Optimal serum cholesterol concentrations are associated with accelerated bone loss in African ancestry men.

UNLABELLED: We tested if serum lipid and lipoprotein cholesterol levels are associated with longitudinal measures of bone mineral density (BMD) in 1289 African ancestry men. After 6 years of mean follow-up, men with clinically optimal levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglycerides at baseline experienced the greatest BMD loss, independent of potential confounding factors (all p < 0.05). INTRODUCTION: Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change. METHODS: We determined the association of serum triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up, 6.1 years) measures of BMD in a cohort of 1289 in African ancestry men (mean age, 56.4 years). Fasting serum triglycerides, HDL, and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD, and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline, or high risk for triglyceride, HDL, and LDL concentrations based on Adult Treatment Panel III guidelines. RESULTS: Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p < 0.05). Similarly, men classified as having optimal levels of LDL, HDL, or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p < 0.05), independent of potential confounding factors. CONCLUSIONS: We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings.

Association of volumetric bone mineral density with abdominal aortic calcification in African ancestry men.

SUMMARY: We tested for association between cortical and trabecular volumetric bone mineral density (vBMD) with abdominal aortic calcification (AAC) prevalence in 278 Afro-Caribbean men. AAC was present in 68.3 % of the men. Greater cortical, but not trabecular, vBMD was associated with significantly decreased odds of AAC independent of traditional risk factors. INTRODUCTION: The aim of this study is to assess the prevalence and correlates of AAC in a sample of 278 Afro-Caribbean men (mean age 56) and to test for a largely unexplored association between cortical and trabecular vBMD with AAC prevalence. METHODS: Men were recruited consecutively as part of an ongoing prospective cohort study of body composition in men aged 40+. For this analysis, AAC was assessed by computed tomography of the abdomen from L3 to S1. Aortic calcium was scored using the Agatston method, and prevalence was defined as a score ≥10 to rule out false positives. Men also had BMD assessed using peripheral quantitative computed tomography at 4 % (trabecular vBMD) and 33 % (cortical vBMD) of the radius and tibia. RESULTS: Abdominal aortic calcification was present in 68.3 % of the men. Significant independent predictors of AAC prevalence were increased age, increased BMI, hypertension, and current smoking. Age was the strongest predictor, with each SD (7.8 year) increase in age conferring 2.7 times increased odds of having AAC (P < 0.0001). A one SD greater cortical, but not trabecular, vBMD was associated with a significant decreased odds of AAC prevalence independent of other traditional risk factors (OR 0.65; 95 % CI 0.45-0.92). CONCLUSIONS: Cortical vBMD is inversely associated with AAC presence. This finding suggests that there may be shared physiology between cortical bone compartment remodeling and vascular calcification.

Association analysis of 33 lipoprotein candidate genes in multi-generational families of African ancestry.

African ancestry individuals have a more favorable lipoprotein profile than Caucasians, although the mechanisms for these differences remain unclear. We measured fasting serum lipoproteins and genotyped 768 tagging or potentially functional single nucleotide polymorphisms (SNPs) across 33 candidate gene regions in 401 Afro-Caribbeans older than 18 years belonging to 7 multi-generational pedigrees (mean family size 51, range 21-113, 3,426 relative pairs). All lipoproteins were significantly heritable (P<0.05). Gender-specific analysis showed that heritability for triglycerides was much higher (P<0.01) in women than in men (women, 0.62+/-0.18, P<0.01; men, 0.13+/-0.17, P>0.10), but the heritability for LDL cholesterol (LDL-C) was higher (P<0.05) in men than in women (men, 0.79+/-0.21, P<0.01; women, 0.39+/-0.12, P<0.01). The top 14 SNPs that passed the false discovery rate threshold in the families were then tested for replication in an independent population-based sample of 1,750 Afro-Caribbean men aged 40+ years. Our results revealed significant associations for three SNPs in two genes (rs5929 and rs6511720 in LDLR and rs7517090 in PCSK9) and LDL-C in both the family study and in the replication study. Our findings suggest that LDLR and PCSK9 variants may contribute to a variation in LDL-C among African ancestry individuals. Future sequencing and functional studies of these loci may advance our understanding of genetic factors contributing to LDL-C in African ancestry populations.

