The Use of Metabolomes in Risk Stratification of Heart Failure Patients: Protocol for a Scoping Review.

BACKGROUND: Heart failure (HF) is a significant health problem that is often associated with major morbidity and mortality. Metabolic abnormalities occur in HF and may be used to identify individuals at risk of developing the condition. Furthermore, these metabolic changes may play a role in the pathogenesis and progression of HF. Despite this knowledge, the utility of metabolic changes in diagnosis, management, prognosis, and therapy for patients with chronic HF has not been systematically reviewed. OBJECTIVE: This scoping review aims to systematically appraise the literature on metabolic changes in patients with HF, describe the role of these changes in pathogenesis, progression, and care, and identify knowledge gaps to inform future research. METHODS: This review will be conducted using a strategy based on previous reports, the JBI Manual for Evidence Synthesis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search of electronic databases (Medline, EBSCOhost, Scopus, and Web of Science) will be conducted using keywords related to HF, myocardial failure, metabolomes, metabonomics, and analytical chemistry techniques. The search will include original peer-reviewed research papers (clinical studies conducted on humans and systematic reviews with or without a meta-analysis) published between January 2010 and September 2023. Studies that include patients with HF younger than 18 years or those not published in English will be excluded. Two authors (UGA and MB) will screen the titles and abstracts independently and perform a full-text screen of the relevant and eligible papers. Relevant data will be extracted and synthesized, and a third author or group will be consulted to resolve discrepancies. RESULTS: This scoping review will span from January 2010 to September 2023, and the results will be published in a peer-reviewed, open-access journal as a scoping review in 2024. The presentation of the findings will use the PRISMA-ScR flow diagram and descriptive and narrative formats, including tables and graphical displays, to provide a comprehensive overview of the extracted data. CONCLUSIONS: This review aims to collect and analyze the available evidence on metabolic changes in patients with HF, aiming to enhance our current understanding of this topic. Additionally, this review will identify the most commonly used and suitable sample, analytical method, and specific metabolomes to facilitate standardization, reproducibility of results, and application in the diagnosis, treatment, and risk stratification of patients with HF. Finally, it is hoped that this review's outcomes will inspire further research into the metabolomes of patients with HF in low- and middle-income countries. TRIAL REGISTRATION: Open Science Framework; https://osf.io/sp6xj. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53905.

Heart failure with reduced ejection fraction and atrial fibrillation: a Sub-Saharan African perspective.

Cardiovascular diseases are a well-established cause of death in high-income countries. In the last 20 years, Sub-Saharan Africa (SSA) has seen one of the sharpest increases in cardiovascular disease-related mortality, superseding that of infectious diseases, including HIV/AIDS, in South Africa. This increase is evidenced by a growing burden of heart failure and atrial fibrillation (AF) risk factors. AF is a common comorbidity of heart failure with reduced ejection fraction (HFrEF), which predisposes to an increased risk of stroke, rehospitalizations, and mortality compared with patients in sinus rhythm. AF had the largest relative increase in cardiovascular disease burden between 1990 and 2010 in SSA and the second highest (106.4%) increase in disability-adjusted life-years (DALY) between 1990 and 2017. Over the last decade, significant advancements in the management of both HFrEF and AF have emerged. However, managing HFrEF/AF remains a clinical challenge for physicians, compounded by the suboptimal efficacy of guideline-mandated pharmacotherapy in this group of patients. There may be an essential role for racial differences and genetic influence on therapeutic outcomes of HFrEF/AF patients, further complicating our overall understanding of the disease and its pathophysiology. In SSA, the lack of accurate and up-to-date epidemiological data on this subgroup of patients presents a challenge in our quest to prevent and reduce adverse outcomes. This narrative review provides a contemporary overview of the epidemiology of HFrEF/AF in SSA. We highlight important differences in the demographic and aetiological profile and the management of this subpopulation, emphasizing what is currently known and, more importantly, what is still unknown about HFrEF/AF in SSA.

