Norma McFarlane-Anderson

ACE, angiotensinogen and obesity: a potential pathway leading to hypertension.

The renin-angiotensin system (RAS) plays a crucial role in the regulation of fluid volume, thereby influencing blood pressure (BP). Obesity is an important risk factor for hypertension, however the physiologic basis for this relationship has not been clarified. In a population survey we examined the potential relationship between the RAS and obesity. Based on community sampling, 449 individuals were recruited from metropolitan Kingston, Jamaica. Serum angiotensin-converting enzyme (ACE) and circulating angiotensinogen levels were measured and the associated genes were typed for previously described polymorphisms. Obese individuals (body mass index >31) had significantly higher serum ACE and angiotensinogen levels, this relationship persisted for ACE in multivariate analyses controlling for BP, hypertension status, age, and gender. The insertion/deletion polymorphism of the ACE gene was associated with variation in the levels of ACE, but inconsistently with body mass index. Variants of the angiotensinogen gene leading to amino acid substitutions at positions 174 and 235 did not influence levels either of angiotensinogen or obesity. These data suggest that obesity may alter the levels of ACE and angiotensinogen, and provide a potential pathway through which obesity leads to elevation of BP.

Hypertension in four African-origin populations : current 'Rule of Halves', quality of blood pressure control and attributable risk of cardiovascular disease

Objective To assess the public health burden from high blood pressure and the current status of its detection and management in four African-origin populations at emerging or high cardiovascular risk. Design Cross-site comparison using standardized measurement and techniques. Setting Rural and urban Cameroon; Jamaica; Manchester, Britain. Subjects Representative population samples in each setting. African-Caribbeans (80% of Jamaican origin) and a local European sample in Manchester. Main outcome measures Cross-site age-adjusted prevalence; population attributable risk. Results Among 1587 men and 2087 women, age-adjusted rates of blood pressure ⩾ 160 or 95 mmHg or its treatment rose from 5% in rural to 17% in urban Cameroon, despite young mean ages, to 21% in Jamaica and 29% in Caribbeans in Britain. Treatment rates reached 34% in urban Cameroon, and 69% in Jamaican- and British- Caribbean-origin women. Sub-optimal blood pressure control (> 140 and 90 mmHg) on treatment reached 88% in European women. Population attributable risks (or fractions) indicated that up to 22% of premature all-cause, and 45% of stroke mortality could be reduced by appropriate detection and treatment. Additional benefit on just strokes occurring on treatment could be up to 47% (e.g. in both urban Cameroon men and European women) from tighter blood pressure control on therapy. Cheap, effective therapy is available. Conclusion With mortality risk now higher from non-communicable than communicable diseases in sub-Saharan Africa and elsewhere, systematic measurement, detection and genuine control of hypertension once treated can go hand-in-hand with other adult health programmes in primary care. Cost implications are not great. The data from this collaborative study suggest that such efforts should be well rewarded.

Relationship between maternal nutritional status and infant's weight and body proportions at birth

Objectives: To examine maternal nutritional status and its relationship to infant weight and body proportions.Design: Retrospective study of births from January–December 1990.Setting: University Hospital of the West Indies, Jamaica.Subjects: Records for 2394 live, singleton births, between 200–305 d gestation.Main outcome measures: Birth weight, crown heel length, head circumference, ponderal index, head circumference:length ratio, placental weight, placental:birth weight ratio.Results: Mothers who were lighter had babies who had lower birth weight, were shorter, had smaller heads and had a higher HC:L ratio. Shorter and thinner women had babies who had lower birth weights, were shorter, had smaller heads and lighter placentas. Thinner women also had babies with a lower placental:birth weight ratio, and their BMI’s were not linearly related to ponderal index and HC:L ratio. Women whose first trimester Hb levels were <9.5 g/dl had babies with the lowest birth weight, crown heel length, placental weight and ponderal index. These measurements increased as the Hb levels rose to 12.5 g/dl but then fell at Hb levels >12.5 g/dl. In the second and third trimester Hb levels were negatively associated with birth weight, crown heel length, head circumference, placenta weight and ponderal index.Conclusions: The data support the hypothesis that poor maternal nutrition is associated with foetal growth restraint. Poor maternal nutrition as indicated by low weight, height, and BMI are associated with smaller, shorter babies with smaller heads. Haemoglobin levels > 12.5 g/dl in pregnancy are associated with lighter, shorter, thinner babies, with smaller heads.

