Lizzy M. Brewster

Prognostic value of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters in patients with heart failure: a systematic review

AIMS To derive a more precise estimate of the prognostic significance of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters [early heart mediastinal ratio (H/M), late H/M, and myocardial washout] in heart failure (HF). METHODS AND RESULTS Eighteen studies with a total of 1755 patients, stratifying survival, and cardiac events in patients with HF by MIBG, were eligible for analysis. The pooled hazard ratio (HR) estimates for cardiac death and cardiac events associated with washout showed no significant heterogeneity and were 1.72 [95%CI (confidence interval), 1.72-2.52; P = 0.006] and 1.08 (95%CI: 1.03-1.12; P < 0.001), respectively. The pooled HR estimates for cardiac death and cardiac events associated with early H/M and late H/M showed significant heterogeneity (I2 > or = 75%). Limiting the pooling to the qualitative best three studies rendered I2 insignificant (I2 = 0) and resulted in a pooled HR of late H/M for cardiac death of 1.82 (95%CI: 0.80-4.12; P = 0.15) and for cardiac events of 1.98 (95%CI: 1.57-2.50; P < 0.001). CONCLUSION Our results indicate that patients with HF and decreased late H/M or increased myocardial MIBG washout have a worse prognosis compared with those with normal semi-quantitative myocardial MIBG parameters.

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001

Hypertension in Sub-Saharan Africa: Cross-Sectional Surveys in Four Rural and Urban Communities

Background Cardiovascular disease (CVD) is the leading cause of adult mortality in low-income countries but data on the prevalence of cardiovascular risk factors such as hypertension are scarce, especially in sub-Saharan Africa (SSA). This study aims to assess the prevalence of hypertension and determinants of blood pressure in four SSA populations in rural Nigeria and Kenya, and urban Namibia and Tanzania. Methods and Findings We performed four cross-sectional household surveys in Kwara State, Nigeria; Nandi district, Kenya; Dar es Salaam, Tanzania and Greater Windhoek, Namibia, between 2009–2011. Representative population-based samples were drawn in Nigeria and Namibia. The Kenya and Tanzania study populations consisted of specific target groups. Within a final sample size of 5,500 households, 9,857 non-pregnant adults were eligible for analysis on hypertension. Of those, 7,568 respondents ≥18 years were included. The primary outcome measure was the prevalence of hypertension in each of the populations under study. The age-standardized prevalence of hypertension was 19.3% (95%CI:17.3–21.3) in rural Nigeria, 21.4% (19.8–23.0) in rural Kenya, 23.7% (21.3–26.2) in urban Tanzania, and 38.0% (35.9–40.1) in urban Namibia. In individuals with hypertension, the proportion of grade 2 (≥160/100 mmHg) or grade 3 hypertension (≥180/110 mmHg) ranged from 29.2% (Namibia) to 43.3% (Nigeria). Control of hypertension ranged from 2.6% in Kenya to 17.8% in Namibia. Obesity prevalence (BMI ≥30) ranged from 6.1% (Nigeria) to 17.4% (Tanzania) and together with age and gender, BMI independently predicted blood pressure level in all study populations. Diabetes prevalence ranged from 2.1% (Namibia) to 3.7% (Tanzania). Conclusion Hypertension was the most frequently observed risk factor for CVD in both urban and rural communities in SSA and will contribute to the growing burden of CVD in SSA. Low levels of control of hypertension are alarming. Strengthening of health care systems in SSA to contain the emerging epidemic of CVD is urgently needed.

Is greater tissue activity of creatine kinase the genetic factor increasing hypertension risk in black people of sub-Saharan African descent?

We postulate that the genetic factor increasing the propensity of black people of sub-Saharan African descent to develop high blood pressure is the relatively high activity of creatine kinase, predominantly in vascular and cardiac muscle tissue. Such greater activity of creatine kinase has been reported in skeletal muscle of black untrained subjects has been reported to be almost twice the activity found in white subjects. Creatine kinase, a key enzyme of cellular energy metabolism, increases the capacity of the cell to function under high demands. The enzyme regulates, buffers and transports, via phosphocreatine and creatine, energy produced by glycolysis and oxidative phosphorylation to sites of energy consumption such as myofibrils and membrane ion pumps. At these cellular locations, it is involved in the contraction process and active trans-membranous transport by readily providing the ATP needed for these processes. In addition, creatine kinase is increasingly reported to be involved in trophic responses. Furthermore, by using H+ and ADP to synthesize ATP, creatine kinase prevents acidification of the cell, providing relative protection against the effects of ischaemia. Greater creatine kinase activity in cardiovascular muscle and other tissues with high energy demands could increase cardiovascular contractile reserve, enhance trophic responses and increase renal tubular ability to retain salt. This could facilitate the development of arterial hypertension under chronic provocative circumstances, with higher mean blood pressures, more left ventricular hypertrophy and relatively fewer ischaemic events. Therefore, greater cellular activity of creatine kinase might explain the greater hypertension risk and the clinical characteristics of hypertensive disease observed in the black population.