Twenty-four hour ambulatory blood pressure reference values in Africans.

OBJECTIVE: We aimed to establish reference values for 24 h ambulatory blood pressure (ABP) monitoring in an African community. PATIENTS AND METHODS: We randomly recruited 1219 participants of African ancestry from Soweto, a township in Johannesburg. Twenty-four hour ABP was measured using ABP monitors (model 90207; Spacelab). Complete 24 h ABP measurements from 530 healthy participants with a mean age of 38 were used to determine thresholds. RESULTS: Twenty-four hour, daytime and night-time systolic and diastolic BP increased significantly with age. The 95th prediction bands of this relation at age 38 years were ∼135/85 mmHg for 24 h, 140/90 mmHg for daytime and 130/80 mmHg for night-time ABP values, respectively. These thresholds and absolute ABP values are similar to those observed in individuals of other demographics. These thresholds increase with age by an average of 1.5 mmHg with each decade's increase in age. CONCLUSION: Pending authentication in prospective outcome-based studies, these values might be considered preliminary thresholds to diagnose hypertension in individuals of African descent.

Obesity masks the relationship between dietary salt intake and blood pressure in people of African ancestry: the impact of obesity on the relationship between sodium and blood pressure.

Previous studies conducted to investigate the relationship between sodium intake and blood pressure in our African population have yielded contradictory results. With the high prevalence of obesity in this population, it is possible that these contradictory findings are due to the masking effects of obesity on this relationship. We measured 24-hour ambulatory blood pressure and 24-hour urine excretion on 547 South Africans of African ancestry. A multivariate regression analysis revealed no independent relationship between 24-hour sodium excretion and blood pressure in the total population sample, but when participants were stratified according to body mass index (BMI) status, there was a significant association between 24-hour sodium excretion and blood pressure in the normal-BMI participants but not in the overweight/obese participants. We concluded that dietary salt intake, indexed by 24-hour urinary sodium excretion, was associated with increased ambulatory blood pressure but this relationship was masked because of a high proportion of overweight/obese individuals in this population.

Insulin resistance-associated decreases in left ventricular diastolic function are strongly modified by the extent of concentric remodeling in a community sample.

BACKGROUND: Whether excess adiposity, associated metabolic abnormalities or alternative risk factors for left ventricular (LV) diastolic function are modified rather than mediated by geometric LV remodeling, is uncertain. METHODS: Echocardiographic LV mass index (LVMI), relative wall thickness (RWT) and diastolic function (lateral and septal wall myocardial tissue lengthening at the level of the mitral annulus [e'] [n=430], ratio of early-to-late transmitral blood flow velocity (E/A), and E/e' [n=430]) were determined in 737 randomly recruited participants of a community-based study (43% obese). RESULTS: Independent of LVMI and confounders, indexes of adiposity and the homeostasis model of insulin resistance (HOMA-IR) were independently associated with LV diastolic function (p<0.05). In addition, RWT was independently associated with LV diastolic function (p<0.002). Importantly, an independent interaction between HOMA-IR and RWT, but not between blood pressure or age and RWT, was related to LV diastolic function (p<0.05). This translated into an independent relationship between HOMA-IR and lateral e' (partial r=-0.17, p<0.02), septal e' (partial r=-0.14, p=0.05), E/A (partial r=-0.17, p<0.005) and E/e' (partial r=0.19, p<0.01) in those with RWT above, but a lack of relationship between HOMA-IR and LV diastolic function (p>0.59) in those with RWT below the median for the sample. Similarly, HOMA-IR was independently associated with LV diastolic dysfunction in those with RWT above (p<0.05) but not below (p>0.19) the median for the sample. CONCLUSIONS: The relationship between insulin resistance, but not alternative risk factors and LV diastolic function is markedly modified by the presence of a more concentrically remodeled LV.

