually respond to insulin by removing sugar from the blood become less responsive to insulin (insulin resistant). Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. Long-term complications of diabetes include kidney failure, blindness, nerve damage, and an increased risk of developing cardiovascular problems, including heart disease and stroke.
Why Was This Study Done?
South Asians and African-Caribbeans living in Western countries tend to have higher rates of type 2 diabetes than host populations. South Asian adults living in the UK, for example, have a 3-fold higher risk of developing type 2 diabetes than white Europeans. They also have higher fasting blood levels of glucose, insulin and triglycerides (a type of fat), higher blood levels of “glycated hemoglobin” (HbA1c; an indicator of average of blood-sugar levels over time), more body fat (increased adiposity), raised levels of a molecule called C-reactive protein, and lower levels of HDL-cholesterol (another type of fat) than white Europeans. Most of these “diabetes precursors” (risk factors) are also seen in black African-Caribbean adults living in the UK except that individuals in this ethnic group often have raised HDL-cholesterol levels and low triglyceride levels. Ethnic differences in type 2 diabetes precursors are also present in adolescents, but the extent to which they are present in childhood remains unclear. Knowing this information could have implications for diabetes prevention. In this population-based study, therefore, the researchers investigate patterns of diabetes precursors in 9- to 10-year-old UK children of white European, South Asian, and black African-Caribbean origin.
What Did the Researchers Do and Find?
The researchers enrolled nearly 5,000 children (including 1,153 white European, 1,306 South Asian and 1,215 black African-Caribbean children) from primary schools with high prevalences of ethnic minority pupils in London, Birmingham, and Leicester in the Child Heart and Health study in England (CHASE). They measured and weighed more than two-thirds of the enrolled children and determined their adiposity. They also took blood samples for measurement of diabetes precursors from nearly two-thirds of the children. The recorded ethnicity of each child was based on parental definition. The researchers' analysis of these data showed that, compared with white Europeans, South Asian children had higher levels of HbA1c, insulin, triglycerides, and C-reactive protein but lower HDL-cholesterol levels. In addition, they had higher adiposity levels than the white European children, but this did not account for the observed differences in the other diabetes precursors. Black African-Caribbean children also had higher levels of HbA1c, insulin, and C-reactive protein than white European children, although the differences were smaller than those between South Asians and white Europeans. Similar to black African-Caribbean adults, however, children of this ethnic origin had higher HDL-cholesterol and lower triglyceride levels than white Europeans.
What Do These Findings Mean?
These findings indicate that ethnic differences in diabetes precursors are already present in apparently healthy children before they are 10 years old. Furthermore, most of the ethnic differences in diabetes precursors seen among the children follow the pattern seen in adults. Although these findings need confirming in more children, they suggest that the ethnic differences in type 2 diabetes susceptibility first described in immigrants to the UK are persisting in UK-born South Asian and black African-Caribbean children. Most importantly, these findings suggest that some of the factors thought to be responsible for ethnic differences in type 2 diabetes—for example, varying levels of physical activity and dietary differences—are operating well before adult life. Interventions that target these factors early could, therefore, offer good opportunities for diabetes prevention in high-risk ethnic groups, provided such interventions are carefully tailored to the needs of these groups.
Additional Information
Please access these Web sites via the online version of this summary at
The International Diabetes Federation provides information about all aspects of diabetes (in English, French and Spanish)
The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health-care professionals and the general public, including information on diabetes in specific US populations (in English and Spanish)
The UK National Health Service also provides information for patients and carers about type 2 diabetes (in several languages)
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
The US Agency for Healthcare Research and Quality has a fact sheet on diabetes disparities among racial and ethnic minorities
PMCID: PMC2857652  PMID: 20421924
3.  Type of Vegetarian Diet, Body Weight, and Prevalence of Type 2 Diabetes 
Diabetes Care  2009;32(5):791-796.
We assessed the prevalence of type 2 diabetes in people following different types of vegetarian diets compared with that in nonvegetarians.
The study population comprised 22,434 men and 38,469 women who participated in the Adventist Health Study-2 conducted in 2002–2006. We collected self-reported demographic, anthropometric, medical history, and lifestyle data from Seventh-Day Adventist church members across North America. The type of vegetarian diet was categorized based on a food-frequency questionnaire. We calculated odds ratios (ORs) and 95% CIs using multivariate-adjusted logistic regression.
Mean BMI was lowest in vegans (23.6 kg/m2) and incrementally higher in lacto-ovo vegetarians (25.7 kg/m2), pesco-vegetarians (26.3 kg/m2), semi-vegetarians (27.3 kg/m2), and nonvegetarians (28.8 kg/m2). Prevalence of type 2 diabetes increased from 2.9% in vegans to 7.6% in nonvegetarians; the prevalence was intermediate in participants consuming lacto-ovo (3.2%), pesco (4.8%), or semi-vegetarian (6.1%) diets. After adjustment for age, sex, ethnicity, education, income, physical activity, television watching, sleep habits, alcohol use, and BMI, vegans (OR 0.51 [95% CI 0.40–0.66]), lacto-ovo vegetarians (0.54 [0.49–0.60]), pesco-vegetarians (0.70 [0.61–0.80]), and semi-vegetarians (0.76 [0.65–0.90]) had a lower risk of type 2 diabetes than nonvegetarians.
The 5-unit BMI difference between vegans and nonvegetarians indicates a substantial potential of vegetarianism to protect against obesity. Increased conformity to vegetarian diets protected against risk of type 2 diabetes after lifestyle characteristics and BMI were taken into account. Pesco- and semi-vegetarian diets afforded intermediate protection.
PMCID: PMC2671114  PMID: 19351712
4.  Plasma Cytokine Levels in a Population-Based Study: Relation to Age and Ethnicity 
Aging is one factor believed to contribute to processes that underlie chronic low-grade inflammation in older adults. Moreover, more recent studies have suggested that cytokine levels are influenced by ethnicity.
In this study, we determined plasma cytokine profiles in a population-based sample (n = 1,411; aged 25–91 years) to determine the relationship between circulating cytokine levels, aging, and ethnicity. We measured interleukin-1 receptor antagonist (IL-1ra), interleukin (IL)-6, -10, C-reactive protein (CRP), and tumor necrosis factor-receptor 1 (TNF-r1).