Why do hypertensive patients of African ancestry respond better to calciumblockers and diuretics than to ACE inhibitors and β-adrenergic blockers? Asystematic review

BackgroundClinicians are encouraged to take an individualized approach when treatinghypertension in patients of African ancestry, but little is known about whythe individual patient may respond well to calcium blockers and diuretics,but generally has an attenuated response to drugs inhibiting therenin-angiotensin system and to β-adrenergic blockers. Therefore, wesystematically reviewed the factors associated with the differential drugresponse of patients of African ancestry to antihypertensive drugtherapy.MethodsUsing the methodology of the systematic reviews narrative synthesis approach,we sought for published or unpublished studies that could explain thedifferential clinical efficacy of antihypertensive drugs in patients ofAfrican ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Foodand Drug Administration and European Medicines Agency databases weresearched without language restriction from their inception through June2012.ResultsWe retrieved 3,763 papers, and included 72 reports that mainly considered the4 major classes of antihypertensive drugs, calcium blockers, diuretics,drugs that interfere with the renin-angiotensin system and β-adrenergicblockers. Pharmacokinetics, plasma renin and genetic polymorphisms did notwell predict the response of patients of African ancestry toantihypertensive drugs. An emerging view that low nitric oxide and highcreatine kinase may explain individual responses to antihypertensive drugsunites previous observations, but currently clinical data are verylimited.ConclusionAvailable data are inconclusive regarding why patients of African ancestrydisplay the typical response to antihypertensive drugs. In lieu ofbiochemical or pharmacogenomic parameters, self-defined African ancestryseems the best available predictor of individual responses toantihypertensive drugs.

The effect of the creatine analogue beta-guanidinopropionic acid on energy metabolism: a systematic review.

Background Creatine kinase plays a key role in cellular energy transport. The enzyme transfers high-energy phosphoryl groups from mitochondria to subcellular sites of ATP hydrolysis, where it buffers ADP concentration by catalyzing the reversible transfer of the high-energy phosphate moiety (P) between creatine and ADP. Cellular creatine uptake is competitively inhibited by beta-guanidinopropionic acid. This substance is marked as safe for human use, but the effects are unclear. Therefore, we systematically reviewed the effect of beta-guanidinopropionic acid on energy metabolism and function of tissues with high energy demands. Methods We performed a systematic review and searched the electronic databases Pubmed, EMBASE, the Cochrane Library, and LILACS from their inception through March 2011. Furthermore, we searched the internet and explored references from textbooks and reviews. Results After applying the inclusion criteria, we retrieved 131 publications, mainly considering the effect of chronic oral administration of beta-guanidinopropionic acid (0.5 to 3.5%) on skeletal muscle, the cardiovascular system, and brain tissue in animals. Beta-guanidinopropionic acid decreased intracellular creatine and phosphocreatine in all tissues studied. In skeletal muscle, this effect induced a shift from glycolytic to oxidative metabolism, increased cellular glucose uptake and increased fatigue tolerance. In heart tissue this shift to mitochondrial metabolism was less pronounced. Myocardial contractility was modestly reduced, including a decreased ventricular developed pressure, albeit with unchanged cardiac output. In brain tissue adaptations in energy metabolism resulted in enhanced ATP stability and survival during hypoxia. Conclusion Chronic beta-guanidinopropionic acid increases fatigue tolerance of skeletal muscle and survival during ischaemia in animal studies, with modestly reduced myocardial contractility. Because it is marked as safe for human use, there is a need for human data.

Hypertension control in a large multi-ethnic cohort in Amsterdam, The Netherlands: The HELIUS study

OBJECTIVE Hypertension is a major problem among European ethnic minority groups. We assessed the current situation of hypertension prevalence and its management among a multi-ethnic population in Amsterdam, The Netherlands. METHODS Data from the HELIUS study were used including 12,974 participants (1871 Ghanaian, 2184 African Surinamese, 2278 South-Asian Surinamese, 2277 Turkish, 2222 Moroccan and 2142 Dutch origin people), aged 18-70 years. Comparisons among groups were made using proportions and age-adjusted prevalence ratios (PRs). RESULTS Hypertension prevalence ranged from 24% and 16% in Moroccan men and women to 52% and 62% in Ghanaian men and women. Except for Moroccan women, age-adjusted PR of hypertension was higher in all the ethnic minority groups than in Dutch. Among hypertensives, ethnic minority groups generally had higher levels of hypertension awareness and BP lowering treatment than Dutch. Moreover, prevalence rates for the prescription of more than one BP lowering drug were generally higher in African and South-Asian origin groups compared with Dutch origin people. By contrast, BP control levels were lower in all the ethnic groups than in Dutch, with control rates being significantly lower in Ghanaian men (26%, PR=0.49; 95% CI, 0.37-0.66) and women (45%, PR=0.64; 0.52-0.77), African-Surinamese men (30%, PR=0.61; 0.46-0.81) and women (45%, PR=0.72; 0.51-0.77), and South-Asian Surinamese men (43%, PR=0.77; 0.61-0.97) and women (47%, PR=0.76; 0.63-0.92) compared with Dutch men (53%) and women (61%). CONCLUSION Our findings indicate poor BP control in ethnic minority groups despite the high treatment levels. More work is needed to unravel the potential factors contributing to the poor control in order to improve BP control in ethnic minority groups, particularly among African and South-Asian origin groups.