Distinct distribution of HPV types among cancer-free Afro-Caribbean women from Tobago.

Human papillomavirus (HPV), a sexually transmitted virus causes cervical carcinomas, and is associated with approximately 36% of oropharyngeal tumours where HPV16 is the predominant genotype. The cervical cancer incidence rate in Trinidad and Tobago is about two times higher than the worldwide rate. We have for the first time determined the prevalence and type distribution of cervical HPV infections among cancer-free Afro-Caribbean women from Tobago, and compared it with the HPV subtypes observed in their oral cavity. Thirty-five per cent of the women were cervical HPV positive. The most common high-risk type detected in the cervix was HPV45 rather than HPV16 and 18. The prevalence of HPV infection in the oral mucosa was 6.6%. The distribution of HPV genotypes in healthy Tobagonian women is different from that reported in studies conducted in European and North American populations. This may have important implications for vaccine introduction in this and other Afro-Caribbean countries.

Estimates of African, European and Native American ancestry in Afro-Caribbean men on the island of Tobago

BACKGROUND/AIMS:The Tobago Afro-Caribbean population is a valuable resource for studying the genetics of diseases that show significant differences in prevalence between populations of African descent and populations of other ancestries. Empirical confirmation of low European and Native American admixture may help in clarifying the ethnic variation in risk for such diseases. We hypothesize that the degree of European and Native American admixture in the Tobago population is low.METHODS:Admixture was estimated in a random sample of 220 men, from a population-based prostate cancer screening survey of 3,082 Tobago males, aged 40 to 79 years. We used a set of six autosomal markers with large allele frequency differences between the major ethnic populations involved in the admixture process, Europeans, Native Americans and West Africans.RESULTS:The ancestral proportions of Tobago population are estimated as 94.0+/-1.2% African, 4.6+/-3.4% European and 1.4+/-3.6% Native American.CONCLUSIONS:We conclude that Tobago Afro-Caribbean men are predominantly of West African ancestry, with minimal European and Native American admixture. The Tobago population, thus, may carry a higher burden of high-risk alleles of African origin for certain diseases than the more admixed African-American population. Conversely, this population may benefit from a higher prevalence of protective alleles of African origin.

Association of body composition and physical activity with proximal femur geometry in middle-aged and elderly Afro-Caribbean men: the Tobago bone health study.

Osteoporotic fractures are less prevalent in African Americans than in caucasians, possibly because of differences in bone structural strength. Bone structural adaptation can be attributed to changes in load, crudely measured as lean and fat mass throughout life. The purpose of this analysis was to describe the associations of leg lean mass, total body fat mass, and hours walked per week with femoral bone mineral density (BMD) and bone geometry in a cross-sectional sample of 1,748 men of African descent between the ages of 40 and 79 years. BMD, section modulus (Z), cross-sectional area (CSA), and subperiosteal width were measured from dual energy X-ray absortiometry (DXA) scans using the hip structural analysis (HSA) program. Multiple linear regression models explained 35% to 48% of the variance in bending (Z) and axial (CSA) strength at the femoral neck and shaft. Independent of all covariates including total body fat mass, one standard deviation increase in leg lean mass was significantly associated with a 5% to 8% higher Z, CSA, and BMD (P < 0.010) at the neck and shaft. The number of hours walked per week was not a strong or consistent independent predictor of bone geometry or BMD. We have shown that weight is the strongest independent predictor of femur BMD and geometric strength although the effect appears to be mediated by lean mass since leg lean mass fraction and total body fat mass fraction had significant and opposing effects at the narrow neck and shaft in this group of middle aged and elderly men.