IL-6 and TNF-r1 significantly increased with age, whereas IL-1ra, IL-10, and CRP did not significantly increase with age. After adjusting for age, non-Hispanic whites had significantly higher levels of IL-1ra than Mexican Americans, whereas non-Hispanic blacks had significantly higher levels of IL-6 and CRP than Mexican Americans as well as non-Hispanic whites. CRP levels in non-Hispanic blacks were no longer significantly higher after adjusting for body mass index (BMI), indicating that BMI is an important predictor of this inflammatory marker.
These results demonstrate that cytokine levels are influenced by both age and ethnicity. Furthermore, these results show that inflammatory profiles for Mexican Americans are lower than non-Hispanic whites and non-Hispanic blacks.
PMCID: PMC2844059  PMID: 20018825
IL-6; IL-10; IL-1; TNF; CRP
5.  Vegetarian diets and incidence of diabetes in the Adventist Health Study-2 
To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2.
Methods and Results
Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses.
Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.
PMCID: PMC3638849  PMID: 21983060
Vegetarianism; Black; African American; Diabetes; Ethnicity; Diet
6.  Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2) 
Public health nutrition  2012;15(10):1909-1916.
Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores.
Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns.
Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire.
Five hundred white subjects representing the AHS-2 cohort.
Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI.
We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.
PMCID: PMC3443300  PMID: 22230619
Vegetarian diet; Blood pressure
7.  Taiwanese Female Vegetarians Have Lower Lipoprotein-Associated Phospholipase A2 Compared with Omnivores 
Yonsei Medical Journal  2010;52(1):13-19.
Many studies supported that vegetarians have a lower risk of cardiac diseases and mortality, partly due to better blood pressure and serum cholesterol profiles. However, the inflammatory markers, especially lipoprotein-associated phospholipase A2 (Lp-PLA2), have not been well-studied. This study aimed to compare inflammatory markers and conventional risk factors between vegetarians and omnivores.
Materials and Methods
One hundred and seventy-three vegetarians and 190 omnivores were studied. Fasting blood samples were obtained to compare levels of glucose, total cholesterol, triacylglycerol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, homocysteine, Lp-PLA2 activity, and high-sensitivity C-reactive protein (hs-CRP).
Vegetarians had higher serum levels of the following markers: hs-CRP (1.8 ± 3.4 vs. 1.2 1.8 mg/L, respectively; p = 0.05), homocysteine (9.39 ± 3.22 vs. 7.62 ± 2.41 µmol/L, respectively; p < 0.01), and triacylglycerol (96.91 ± 59.56 vs. 84.66 ± 43.24 mg/dL, respectively; p < 0.05). Vegetarians also had lower levels of Lp-PLA2 (18.32 ± 7.19 10-3 µmol/min/mL vs. 20.22 8.13 10-3 µmol/min/mL; p < 0.05), total cholesterol (180.62 ± 36.55 mg/dL vs. 192.73 ± 36.57 mg/dL; p < 0.01), LDL cholesterol (118.15 ± 32.8 vs. 126.41 ± 34.28 mg/dL; p < 0.05), and HDL cholesterol (55.59 ± 13.30 vs. 62.09 ± 14.52 mg/dL, p < 0.01). Multivariate analyses demonstrated that a vegetarian diet increases the chances for high serum hs-CRP and low Lp-PLA2 activity.
In addition to lower total cholesterol, LDL-cholesterol, and HDL-cholesterol, Taiwanese female vegetarians have lower serum Lp-PLA2 activity but higher levels of hs-CRP, homocysteine, and triacylglyerol. It might be due to geographic differences of vegetarian diets, and further studies are needed.
PMCID: PMC3017687  PMID: 21155029
Vegetarian diet; risk factors; lipoprotein associated phospholipase A2; C-reactive protein; inflammation
8.  Inflammation, Insulin Resistance, and Diabetes—Mendelian Randomization Using CRP Haplotypes Points Upstream 
PLoS Medicine  2008;5(8):e155.
Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.
Methods and Findings
We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29–1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52–0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007–0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25–0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations.
Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP.
Using a Mendelian randomization approach, Eric Brunner and colleagues show that the associations between serum C-reactive protein and insulin resistance, glycemia, and diabetes are likely to be noncausal.
Editors' Summary
Diabetes—a common, long-term (chronic) disease that causes heart, kidney, nerve, and eye problems and shortens life expectancy—is characterized by high levels of sugar (glucose) in the blood. In people without diabetes, blood sugar levels are controlled by the hormone insulin. Insulin is released by the pancreas after eating and “instructs” insulin-responsive muscle and fat cells to take up the glucose from the bloodstream that is produced by the digestion of food. In the early stages of type 2 diabetes (the commonest type of diabetes), the muscle and fat cells become nonresponsive to insulin (a condition called insulin resistance), and blood sugar levels increase. The pancreas responds by making more insulin—people with insulin resistance have high blood levels of both insulin and glucose. Eventually, however, the insulin-producing cells in the pancreas start to malfunction, insulin secretion decreases, and frank diabetes develops.
Why Was This Study Done?
Globally, about 200 million people have diabetes, but experts believe this number will double by 2030. Ways to prevent or delay the onset of diabetes are, therefore, urgently needed. One major risk factor for insulin resistance and diabetes is being overweight. According to one theory, increased body fat causes mild, chronic tissue inflammation, which leads to insulin resistance. Consistent with this idea, people with higher than normal amounts of the inflammatory protein C-reactive protein (CRP) in their blood have a high risk of developing diabetes. If inflammation does cause diabetes, then drugs that inhibit CRP might prevent diabetes. However, simply measuring CRP and determining whether the people with high levels develop diabetes cannot prove that CRP causes diabetes. Those people with high blood levels of CRP might have other unknown factors in common (confounding factors) that are the real causes of diabetes. In this study, the researchers use “Mendelian randomization” to examine whether increased blood CRP causes diabetes. Some variants of CRP (the gene that encodes CRP) increase the amount of CRP in the blood. Because these variants are inherited randomly, there is no likelihood of confounding factors, and an association between these variants and the development of insulin resistance and diabetes indicates, therefore, that increased CRP levels cause diabetes.
What Did the Researchers Do and Find?