Intrafamilial aggregation and heritability of tissue Doppler indexes of left ventricular diastolic function in a group of African descent.

Although several indexes of left ventricular (LV) diastolic function show heritability, the genetic influence on the tissue Doppler index, E/e' (early transmitral velocity/velocity of myocardial tissue lengthening), an index of LV filling pressures in those of black African descent is currently unknown. Furthermore, whether any genetic influences on E/e' are through an impact of LV remodeling or aortic function is unknown. Intrafamilial aggregation and heritability (SAGE software) of E/e' (echocardiography) were assessed in 129 nuclear families (29 spouse pairs, 216 parent-child pairs, and 113 sibling-sibling pairs) from an urban developing community of black Africans, independent of LV mass index (LVMI), LV relative wall thickness (RWT), central aortic systolic pressure (SBPc), and backward wave pressures (Pb) (applanation tonometry, SphygmoCor software). Independent of confounders including LVMI and RWT, E/e' was correlated in parent-child (r = 0.23; P < .001) and sibling-sibling (r = 0.29; P < .005), but not in spouse (r = 0.13; P = .51) pairs. The relationships between parent-child (r = 0.22; P < .001) and sibling-sibling (r = 0.29; P < .005) pairs persisted with adjustments for SBPc. The relationships between parent-child (r = 0.22; P < .001) and sibling-sibling (r = 0.26; P < .01) pairs also persisted with adjustments for Pb. Independent of confounders including LVMI and RWT, E/e' showed significant heritability (h(2) ± standard error of the mean [SEM] = 0.51 ± 0.11; P < .0001) which similarly persisted with adjustments for SBPc (h(2) ± SEM = 0.50 ± 0.11; P < .0001) and Pb (h(2) ± SEM = 0.49 ± 0.11; P < .0001). In conclusion, in a group of African ancestry, independent of LV remodeling and aortic function, E/e' shows significant intrafamilial aggregation and robust heritability. Hence, genetic factors may play an important role in determining moderate-to-severe LV diastolic dysfunction independent of cardiac remodeling or aortic function in groups of black African ancestry.

Brachial Pressure Control Fails to Account for Most Distending Pressure-Independent, Age-Related Aortic Hemodynamic Changes in Adults.

BACKGROUND: Although several characteristics of aortic function, which are largely determined by age, predict outcomes beyond brachial blood pressure (BP), the extent to which brachial BP control accounts for age-related variations in aortic function is uncertain. We aimed to determine the extent to which brachial BP control in the general population (systolic/diastolic BP < 140/90 mm Hg) accounts for age-related aortic hemodynamic changes across the adult lifespan. METHODS: Central aortic pulse pressure (PPc), backward wave pressure (Pb), pulse wave velocity (PWV), and PP amplification (PPamp) (applanation tonometry and SphygmoCor software) were determined in 1,185 participants from a community sample (age >16 years; 36.4% uncontrolled BP). RESULTS: With adjustments for distending pressure (mean arterial pressure, MAP), no increases in PPc, Pb, or PWV and decreases in PPamp were noted in those with an uncontrolled brachial BP younger than 50 years. In those older than 50 years with an uncontrolled brachial BP, MAP-adjusted aortic hemodynamic variables were only modestly different to those with a controlled brachial BP (PPc, 46±14 vs. 42±15 mm Hg, P < 0.02, Pb, 23±8 vs. 21±8 mm Hg, PWV, 8.42±3.21 vs. 8.19±3.37 m/second, PPamp, 1.21±0.17 vs. 1.21±0.14). Nonetheless, with adjustments for MAP, marked age-related increases in PPc, Pb, and PWV and decreases in PPamp were noted in those with uncontrolled and controlled brachial BP across the adult lifespan (P < 0.0001). CONCLUSION: Brachial BP control in the general population fails to account for most distending pressure-independent, age-related changes in aortic hemodynamics across the adult lifespan.