Ethnic differences in tissue creatine kinase activity: An observational study

Background Serum creatine kinase (CK) levels are reported to be around 70% higher in healthy black people, as compared to white people (median value 88 IU/L in white vs 149 IU/L in black people). As serum CK in healthy people is thought to occur from a proportional leak from normal tissues, we hypothesized that the black population subgroup has a generalized higher CK activity in tissues. Methodology/Principal Findings We compared CK activity spectrophotometrically in tissues with high and fluctuating energy demands including cerebrum, cerebellum, heart, renal artery, and skeletal muscle, obtained post-mortem in black and white men. Based on serum values, we conservatively estimated to find a 50% greater CK activity in black people compared with white people, and calculated a need for 10 subjects of one gender in each group to detect this difference. We used mixed linear regression models to assess the possible influence of ethnicity on CK activity in different tissues, with ethnicity as a fixed categorical subject factor, and CK of different tissues clustered within one person as the repeated effect response variable. We collected post-mortem tissue samples from 17 white and 10 black males, mean age 62 y (SE 4). Mean tissue CK activity was 76% higher in tissues from black people (estimated marginal means 107.2 [95% CI, 76.7 to 137.7] mU/mg protein in white, versus 188.6 [148.8 to 228.4] in black people, p = 0.002). Conclusion We found evidence that black people have higher CK activity in all tissues with high and fluctuating energy demands studied. This finding may help explain the higher serum CK levels found in this population subgroup. Furthermore, our data imply that there are differences in CK-dependent ATP buffer capacity in tissue between the black and the white population subgroup, which may become apparent with high energy demands.

Function and Structure of Resistance Vessels in Black and White People

J Clin Hypertens (Greenwich). 2010;12:431–438. ©2010 Wiley Periodicals, Inc.

Effect of Health Insurance and Facility Quality Improvement on Blood Pressure in Adults With Hypertension in Nigeria A Population-Based Study

IMPORTANCE Hypertension is a major public health problem in sub-Saharan Africa, but the lack of affordable treatment and the poor quality of health care compromise antihypertensive treatment coverage and outcomes. OBJECTIVE To report the effect of a community-based health insurance (CBHI) program on blood pressure in adults with hypertension in rural Nigeria. DESIGN, SETTING, AND PARTICIPANTS We compared changes in outcomes from baseline (2009) between the CBHI program area and a control area in 2011 through consecutive household surveys. Households were selected from a stratified random sample of geographic areas. Among 3023 community-dwelling adults, all nonpregnant adults (aged ≥18 years) with hypertension at baseline were eligible for this study. INTERVENTION Voluntary CBHI covering primary and secondary health care and quality improvement of health care facilities. MAIN OUTCOMES AND MEASURES The difference in change in blood pressure from baseline between the program and the control areas in 2011, which was estimated using difference-in-differences regression analysis. RESULTS Of 1500 eligible households, 1450 (96.7%) participated, including 564 adults with hypertension at baseline (313 in the program area and 251 in the control area). Longitudinal data were available for 413 adults (73.2%) (237 in the program area and 176 in the control area). Baseline blood pressure in respondents with hypertension who had incomplete data did not differ between areas. Insurance coverage in the hypertensive population increased from 0% to 40.1% in the program area (n = 237) and remained less than 1% in the control area (n = 176) from 2009 to 2011. Systolic blood pressure decreased by 10.41 (95% CI, -13.28 to -7.54) mm Hg in the program area, constituting a 5.24 (-9.46 to -1.02)-mm Hg greater reduction compared with the control area (P = .02), where systolic blood pressure decreased by 5.17 (-8.29 to -2.05) mm Hg. Diastolic blood pressure decreased by 4.27 (95% CI, -5.74 to -2.80) mm Hg in the program area, a 2.16 (-4.27 to -0.05)-mm Hg greater reduction compared with the control area, where diastolic blood pressure decreased by 2.11 (-3.80 to -0.42) mm Hg (P = .04). CONCLUSIONS AND RELEVANCE Increased access to and improved quality of health care through a CBHI program was associated with a significant decrease in blood pressure in a hypertensive population in rural Nigeria. Community-based health insurance programs should be included in strategies to combat cardiovascular disease in sub-Saharan Africa.