The researchers measured blood CRP levels in more than 5,000 people enrolled in the Whitehall II study, which is investigating factors that affect disease development. They also used the “homeostasis model assessment-insulin resistance” (HOMA-IR) method to estimate insulin sensitivity from blood glucose and insulin measurements, and measured levels of hemoglobin A1c (HbA1c, hemoglobin with sugar attached—a measure of long-term blood sugar control) in these people. Finally, they looked at three “single polynucleotide polymorphisms” (SNPs, single nucleotide changes in a gene's DNA sequence; combinations of SNPs that are inherited as a block are called haplotypes) in CRP in each study participant. Common haplotypes of CRP were related to blood serum CRP levels and, as previously reported, increased blood CRP levels were associated with diabetes and with HOMA-IR and HbA1c values indicative of insulin resistance and poor blood sugar control, respectively. By contrast, CRP haplotypes were not related to HOMA-IR or HbA1c values. Similarly, pooled analysis of CRP haplotypes and diabetes in Whitehall II and another large study on health determinants (the Northwick Park Heart Study II) showed no association between CRP variants and diabetes risk. Finally, data from the Wellcome Trust Case Control Consortium also showed no association between CRP haplotypes and diabetes risk.
What Do These Findings Mean?
Together, these findings suggest that increased blood CRP levels are not responsible for the development of insulin resistance or diabetes, at least in European populations. It may be that there is a causal relationship between CRP levels and diabetes risk in other ethnic populations—further Mendelian randomization studies are needed to discover whether this is the case. For now, though, these findings suggest that drugs targeted against CRP are unlikely to prevent or delay the onset of diabetes. However, they do not discount the possibility that proteins involved earlier in the inflammatory process might cause diabetes and might thus represent good drug targets for diabetes prevention.
Additional Information.
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Bernard Keavney
The MedlinePlus encyclopedia provides information about diabetes and about C-reactive protein (in English and Spanish)
US National Institute of Diabetes and Digestive and Kidney Diseases provides patient information on all aspects of diabetes, including information on insulin resistance (in English and Spanish)
The International Diabetes Federation provides information about diabetes, including information on the global diabetes epidemic
The US Centers for Disease Control and Prevention provides information for the public and professionals on all aspects of diabetes (in English and Spanish)
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC2504484  PMID: 18700811
9.  Socioeconomic position, health behaviors, and C-reactive protein: A moderated-mediation analysis 
We sought to understand the link between low SEP and cardiovascular disease (CVD) by examining the association between SEP, health-related coping behaviors, and C-reactive protein (CRP), an inflammatory marker and independent risk factor for CVD in a US sample of adults.
We used a multiple mediation model to evaluate how these behaviors work in concert to influence CRP levels and whether these relationships were moderated by gender and race/ethnicity.
Main outcome measures
CRP levels were divided into two categories: elevated CRP (3.1–10.0 mg/L) and normal CRP (≤ 3.0 mg/L).
Both poverty and low educational attainment were associated with elevated CRP, and these associations were primarily explained through higher levels of smoking and lower levels of exercise. In the education model, poor diet also emerged as a significant mediator. These behaviors accounted for 87.9% of the total effect of education on CRP and 55.8% the total effect of poverty on CRP. We also found significant moderation of these mediated effects by gender and race/ethnicity.
These findings demonstrate the influence of socioeconomically-patterned environmental constraints on individual-level health behaviors. Specifically, reducing socioeconomic inequalities may have positive effects on CVD disparities through reducing cigarette smoking and increasing vigorous exercise.
PMCID: PMC2881158  PMID: 20496985
C-reactive protein; mediation; moderation; socioeconomic position; health behaviors
10.  Vegetarian diets and cardiovascular risk factors in black members of the Adventist Health Study-2 
Public health nutrition  2014;18(3):537-545.
To compare cardiovascular risk factors between vegetarians and non-vegetarians in black individuals living in the USA.
A cross-sectional analysis of a sub-set of 592 black women and men enrolled in the Adventist Health Study-2 (AHS-2) cohort of Seventh-day Adventists.
Members of the AHS-2 cohort, who lived in all states of the USA and provinces of Canada.
Black/African-American members of two sub-studies of AHS-2 where blood and physiological measurements were obtained.
Of these women and men, 25% were either vegan or lacto-ovo-vegetarians (labelled ‘vegetarian/vegans’), 13 % were pesco-vegetarian and 62% were non-vegetarian. Compared with non-vegetarians, the vegetarian/vegans had odds ratios for hypertension, diabetes, high blood total cholesterol and high blood LDL-cholesterol of 0·56 (95% CI 0·36, 0·87), 0·48 (95% CI 0·24, 0·98), 0·42 (95% CI 0·27, 0·65) and 0·54 (95% CI 0·33, 0·89), respectively, when adjusted for age, gender, education, physical activity and sub-study. Corresponding odds ratios for obesity in vegetarian/vegans and pesco-vegetarians, compared with non-vegetarians, were 0·43 (95% CI 0·28, 0·67) and 0·47 (95% CI 0·27, 0·81), respectively; and for abdominal obesity 0·54 (95% CI 0·36, 0·82) and 0·50 (95% CI 0·29, 0·84), respectively. Results for pesco-vegetarians did not differ significantly from those of non-vegetarians for other variables. Further adjustment for BMI suggested that BMI acts as an intermediary variable between diet and both hypertension and diabetes.
As with non-blacks, these results suggest that there are sizeable advantages to a vegetarian diet in black individuals also, although a cross-sectional analysis cannot conclusively establish cause.
PMCID: PMC4167463  PMID: 24636393
Vegetarian diet; Cardiovascular risks; Blacks; Adventists
11.  Racial/Ethnic and Gender Differences in the Association between Self-Reported Experiences of Racial/Ethnic Discrimination and Inflammation in the CARDIA Cohort of 4 US Communities 
Social science & medicine (1982)  2012;75(5):922-931.
Inflammation is etiologically implicated in cardiometabolic diseases for which there are known racial/ethnic disparities. Prior studies suggest there may be an association between self-reported experiences of racial/ethnic discrimination and inflammation, particularly C-reactive protein (CRP). It is not known whether that association is influenced by race/ethnicity and gender. In separate hierarchical linear models with time-varying covariates we examined that association among 901 Black women, 614 Black men, 958 White women, and 863 White men in the Coronary Artery Risk Development in Young Adults (CARDIA) study of young adults in four US communities. Self-reported experiences of racial/ethnic discrimination were ascertained in 1992–93 and 2000–01. Inflammation was measured as log-transformed CRP in those years and 2005–06. All analyses were adjusted for blood pressure, plasma total cholesterol, triglycerides, homeostatic model assessment for insulin resistance (HOMA-IR), age, education, and community. Our findings extend prior research by suggesting that, broadly speaking, self-reported experiences of racial/ethnic discrimination are associated with inflammation; however, this association is complex and varies for Black and White women and men. Black women reporting 1 or 2 experiences of discrimination had higher levels of CRP compared to Black women reporting no experiences of discrimination (β = 0.141, SE = 0.062, P < 0.05). This association was not statistically significant among Black women reporting 3 or more experiences of discrimination and not independent of modifiable risks (smoking and obesity) in the final model. White women reporting 3 or more experiences of discrimination had significantly higher levels of CRP compared to White women reporting no experiences of discrimination independent of modifiable risks in the final model (β = 0.300, SE = 0.113, P < 0.01). The association between self-reported experiences of racial/ethnic discrimination and CRP was not statistically significant among Black and White men reporting 1 or 2 experiences of discrimination. Further research is needed.