Reflected rather than forward wave pressures account for brachial pressure-independent relations between aortic pressure and end-organ changes in an African community.

AIMS: To determine whether brachial blood pressure (BP)-independent relations between aortic pressure and cardiovascular damage are better explained by reflected (backward) (Pb) or forward (Pf) wave pressure effects. METHODS: In 1174 participants from a community of African ancestry, we assessed central aortic pulse pressure (PPc), Pb, and Pf (radial applanation tonometry, SphygmoCor) as well as left ventricular mass index (LVMI) (n = 786), aortic pulse wave velocity (PWV) (n = 1019), carotid intima-media thickness (IMT) (n = 578), transmitral early-to-late left ventricular diastolic velocity (E/A) (n = 779) and estimated glomerular filtration rate (eGFR) (n = 1174). RESULTS: Independent of mean arterial pressure and confounders, PPc, and both Pb and Pf were associated with end-organ measures or damage (P < 0.05 to P < 0.0001). With adjustments for brachial PP and confounders, Pb remained directly associated with LVMI (partial r = 0.09, P < 0.01), PWV (partial r = 0.28, P < 0.0001), and IMT (partial r = 0.28, P < 0.0001), and inversely associated with E/A (partial r = -0.31, P < 0.0001) and eGFR (partial r = -0.14, P < 0.0001). Similar relations were noted with the presence of end-organ damage (P < 0.05 to P < 0.0001). In contrast, with adjustments for brachial PP and confounders, Pf no longer retained direct relations with LVMI, PWV, and IMT or inverse relations with E/A and eGFR. Adjustments for Pb, but not Pf, diminished brachial PP-independent relationships between PPc and end-organ measures. Independent relations between Pb, but not Pf and end-organ measures, were largely attributed to Pb accounting for most of the variation in brachial-to-aortic PP amplification. CONCLUSIONS: In communities of African ancestry, brachial BP-independent relations between aortic pressure and end-organ changes are largely attributed to an impact of reflected rather than forward wave pressures.

Independent associations of circulating galectin-3 concentrations with aortic pulse wave velocity and wave reflection in a community sample.

Although the profibrotic inflammatory substance galectin-3 predicts outcomes in the general population, the mechanisms responsible for this effect are uncertain. We aimed to determine whether circulating galectin-3 concentrations are associated with carotid femoral (aortic) pulse wave velocity and aortic reflective wave index (applanation tonometry and SphygmoCor software) in 966 randomly selected participants from a community sample. Galectin-3 concentrations were not independently associated with office (n=966) or 24-hour (n=661) systolic (P=0.88-0.92) or diastolic (P=0.65-0.94) blood pressure. In contrast, with adjustments for age, sex (in all participants), office or 24-hour mean arterial pressure (or systolic blood pressure and pulse pressure), pulse rate, body mass index, regular smoking, regular alcohol intake, total cholesterol concentrations, diabetes mellitus or an glycohemoglobin >6.1%, treatment for hypertension, and estimated glomerular filtration rate, galectin-3 was independently associated with aortic pulse wave velocity in all participants (partial r=0.15, P<0.0001) and reflective wave index in men (partial r=0.13, P<0.02). In 745 participants who had never received antihypertensive therapy, galectin-3 concentrations were similarly independently associated with pulse wave velocity in all participants (partial=0.16, P<0.0001) and reflective wave index in men (partial r=0.15, P<0.02). The blood pressure-independent relations between galectin-3 concentrations and aortic hemodynamics persisted with further adjustments for C-reactive protein concentrations (pulse wave velocity in all participants: partial r=0.14, P<0.0001; reflective wave index in men: partial r=0.12, P<0.05). In conclusion, despite a lack of independent association with brachial blood pressure, the profibrotic inflammatory substance galectin-3 may contribute toward adverse outcomes through an effect on aortic stiffness, an effect that cannot be attributed to general inflammatory changes.