Polymorphisms of Renin-Angiotensin Genes Among Nigerians, Jamaicans, and African Americans

Within the context of an international collaborative study of the evolution of hypertension in the black diaspora, we determined the allelic distribution of hypertension candidate genes for the renin-angiotensin system in three populations of African origin. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) and the M235T and T174M variants of the angiotensinogen (AGT) gene were examined in individuals from Nigeria, Jamaica, and the United States. Large differences in the prevalence of hypertension were recorded in door-to-door surveys, ranging from 16% in Nigeria to 33% in the United States. The frequency of the D allele was similar in all groups (54%, 59%, and 63% in Nigeria, Jamaica, and the United States, respectively). The 235T allele of the AGT gene was found in 81% of US and Jamaican blacks and 91% of Nigerians; very little variation was seen for the T174M marker. Despite large differences in hypertension rates, genetic variation at the index loci among these groups was modest. Overall, the frequency of the ACE*D allele was only slightly higher than that reported for European and Japanese populations, whereas the AGT 235T allele was twice as common. Compared with blacks in the western hemisphere, Nigerians had a higher frequency of the 235T allele, which is consistent with 25% European admixture in Jamaica and the United States. The results indicate the potential for etiologic heterogeneity in genetic factors related to hypertension across ethnic groups while suggesting that environmental exposures most likely explain the gradient in risk in the comparison among black populations.

Blood Pressure Is Related to Placental Volume and Birth Weight

The objective of this study was to determine whether maternal nutrition and fetal and placental size program blood pressure. A longitudinal study linking the maternal anthropometric measurements of the first antenatal visit, ultrasound data of placental and fetal size, anthropometry at birth, and childhood growth and blood pressure was performed. The subjects were 428 women who attended the antenatal clinic at the University Hospital of the West Indies, Kingston, Jamaica, and their children, who were subsequently followed up. Systolic blood pressure at ages 1, 2, 2.5, 3, and 3.5 years was the main outcome measure. Pooling the data across ages, systolic blood pressure fell by 1.4 mm Hg for every 1-kg increase in birth weight (95% CI 0.2 to 2.7, P=0.02) and by 1.2 mm Hg for every 100-mL increase in placental volume at 20 weeks of gestation (95% CI 0.4 to 2.0, P=0.004). Blood pressure was also negatively associated with placental volume at 17 weeks and fetal abdominal circumference at 20 weeks. Measures of maternal nutritional status were strongly related to birth weight and placental volume but not directly to childhood blood pressure at these young ages. In conclusion, blood pressure is associated with fetal size in this population, as previously described among Europeans. We found associations between placental volume and abdominal circumference in the second trimester and childhood blood pressure, suggesting that the initiating events of blood pressure programming occur early in pregnancy. Measures of maternal nutritional status were not directly related to childhood blood pressure at these young ages but were strong predictors of both birth weight and placental volume, suggesting an indirect relation.

Diabetes in the Caribbean: results of a population survey from Spanish Town, Jamaica.

Aims To characterize the prevalence of diabetes and associated risk attributes in the Jamaican population.

Angiotensinogen and blood pressure among blacks: findings from a community survey in Jamaica

Objective To examine the association between blood pressure, angiotensinogen levels, angiotensin converting enzyme activity and polymorphisms of the angiotensinogen and angiotensin converting enzyme genes in a population-based sample. Method Five hundred participants were recruited in a house-to-house survey of three communities in metropolitan areas of Kingston and St Andrew, in Jamaica. Demographic data, anthropometric and blood pressure measurements were obtained for each participant during a brief clinic visit. Circulating levels of angiotensinogen and angiotensin converting enzyme activity were measured in venous blood samples. Polymorphisms of the angiotensinogen and angiotensin converting enzyme genes were determined. Results A weak association between angiotensinogen level, angiotensin converting enzyme activity and blood pressure was identified in this population, but substantial joint effect of angiotensin converting enzyme activity and angiotensinogen level on blood pressure was apparent Variants of the angiotensinogen gene had inconsistent effects on blood pressure and on the risk of hypertension. Angiotensinogen level and angiotensin converting enzyme activity were significantly related to several measures of obesity, including body mass index, waist circumference and skin fold thickness. Conclusion The angiotensinogen and angiotensin converting enzyme genetic variants which were studied appear to have only a modest relationship with blood pressure and associated anthropometric risk factors among blacks.