PMCID: PMC3417223  PMID: 22682683
USA; Racial/ethnic discrimination; Blacks; Whites; Inflammation; C-reactive protein; Hierarchical linear models; gender
12.  High Vegetable Fats Intake Is Associated with High Resting Energy Expenditure in Vegetarians 
Nutrients  2015;7(7):5933-5947.
It has been demonstrated that a vegetarian diet may be effective in reducing body weight, however, the underlying mechanisms are not entirely clear. We investigated whether there is a difference in resting energy expenditure between 26 vegetarians and 26 non-vegetarians and the correlation between some nutritional factors and inflammatory markers with resting energy expenditure. In this cross-sectional study, vegetarians and non-vegetarians were matched by age, body mass index and gender. All underwent instrumental examinations to assess the difference in body composition, nutrient intake and resting energy expenditure. Biochemical analyses and 12 different cytokines and growth factors were measured as an index of inflammatory state. A higher resting energy expenditure was found in vegetarians than in non-vegetarians (p = 0.008). Furthermore, a higher energy from diet, fibre, vegetable fats intake and interleukin-β (IL-1β) was found between the groups. In the univariate and multivariable analysis, resting energy expenditure was associated with vegetarian diet, free-fat mass and vegetable fats (p < 0.001; Slope in statistic (B) = 4.8; β = 0.42). After adjustment for cytokines, log10 interleukin-10 (IL-10) still correlated with resting energy expenditure (p = 0.02). Resting energy expenditure was positively correlated with a specific component of the vegetarian’s diet, i.e., vegetable fats. Furthermore, we showed that IL-10 was positively associated with resting energy expenditure in this population.
PMCID: PMC4517036  PMID: 26193314
vegetarians; plant rich diet; energy expenditure; obesity
13.  Racial and Ethnic Differences in Mortality of Hemodialysis Patients: Role of Dietary and Nutritional Status and Inflammation 
American Journal of Nephrology  2011;33(2):157-167.
Racial/ethnic disparities prevail among hemodialysis patients. We hypothesized that significant differences exist between Black and non-Hispanic and Hispanic White hemodialysis patients in nutritional status, dietary intake and inflammation, and that they account for racial survival disparities.
In a 6-year (2001–2007) cohort of 799 hemodialysis patients, we compared diet and surrogates of nutritional-inflammatory status and their mortality-predictabilities between 279 Blacks and 520 Whites using matched and regression analyses and Cox with cubic splines.
In age-, gender- and diabetes-matched analyses, Blacks had higher lean body mass and serum prealbumin, creatinine and homocysteine levels than Whites. In case-mix-adjusted analyses, dietary intakes in Blacks versus Whites were higher in energy (+293 ± 119 cal/day) and fat (+18 ± 5 g/day), but lower in fiber (−2.9 ± 1.3 g/day) than Whites. In both races, higher serum albumin, prealbumin and creatinine were associated with greater survival, whereas CRP and IL-6, but not TNF-α, were associated with increased mortality. The highest (vs. lowest) quartile of IL-6 was associated with a 2.4-fold (95% CI: 1.3–3.8) and 4.1-fold (2.2–7.2) higher death risk in Blacks and Whites, respectively.
Significant racial disparities exist in dietary, nutritional and inflammatory measures, which may contribute to hemodialysis outcome disparities. Testing race-specific dietary and/or anti-inflammatory interventions is indicated.
PMCID: PMC3202917  PMID: 21293117
Black race; Hispanic ethnicity; African Americans; Non-Hispanic White; Nutritional status; Inflammatory markers; Dietary intake; Survival
14.  Relationship of carotid intima-media thickness and duration of vegetarian diet in Chinese male vegetarians 
Many studies have shown that vegetarian diet has beneficial effects on the prevention of cardiovascular diseases. However, the effect of vegetarian diet on carotid intima-media thickness (IMT), as well as the association between IMT and duration of vegetarian diet, are still unclear. The present study aims to investigate the influence of duration of vegetarian diet on cardiovascular risk factors, and more importantly on IMT among Chinese vegetarians.
One hundred and seventy-one Chinese male vegetarians were screened for metabolic profile, cardiovascular risk and carotid IMT. They were compared with 129 age-matched omnivores recruited from a community-based health project. The effects of confounding factors were adjusted by stepwise logistic regression analysis.
Compared to the omnivores, the vegetarians had lower BMI, weight, systolic blood pressure and diastolic blood pressure. Also, the levels of triglyceride, total cholesterol, HDL-Cholesterol, LDL-Cholesterol, ApoA1, ApoB, uric acid, albumin and γ-glutamyltransferase were significantly reduced in vegetarians. Omnivores had significantly higher fasting blood glucose than that of vegetarians. However, there were no differences in fasting insulin, C-reactive protein and HOMA-IR between the two groups. IMT was thinner in the vegetarian group than in the omnivore group (0.59 ± 0.16 vs. 0.63 ± 0.10 cm, P < 0.05). The vegetarians were divided according to duration of vegetarian diet (< 6 years, 6 to ≤ 11 years, > 11 years), those in tertile 1 (< 6 years) and tertile 2 (6 to ≤ 11 years) had shown thinner IMT as compared to the omnivores, and tertile 3 had shown no reduction.
A decrease in multiple cardiovascular risk factors such as BMI, blood pressure and lipid profile was associated with vegetarian diet. Moreover, taking a low-calorie, low-protein, or vegetarian diet might have great beneficial effects on IMT through improved lipid profile, and the beneficial effects appeared to be correlated with the duration of vegetarian diet.
PMCID: PMC3184257  PMID: 21929760
vegetarian diet; IMT; duration of vegetarian diet
15.  “Association of Socioeconomic Status with Inflammation Markers in Black and White Men and Women in the Coronary Artery Risk Development in Young Adults (CARDIA) Study” 
Social science & medicine (1982)  2009;69(3):451-459.