Intrafamilial aggregation and heritability of left ventricular geometric remodeling is independent of cardiac mass in families of African ancestry.

BACKGROUND: Whether left ventricular (LV) geometric remodeling, as indexed by relative wall thickness (RWT), aggregates in families and is inherited independent of LV mass (LVM) and additional confounders is uncertain. METHODS: We determined whether RWT as assessed from 2D targeted M-mode echocardiography shows intrafamilial aggregation and heritability independent of LVM in 181 nuclear families (73 spouse pairs, 403 parent-child pairs, and 177 sibling-sibling pairs) with 16 families including 3 generations from an urban developing community of black Africans. Intrafamilial aggregation and heritability estimates (S.A.G.E. software) were assessed independent of confounders, including central aortic systolic blood pressure (SBPc) (radial applanation tonometry and SphygmoCor software). RESULTS: Independent of confounders including SBPc, LV RWT was correlated in parent-child (r = 0.32, P < 0.0001) and sibling-sibling (r = 0.29, P < 0.0001), but not in spouse (r = 0.11, P = 0.33) pairs. The relationships between parent-child (r = 0.28, P < 0.0001) and sibling-sibling (r = 0.24, P < 0.001) pairs persisted with further adjustments for LVM or LVM indexed to height(2.7) (LVMI). Similarly, independent of confounders, LV RWT showed significant heritability (h(2) ± SEM = 0.56 ± 0.09, P < 0.0001) and this persisted with further adjustments for LVM (h(2) ± SEM = 0.48 ± 0.09, P < 0.0001) or LVMI (h(2) ± SEM = 0.49 ± 0.09, P < 0.0001). CONCLUSIONS: In a group of African ancestry, independent of LVM, LV geometric remodeling shows significant intrafamilial aggregation and heritability. Genetic factors may in-part determine the LV geometric remodeling process independent of the extent of cardiac hypertrophy.

Relative impact of blood pressure as compared to an excess adiposity on left ventricular diastolic dysfunction in a community sample with a high prevalence of obesity.

AIM: To determine whether blood pressure (BP) or an excess adiposity, both frequently observed comorbidities that independently relate to left ventricular diastolic dysfunction (LVDD), have a greater impact on LVDD at a community level. METHODS: We assessed the relative independent impact of an excess adiposity versus BP on indices of LVDD as determined from the ratios of early-to-late transmitral blood flow velocity (E/A) and E/the mean of lateral and septal wall myocardial tissue lengthening at the level of the mitral annulus (e'; (E/e') in 417 randomly recruited participants of a community-based study with a high prevalence of excess adiposity (43% obese and 25% morbidly obese). RESULTS: In multivariate adjusted models, including adjustments for appropriate BP values (SBP for E/e' and DBP for E/A), waist circumference was independently associated with E/A (partial r = -0.12, P < 0.02) and E/e' (partial r = 0.15, P < 0.005). In contrast, BMI was independently associated with E/e' (partial r = 0.11, P < 0.05), but not E/A (partial r = -0.09, P = 0.08). In multivariate models, SBP had a greater impact on E/e' (standardized ß-coefficient = 0.32 ±â€Š0.05, P < 0.0001) than did waist circumference (standardized ß-coefficient = 0.16 ±â€Š0.05, P < 0.005; P < 0.05 for comparison), whereas DBP had a similar impact on E/A (standardized ß-coefficient = -0.10 ±â€Š0.03, P < 0.005) as did waist circumference (standardized ß-coefficient = -0.10 ±â€Š0.04, P < 0.05). Importantly, whereas SBP was the main factor independently associated with an increased E/e' (≥10) (P < 0.0005), waist circumference was not independently associated with either a decreased E/A (≤0.75) (P = 0.82) or an increased E/e' (≥10; P = 0.15). CONCLUSION: In a community sample with a high prevalence of excess adiposity, BP exceeds obesity as the most important modifiable risk factor for LVDD. These data suggest that in communities with a high prevalence of obesity, if weight loss programmes fail to produce sustainable target body weights, rigorous BP management to lower than normal thresholds may be sufficient to prevent LVDD.