The angiotensin converting enzyme and blood pressure in Jamaicans.

An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme gene influences the level of serum angiotensin converting enzyme activity and has been associated with risk of several cardiovascular conditions. The relationship to blood pressure remains uncertain, however. We conducted a population-based survey in Kingston, Jamaica, to examine the association between angiotensin converting enzyme genotype, angiotensin converting enzyme serum activity and blood pressure. Serum angiotensin converting enzyme activity was measured and genotyping performed for the I/D polymorphism in 500 community residents. The overall prevalence of the D allele was 59.3%. Angiotensin converting enzyme genotype was not significantly related to blood pressure (P = .16), although it did influence angiotensin-converting enzyme activity, leading to an increase of 35% among individuals with the DD as compared with II genotype. Angiotensin converting enzyme levels were significantly higher in hypertensives as compared with normotensives (P < .05). A modest correlation was observed between blood pressure and angiotensin converting enzyme activity among untreated individuals (r = 0.11; P = .04), although this did not persist in multivariate analysis. A relationship between body mass index and angiotensin converting enzyme activity was identified in both men and women that was independent of genotype. These data demonstrate findings among blacks which are consistent with other studies and suggest a relationship between angiotensin converting enzyme genotype, and serum activity which is influenced by both genetic and environmental factors. The potential role of ACE on blood pressure control in the population remains uncertain.

Dietary intake of choline and plasma choline concentrations in pregnant women in Jamaica

Choline is an essential nutrient for humans and its availability during pregnancy is important for optimal fetal development. The Food and Nutrition Board of the Institute of Medicine in the United States of America has set the adequate choline intake during pregnancy at 450 mg/day. There is limited data available on normal plasma choline concentrations in pregnancy. Moreover, there are neither documented studies of choline intake among pregnant women in the Jamaican population nor of free plasma choline concentrations during pregnancy. Sixteen women presenting to the antenatal clinic of the University Hospital of the West Indies (UHWI) at 10-15 weeks of gestation were selected for this pilot study. A food frequency questionnaire was administered to estimate frequency of consumption of foods rich in choline. Fasting blood samples were collected by venepuncture and plasma assayed for choline using liquid chromatography electrospray ionization isotopic dilution mass spectrometry. Most of the women reported consumption of diets that delivered less than the recommended choline intake (mean +/- SEM, 278.5 +/- 28.9 mg). Mean plasma choline concentration was 8.4 +/- 0.4 micromol/L. This falls below the normal concentration (10 micromol/L) reported for individuals that are not pregnant and pregnant (14.5 micromol/L). The results of this study may be an indication that the choline included in the diet of pregnant women in Jamaica may not be adequate to meet both the needs of the mother and fetus and that further studies are warranted to determine clinical implications.

Early perturbations in keratin and actin gene expression and fibrillar organisation in griseofulvin-fed mouse liver

BACKGROUND/AIMS Long-term feeding of mice with a diet containing griseofulvin results in the formation of Mallory bodies, keratin K8 and K18 containing aggregates in hepatocytes. These bodies are biochemically and morphologically identical to the Mallory bodies that emerge in several human liver disorders. The aim of this study was to examine the contribution of K8 and K18 and actin to Mallory body formation. METHODS Mice were fed griseofulvin over a period ranging from 1 day to 20 months. Hepatocyte morphology was monitored by immunocytochemistry, gene expression by Northern and run-off transcription assays, and protein level by Western blotting. RESULTS Griseofulvin feeding induced a series of morphological alterations in hepatocytes that could be grouped into 3 phases: appearance of cholestasis during the first week (phase I), partial hepatocyte recovery at 3 months (phase II), and development of typical Mallory bodies after 3 to 5 months (phase III). All these cellular alterations were associated with perturbations in keratin and actin fibrillar status, coupled with increases in K8, K18 and actin mRNA steady-state level and, in K8 and K18 protein content. The transcriptional activity of the genes was not affected. CONCLUSIONS Perturbations in keratin and actin gene expression and fibrillar organisation constitute early events in the griseofulvin-induced pathological process that in the long-term leads to Mallory body formation. The higher keratin and actin mRNA levels reflect significant increases in mRNA stability taking place at the early phase of griseofulvin intoxication in hepatocytes.