Inflammatory processes are implicated in a number of diseases for which there are known socioeconomic status (SES) disparities, including heart disease and diabetes. Growing evidence also suggests SES gradients in levels of peripheral blood markers of inflammation. However, we know little about potential gender and racial/ethnic differences in associations between SES and inflammation, despite the fact that the burden of inflammation-related diseases varies by gender and race. The present study examines SES (education and income) gradients in levels of two inflammatory biomarkers, C-reactive protein (CRP) and interleukin-6 (IL-6), in a biethnic (White and Black) sample of men and women (n = 3,549, aged 37-55 years) in the USA from the CARDIA Study. Health status, behavioral and psychosocial variables that may underlie SES differences in inflammatory biomarker levels were also examined. Age-adjusted CRP and IL-6 levels were inversely associated with education level in each race/gender group except Black males. Income gradients were also observed in each race/gender group for IL-6 and in White females and males for CRP. In general, differences in CRP and IL-6 levels between low and high SES groups were reduced in magnitude and significance with the addition of health status, behavioral, and psychosocial variables, although the impact of the addition of model covariates varied across race/gender groups and different SES-inflammation models. Overall, findings indicate SES gradients in levels of inflammation burden in middle-aged White and Black males and females.
PMCID: PMC2747365  PMID: 19524346
USA; inflammation; C-reactive protein; interleukin-6; socioeconomic status (SES); gender; race/ethnicity; biomarkers; health inequalities
16.  Explorations into the Synergy Between Faith, Health, and Health-Care Among Black Baptists 
U.S. health disparities are documented by race/ethnic, socioeconomic, gender, and geographic demographics. Since federal health record keeping began, regardless of other demographic factors, Black people continue to record statistical significant disparities. The complementary and alternative medicine (CAM) domain of mind-body medicine provides a method and language to assess the metaphysical constructs of faith, spirituality and religion and their influence on health and healthcare practices. Explorations into the synergy between faith, health and healthcare among a convenient sample of Black Baptist conventioneers provides an opportunity to better understand if and how faith can be used to enhance the health and wellbeing of Black people.
In 2005 a convenience sample of 2,500 Black persons among 10,000 Joint Baptist conventioneers participated in the study; 1,827 completed and returned an 80 item questionnaire. 500 surveys were lost due to computer malfunctions. Survey results covered: demographic, health/safety, health care, and faith/religion/health.
58.6% of respondents were women; 61% were married. Most (66.2%) reported good health and few were told by their physician they had a chronic disease. 33.5% never talk to their pastor about health problems or (42.7%) physician visits. Mental health responses: (98.7%) get along well with others; (93.6%) were satisfied with life; (92.8%) feel good about themselves; and (97.6%) were in good spirits most times. Many were in social organizations (40.6%). 96.1% felt religion was very important in their life; 91% thought religion affects physical/mental health; and 89.1% believed faith affects mental/physical health. 95.7% believe faith can change a health crisis. Most described religion and faith differently.
The Black Church has history in social justice connected to community health. Responses to religion/faith affirm the interconnectedness of the synergy between faith-health. Empowered by religious fervor to interpret their health status as positive; they must also balance perceptions with evidence-based health decision-making, health practices, and sustained healthcare utilization.
A thoughtful scrutiny of the constructs of health and healthcare enable a new paradigm – Optimal Health – to emerge2 The Black Church has and must forever be the institution that helps Black people to continue to grow and develop in journeying to reach their best possible emotional, intellectual, physical, spiritual, and socioeconomic greatest state of aliveness, which is Optimal Health.3 In order to maximize the synergy between faith, health and health care; individuals, groups, and communities must harmonize physical, social, psychological, and spiritual well-being.4 The spiritual component can serve as the foundation on which the other three components rest.5 Considering many in this study who attended church or religious services three (3) or more times within the past 30 days and they rarely talked to their pastor concerning health problems or what their physician told them; the religious/church service through sermons, Sunday school, Bible class and various ministries can serve as a platform for health promotion in the Black Church and the larger Black community.
PMCID: PMC4046858  PMID: 24910479
17.  Relationship of vitamin D levels to blood pressure in a biethnic population 
Background and aims
Accumulating epidemiological and clinical studies have sug gested that vitamin D insufficiency may be associated with hypertension. Blacks tend to have lower vitamin D levels than Whites, but it is unclear whether this difference explains the higher blood pressure (BP) observed in Blacks in a population with healthy lifestyle practices.
Methods and results
We examined cross-sectional data in the Adventist Health Study-2 (AHS-2), a cohort of non-smoking, mostly non-drinking men and women following a range of diets from vegan to non-vegetarian. Each participant provided dietary, demographic, lifestyle and medical history data. Measurements of weight, height, waist circumference, percent body fat and blood pressure and fasting blood samples were obtained from a randomly selected non-diabetic sample of 284 Blacks and 284 Whites aged 30–95 years. Multiple regression analyses were used to assess independent relationships between blood pressure and 25(OH)D levels. Levels of 25(OH)D were inversely associated with systolic BP in Whites after control for age, gender, BMI, and use of BP-lowering medications (β-coefficient −0.23 [95% CI, −0.43, −0.03; p = 0.02]). This relationship was not seen in Blacks (β-coefficient 0.08 [95% CI, −0.14, 0.30; p = 0.4]). Results were similar when controlling for waist circumference or percentage body fat instead of BMI. No relationship between serum 25(OH)D and diastolic BP was seen.
Systolic BP is inversely associated with 25(OH)D levels in Whites but not in Blacks. Vitamin D may not be a major contributor to the White-Black differential in BP.
PMCID: PMC3522760  PMID: 22770642
Serum hydroxyvitamin D; Blood pressure; Diet; Ethnic groups
18.  Everyday Discrimination Prospectively Predicts Inflammation Across 7-Years in Racially Diverse Midlife Women: Study of Women's Health Across the Nation 
The Journal of social issues  2014;70(2):298-314.