Positive predictive value (PPV) of prostate specific antigen (> ng/ml) and abnormal digital rectal exam for prostate cancer on the Caribbean island of Tobago

OBJECTIVE: To establish and compare the positive predictive values (PPV) for elevated (4 ng/ml) prostate specific antigen (PSA) and abnormal digital rectal exam (DRE) in an Afro-Caribbean population. DESIGN AND METHODS: We screened 728 men aged 40-79 years, recruited from the general population on the Caribbean island of Tobago. Ninety-five percent reported African ancestry. This population had not previously undergone screening for prostate cancer. RESULTS: PSA was elevated (> or = 4 ng/ml) and/or DRE was abnormal in 291 (40 percent) men. Pathological diagnosis of random sextant biopsies was completed in 191 (66 percent) of men. Ninety-two (13 percent) of the screened men were diagnosed with prostate cancer. Among men biopsied for abnormal DRE in the presence of normal PSA, PPV for abnormal DRE was 26 percent (11/43), range 9-50 percent across age groups. Among men with elevated PSA and normal DRE, the PPV for PSA was 46 percent (29/63), range 42-54 percent (no men aged 40-49 years (n=105) fell into this category). When all men with elevated PSA were considered, ignoring DRE status, PPV for PSA was 55 percent (79/144), range 50-60 percent. If both PSA and DRE were abnormal, the PPV was 63 percent. CONCLUSIONS: The PPV of abnormal DRE was similar to that observed in other populations undergoing screening for the first time. We speculate that a lower PSA cut-off point may be appropriate for optima ascertainment of cases in this high-risk population.(Au)

Blood pressure and echocardiographic measures in children of Tobago

OBJECTIVE: To ascertain blood pressure and echocardiographic measurements in Tobagonian children and to determine possible inter-relationships. DESIGN AND METHODS: Over the period 1994-1995, based on data from school enrolment in the area, we evaluated all the school children of Plymouth and Blackrock (n=338, 174 boys, 164 girls; age range 5-13 years). Anthropometric and blood pressure measurements were taken using WHO guidelines, and echocardiographic measurements of heart size were obtained according to the recommendations of the American Society of Echocardiography and the data were analysed. RESULTS: Echocardiographic indices of left heart size varied as a function of blood pressure levels. Male subjects demonstrated significantly higher adjusted left ventricular mass, left ventricular wall thickness, and left ventricular chamber size. After adjustment for body size, blood pressure correlated with left ventricular wall stress (p<0.001). Systolic blood pressure correlated with left ventricular mass (p<0.05), and height correlated with both systolic and diastolic blood pressure (p<0.01). CONCLUSIONS: Our data demonstrated that blood pressure in healthy Tobagonian children correlated with several measures of left ventricular size. Longitudinal studies are indicated.(Au)

Sodium-lithium countertransport activity is decreased after weight loss in healthy obese men.

Maximal red blood cell (RBC) sodium-lithium countertransport activity has been consistently related to essential hypertension and may be a marker for risk of developing hypertension. Although there is strong evidence for genetic control of sodium-lithium countertransport, increasing evidence suggests that obesity and insulin-glucose metabolism are related to countertransport activity. This study was performed to determine whether countertransport activity decreases with weight loss in healthy obese adults. Forty-five healthy, white, obese adults were studied at baseline and after 6 months of behavioral dietary intervention. Weight loss was 11.5 kg (25.4 lb) in 24 men and 8.1 kg (17.8 lb) in 21 women. Sodium-lithium countertransport activity decreased 55.0 mumol Li/L RBC/h in men (P < .001, paired t test) and 14.6 mumol Li/L RBC/h in women (NS). Change in countertransport activity was correlated with change in body mass index (BMI) in men (r = .52, P < .01) and women (r = .27, NS) and was also strongly correlated with change in fasting glucose levels in both men and women (r = .50 and r = .56, respectively; P < .01) and with change in fasting insulin levels in men (r = .42, P = .04). Change in countertransport activity was not significantly related to change in physical exercise or serum lipid levels. There was a large decrease in systolic blood pressure in men (10.0 mm Hg, P < .001) and a smaller decrease in women (4.1 mm Hg, P < .05). These changes were significantly correlated with change in weight, but not with change in countertransport or baseline countertransport activity.(ABSTRACT TRUNCATED AT 250 WORDS)