Self-reported discrimination has emerged as a predictor of negative psychological and physical health outcomes across racial/ethnic groups. The goals of this study were to determine whether C-reactive protein (CRP), a marker of inflammation and risk factor for future cardiovascular disease (CVD) was independently predicted by everyday discrimination or whether race or body mass index (BMI) modified this association over a 7-year period among 2,490 women from racially diverse backgrounds. At baseline, the 10-item Williams' measure of everyday discrimination was administered. Generalized estimating equations were used to assess these associations. Descriptive results showed that Black and Chinese women reported greater discrimination than White, Japanese, and Hispanic women, while Black and Hispanic women had the highest levels of CRP over the 7-year period. There was no main effect of everyday discrimination (B = .003, SE = .005, p = .58) and this association did not differ as a function of race (p's > .05). The everyday discrimination × BMI interaction term significantly predicted higher CRP levels over time in the full sample of women (p = .03). Specifically, in non-obese women (BMI less than 30), higher perceived everyday discrimination was associated with higher CRP levels over the 7-year period. These findings were independent of demographic, negative affect, biomedical, and behavioral factors. The results demonstrate that greater everyday discrimination is associated with increased inflammation over time in non-obese women. These findings highlight the implications of interpersonal sources of social stress for long-term physical health via their impact on intermediary biological pathways, specifically inflammation. Greater emphasis on such linkages is warranted as we work towards ameliorating health disparities exacerbated by individual-level factors.
PMCID: PMC4203661  PMID: 25342861
everyday discrimination; C-reactive protein; cardiovascular diseases; inflammation
19.  Beyond Meatless, the Health Effects of Vegan Diets: Findings from the Adventist Cohorts 
Nutrients  2014;6(6):2131-2147.
Vegetarians, those who avoid meat, and vegans, additionally avoiding dairy and eggs, represent 5% and 2%, respectively, of the US population. The aim of this review is to assess the effects of vegetarian diets, particularly strict vegetarian diets (i.e., vegans) on health and disease outcomes. We summarized available evidence from three prospective cohorts of Adventists in North America: Adventist Mortality Study, Adventist Health Study, and Adventist Health Study-2. Non-vegetarian diets were compared to vegetarian dietary patterns (i.e., vegan and lacto-ovo-vegetarian) on selected health outcomes. Vegetarian diets confer protection against cardiovascular diseases, cardiometabolic risk factors, some cancers and total mortality. Compared to lacto-ovo-vegetarian diets, vegan diets seem to offer additional protection for obesity, hypertension, type-2 diabetes, and cardiovascular mortality. Males experience greater health benefits than females. Limited prospective data is available on vegetarian diets and body weight change. Large randomized intervention trials on the effects of vegetarian diet patterns on neurological and cognitive functions, obesity, diabetes, and other cardiovascular outcomes are warranted to make meaningful recommendations.
PMCID: PMC4073139  PMID: 24871675
vegetarian; vegan; lacto-ovo-vegetarian; Adventist; Health; AMS; AHS; cardiovascular; cancer; mortality
20.  Socioeconomic and racial/ethnic differentials of C-reactive protein levels: a systematic review of population-based studies 
BMC Public Health  2007;7:212.
Socioeconomic and racial/ethnic factors strongly influence cardiovascular disease outcomes and risk factors. C-reactive protein (CRP), a non-specific marker of inflammation, is associated with cardiovascular risk, and knowledge about its distribution in the population may help direct preventive efforts. A systematic review was undertaken to critically assess CRP levels according to socioeconomic and racial/ethnic factors.
Medline was searched through December 2006 for population-based studies examining CRP levels among adults with respect to indicators of socioeconomic position (SEP) and/or race/ethnicity. Bibliographies from located studies were scanned and 26 experts in the field were contacted for unpublished work.
Thirty-two relevant articles were located. Cross-sectional (n = 20) and cohort studies (n = 11) were included, as was the control group of one trial. CRP levels were examined with respect to SEP and race/ethnicity in 25 and 15 analyses, respectively. Of 20 studies that were unadjusted or adjusted for demographic variables, 19 found inverse associations between CRP levels and SEP. Of 15 similar studies, 14 found differences between racial/ethnic groups such that whites had the lowest while blacks, Hispanics and South Asians had the highest CRP levels. Most studies also included adjustment for potential mediating variables in the causal chain between SEP or race/ethnicity and CRP. Most of these studies showed attenuated but still significant associations.
Increasing poverty and non-white race was associated with elevated CRP levels among adults. Most analyses in the literature are underestimating the true effects of racial/ethnic and socioeconomic factors due to adjustment for mediating factors.
PMCID: PMC2018719  PMID: 17705867
21.  The Effects of Ethnic Discrimination and Socioeconomic Status on Endothelin-1 Among Blacks and Whites 
American journal of hypertension  2009;22(7):698-704.
Ethnic disparities in cardiovascular disease (CVD) may partially reflect differences in chronic stress burden that vary by social class and exposure to ethnic discrimination. Stress is associated with increased endothelin-1 (ET-1). This study examined the relationship of ET-1 to socioeconomic status (SES) and to perceived ethnic discrimination among black (n = 51) and white (n = 65) adults (mean age 36.5).
The Perceived Discrimination subscale of the Scale of Ethnic Experience measured exposure to discrimination and the Hollingshead Two-Factor Index of Social Position assessed SES. Plasma ET-1 was sampled upon awakening after an overnight admission.
SES and ET-1 levels were similar across ethnic groups, but mean discrimination scores were higher among blacks than whites (P < 0.001). Multiple regressions found that the SES × ethnicity interaction was associated with ET-1 (P < 0.05), after adjustment for gender, resting mean arterial pressure (MAP), body mass index (BMI), and exercise frequency. Regressions stratified by ethnicity revealed that lower SES correlated with higher ET-1 in whites (P < 0.001), but not blacks, and accounted for 21% of the variance. Another series of regressions revealed an interaction effect of ethnicity by discrimination on ET-1 (P < 0.05). Increased discrimination correlated with increased ET-1 among blacks (P < 0.05), but not whites, and explained 11% of the variance after adjustment for SES, gender, exercise frequency, and socially desirable response bias.
Thus, ET-1 levels increased in association with different psychosocial burdens in blacks and whites. Plasma ET-1 was higher among whites with lower SES and among blacks with higher levels of perceived ethnic discrimination, regardless of SES.
PMCID: PMC2811580  PMID: 19390511
22.  Between-group differences in nutrition- and health- related psychosocial factors among US adults and their associations with diet, exercise, and weight status 
Large disparities exist across ethnic and socioeconomic status (SES) groups regarding obesity and other chronic diseases. Eliminating health disparities is a national priority in the US.
To test between-group differences in nutrition- and health-related psychosocial factors (NHRPF) and their associations with US adults’ diet, exercise, and weight status.
Design and participants/setting
Nationally representative data from the Continuing Survey of Food Intakes by Individuals and the Diet and Health Knowledge Survey in 1994-96 from 4,356 US adults aged 20-65 years were used. Diet was assessed using 24-hour recalls; NHRPF, by 25 questions; weight status, by self-reported weight and height. Index scores were created to measure NHRPF. Diet quality was assessed using the US Department of Agriculture 2005 Healthy Eating Index (HEI).
Statistical analyses
Multivariate linear and logistic regression models were conducted to examine the associations.
Some ethnic differences in NHRPF existed but were small. There were statistically significant (P<0.05) and large ethnic differences in diet (blacks had the worst average HEI; whites, the best, at 47.6 vs. 52.3, respectively). Groups with higher SES had better NHRPF (had better nutrition knowledge and beliefs, made better food choices, and had better awareness of nutrition-related health risks) and HEI. Subjects with high school education had higher NHRPF score (37.2 vs. 35.7) and HEI (54.5 vs. 49.5) than those with less than a high school education.
Ethnic differences among American adults’ NHRPF were small, but SES differences were greater. More efforts are needed to study the influences of the complex interactions between individual and social environmental factors that affect Americans’ diet and weight status and to explain related ethnic disparities.
PMCID: PMC3378980  PMID: 22709700
ethnicity; nutrition; psychosocial; dietary intake; weight status; disparity
23.  Diagnosis of the Metabolic Syndrome Is Associated With Disproportionately High Levels of High-Sensitivity C-Reactive Protein in Non–Hispanic Black Adolescents 
Diabetes Care  2011;34(3):734-740.
Whereas it is known that the metabolic syndrome (MetS) has a paradoxically lower prevalence in non–Hispanic black adolescents than in non–Hispanic whites or Hispanics, the relative severity of MetS by race/ethnicity is unknown. Inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), is a key factor linking MetS to cardiovascular disease and type 2 diabetes. Our goal was to determine whether elevations of hsCRP vary by race/ethnicity among adolescents with MetS.
We used the National Health and Nutrition Examination Survey (1999–2008) and evaluated adolescents (age 12–19 years) using a pediatric/adolescent adaptation of the ATP III definition of MetS. We used linear regression to evaluate the interaction between MetS status and ethnicity with respect to hsCRP concentration.
For male and female adolescents, MetS was associated with elevated hsCRP levels compared with adolescents without MetS. However, the elevation in hsCRP between adolescents with and without MetS was greater in non–Hispanic blacks compared with that in non–Hispanic whites (P = 0.04) but not that in Hispanics (P = 0.18). hsCRP concentrations correlated with individual MetS components similarly among all ethnicities. In an evaluation of adolescents diagnosed with MetS, non–Hispanic blacks had higher BMI and more hypertension than other ethnicities but there were no other racial/ethnic differences in the features of MetS.
Non–Hispanic black adolescents have a greater differential in hsCRP between those with and those without MetS than the differential in non–Hispanic whites but not that in Hispanics. Therefore, even though MetS has a low prevalence in non–Hispanic blacks, MetS is a particularly good indicator of inflammation in non–Hispanic black adolescents.
PMCID: PMC3041218  PMID: 21285387
24.  A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation 
PLoS Medicine  2010;7(9):e1000341.
A genetic association study by Timothy Vyse and colleagues suggests that there is a significant association between CRP variants and acute-phase serum CRP concentrations in patients with rheumatoid arthritis, including those with chronic inflammation.
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.
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
Editors' Summary
C-reactive protein (CRP) is a serum marker for inflammation or infection and acts by binding to a chemical (phosphocholine) found on the surface of dead or dying cells (and some types of bacteria) in order to activate the immune system (via the complement system). Fat cells release factors that stimulate the liver to produce CRP, and serum levels greater than 10 mg/l are generally considered indicative of an infectious or inflammatory process. After an inflammatory stimulus, serum CRP levels may exceed 500 times baseline, so CRP is used in all medical specialities to help diagnose inflammation and infection. Although patients with chronic inflammatory diseases, such as rheumatoid arthritis, have raised levels of CRP, levels of CRP are still highly variable. Some studies have suggested that there may be genetic variations of CRP (CRP variants) that determine the magnitude of the acute-phase CRP response, a finding that has important clinical implications: CRP thresholds are used as a diagnostic component of formal clinical algorithms and play an important role in a clinician's decision-making process when diagnosing inflammatory disease and choosing treatment options. Therefore, it is possible that false reassurance could be given to a patient with disease, or optimal treatment withheld, because some patients are genetically predisposed to have only a modest increase in acute-phase CRP.
Why Was This Study Done?
Although some studies have looked at the CRP gene variant response, few, if any, studies have examined the CRP gene variant response in the context of chronic inflammation, such as in rheumatoid arthritis. Therefore, this study aimed to determine whether CRP gene variants could also influence CRP serum levels in rheumatoid arthritis.
What Did the Researchers Do and Find?
The authors studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients): one patient set used a cohort of 281 patients in the UK, and the other patient set (used for replication) consisted of 414 patients from New Zealand and Australia. A genetic technique (a tagSNP approach) was used to capture common variations at the CRP locus (haplotype association analysis) at both the population and the individual level. The relationship between genotype and serum CRP was explored by linear modeling. The researchers found that common genetic variants at the CRP locus were associated with acute-phase serum CRP in both patient sets translating into an approximate 3.5-fold change in expected serum CRP between carriers of two common CRP variants. For example, when ESR = 50 mm/h the expected CRP serum level for one common CRP variant was 43.1 mg/l and for another CRP variant was 14.2 mg/l.
What Do These Findings Mean?
The findings of this study raise questions about the interpretation of acute-phase serum CRP, as they suggest that there is a significant association between CRP variants and acute-phase serum CRP concentrations in a group of patients with rheumatoid arthritis, including those with chronic active inflammation. The size of the genetic effect may be large enough to have a clinically relevant impact on the assessment of inflammatory disease activity, which in turn may influence therapeutic decision making. Failure to take into account the potential for genetic effects may result in the inappropriate reassurance or undertreatment 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, so these findings impact on the use of such algorithms. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement.
Additional Information
Please access these Web sites via the online version of this summary at
Lab Test Online provides information on CRP
The Wellcome Trust provides a glossary of genetic terms
Learn.Genetics provides access to the Genetic Science Learning Center, which is part of the human genome project
PMCID: PMC2943443  PMID: 20877716
25.  The Promise of Prevention: The Effects of Four Preventable Risk Factors on National Life Expectancy and Life Expectancy Disparities by Race and County in the United States 
PLoS Medicine  2010;7(3):e1000248.
Majid Ezzati and colleagues examine the contribution of a set of risk factors (smoking, high blood pressure, elevated blood glucose, and adiposity) to socioeconomic disparities in life expectancy in the US population.
There has been substantial research on psychosocial and health care determinants of health disparities in the United States (US) but less on the role of modifiable risk factors. We estimated the effects of smoking, high blood pressure, elevated blood glucose, and adiposity on national life expectancy and on disparities in life expectancy and disease-specific mortality among eight subgroups of the US population (the “Eight Americas”) defined on the basis of race and the location and socioeconomic characteristics of county of residence, in 2005.
Methods and Findings
We combined data from the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System to estimate unbiased risk factor levels for the Eight Americas. We used data from the National Center for Health Statistics to estimate age–sex–disease-specific number of deaths in 2005. We used systematic reviews and meta-analyses of epidemiologic studies to obtain risk factor effect sizes for disease-specific mortality. We used epidemiologic methods for multiple risk factors to estimate the effects of current exposure to these risk factors on death rates, and life table methods to estimate effects on life expectancy. Asians had the lowest mean body mass index, fasting plasma glucose, and smoking; whites had the lowest systolic blood pressure (SBP). SBP was highest in blacks, especially in the rural South—5–7 mmHg higher than whites. The other three risk factors were highest in Western Native Americans, Southern low-income rural blacks, and/or low-income whites in Appalachia and the Mississippi Valley. Nationally, these four risk factors reduced life expectancy at birth in 2005 by an estimated 4.9 y in men and 4.1 y in women. Life expectancy effects were smallest in Asians (M, 4.1 y; F, 3.6 y) and largest in Southern rural blacks (M, 6.7 y; F, 5.7 y). Standard deviation of life expectancies in the Eight Americas would decline by 0.50 y (18%) in men and 0.45 y (21%) in women if these risks had been reduced to optimal levels. Disparities in the probabilities of dying from cardiovascular diseases and diabetes at different ages would decline by 69%–80%; the corresponding reduction for probabilities of dying from cancers would be 29%–50%. Individually, smoking and high blood pressure had the largest effect on life expectancy disparities.
Disparities in smoking, blood pressure, blood glucose, and adiposity explain a significant proportion of disparities in mortality from cardiovascular diseases and cancers, and some of the life expectancy disparities in the US.
Please see later in the article for the Editors' Summary
Editors' Summary
Life expectancy (a measure of longevity and premature death) and overall health have increased steadily in the United States over recent years. New drugs, new medical technologies, and better disease prevention have all helped Americans to lead longer, healthier lives. However, even now, some Americans live much longer and much healthier lives than others. Health disparities—differences in how often certain diseases occur and cause death in groups of people classified according to their ethnicity, geographical location, sex, or age—are extremely large and persistent in the US. On average, black men and women in the US live 6.3 and 4.5 years less, respectively, than their white counterparts; the gap between life expectancy in the US counties with the lowest and highest life expectancies is 18.4 years for men and 14.3 years for women. Disparities in deaths (mortality) from chronic diseases such as cardiovascular diseases (for example, heart attacks and stroke), cancers, and diabetes are known to be the main determinants of these life expectancy disparities.
Why Was This Study Done?
Preventable risk factors such as smoking, high blood pressure, excessive body fat (adiposity), and high blood sugar are responsible for many thousands of deaths from chronic diseases. Exposure to these risk factors varies widely by race, state of residence, and socioeconomic status. However, the effects of these observed disparities in exposure to modifiable risk factors on US life expectancy disparities have only been examined in selected groups of people and it is not known how multiple modifiable risk factors affect US health disparities. A better knowledge about how disparities in risk factor exposure contribute to health disparities is needed to ensure that prevention programs not only improve the average health status but also reduce health disparities. In this study, the researchers estimate the effects of smoking, high blood pressure, high blood sugar, and adiposity on US life expectancy and on disparities in life expectancy and disease-specific deaths among the “Eight Americas,” population groups defined by race and by the location and socioeconomic characteristics of their county of residence.
What Did the Researchers Do and Find?
The researchers extracted data on exposure to these risk factors from US national health surveys, information on deaths from different diseases in 2005 from the US National Center for Health Statistics, and estimates of how much each risk factor increases the risk of death from each disease from published studies. They then used modeling methods to estimate the effects of risk factor exposure on death rates and life expectancy. The Asian subgroup had the lowest adiposity, blood sugar, and smoking rates, they report, and the three white subgroups had the lowest blood pressure. Blood pressure was highest in the three black subgroups, whereas the other three risk factors were highest in Western Native Americans, Southern rural blacks, and whites living in Appalachia and the Mississippi Valley. The effects on life expectancy of these factors were smallest in Asians and largest in Southern rural blacks but, overall, these risk factors reduced the life expectancy for men and women born in 2005 by 4.9 and 4.1 years, respectively. Other calculations indicate that if these four risk factors were reduced to optimal levels, disparities among the subgroups in deaths from cardiovascular diseases and diabetes and from cancers would be reduced by up to 80% and 50%, respectively.
What Do These Findings Mean?
These findings suggest that disparities in smoking, blood pressure, blood sugar, and adiposity among US racial and geographical subgroups explain a substantial proportion of the disparities in deaths from cardiovascular diseases, diabetes, and cancers among these subgroups. The disparities in risk factor exposure also explain some of the disparities in life expectancy. The remaining disparities in deaths and life expectancy could be the result of preventable risk factors not included in this study—one of its limitations is that it does not consider the effect of dietary fat, alcohol use, and dietary salt, which are major contributors to different diseases. Thus, suggest the researchers, reduced exposure to preventable risk factors through the implementation of relevant policies and programs should reduce life expectancy and mortality disparities in the US and yield health benefits at a national scale.
Additional Information
Please access these Web sites via the online version of this summary at
The US Centers for Disease Control and Prevention, the US Office of Minority Health, and the US National Center on Minority Health and Health Disparities all provide information on health disparities in the US
MedlinePlus provides links to information on health disparities and on healthy living (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of healthy living
The American Heart Association and the American Cancer Society provide information on modifiable risk factors for patients and caregivers
Healthy People 2010 is a national framework designed to improve the health of people living in the US
The US National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) collect information on risk factor exposures in the US
PMCID: PMC2843596  PMID: 20351772

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