Intrafamilial aggregation and heritability of office-day blood pressure difference in a community of African ancestry: implications for genetic association studies.

OBJECTIVE: An inability to show consistent relationships between gene variants and blood pressure (BP) may be confounded by the use of office BP measurement. Whether the difference between office BP and day BP (office-day) is genetically predetermined is unknown. We therefore aimed to determine the intrafamilial aggregation and heritability of office-day BP. PATIENTS AND METHODS: Nurse-derived office BP (mean of 5 measurements according to guidelines) and 24-h ambulatory BP were determined for 592 participants from 198 families (67 spouse pairs, 361 parent-child pairs, and 169 sibling-sibling pairs), with 12 families having three generations, from an urban developing community of black Africans. Heritability estimates were determined using SAGE software. RESULTS: With adjustments for confounders, office systolic BP (SBP) (h=0.35±0.09, P<0.0001) showed comparable heritability estimates to 24-h SBP (h=0.33±0.09, P<0.0001). Similarly, with adjustments for confounders, office diastolic BP (DBP) (h=0.37±0.09, P<0.0001) showed comparable heritability estimates as 24-h DBP (h=0.35±0.09, P<0.0001). However, multivariate adjusted heritability estimates of day SBP (h=0.29±0.09, P<0.0001) and DBP (h=0.33±0.09, P<0.0001) were not diminished by further adjustments for office SBP (h=0.42±0.09, P<0.0001) or DBP (h=0.34±0.09, P<0.0001). Further, independent of confounders, office-day BP showed significant intrafamilial aggregation and heritability (SBP: h=0.51±0.10, P<0.0001; DBP: h=0.37±0.09, P<0.0001), effects that persisted with further adjustments for office, day, or day-night BP (P<0.0005 for SBP and DBP). CONCLUSION: Although office and ambulatory BP may show similar heritability estimates, genetic associations with carefully determined office BP measurements may be confounded by the heritability of office-day BP differences.

Left ventricular hypertrophy detection from simple clinical measures combined with electrocardiographic criteria in a group of African ancestry.

BACKGROUND: Whether routine clinical parameters associated with left ventricular mass (LVM) enhance the performance of electrocardiographic (ECG) criteria for LV hypertrophy (LVH) detection and hence modify overall cardiovascular risk stratification is unknown. METHODS: An approach to echocardiographic LVH detection was identified from ECG criteria and clinical variables [age, body mass index (BMI), systolic blood pressure (SBP) and estimated glomerular filtration rate] associated with LVM in 621 participants of African ancestry. Performance (area under the receiver operating curve) and classification accuracy for LVH detection and the impact on cardiovascular risk stratification were determined. RESULTS: Compared to Cornell criteria alone, the combined use of Cornell criteria and clinical variables increased the performance (p < 0.001) and sensitivity (p < 0.05 to p < 0.0001) for LVH detection. The use of Cornell product together with additional clinical parameters as compared to Cornell product criteria alone increased the proportion of participants with pre-, grade I or grade II hypertension risk stratified as having a high added cardiovascular risk (56.3-67.9 %, p < 0.05). CONCLUSIONS: In individuals of African ancestry, a combination of Cornell product criteria and age, BMI and SBP improves classification accuracy of Cornell criteria for LVH and increases those identified as having a high added as compared to lower cardiovascular risk scores.

Gender-specific contribution of aortic augmentation index to variations in left ventricular mass index in a community sample of African ancestry.

Although indices of aortic augmentation derived from radial applanation tonometry are independently associated with adverse cardiovascular effects, whether these relationships are influenced by gender is uncertain. We compared the brachial blood pressure-independent contribution of augmentation index (AIx) to variations in left ventricular mass index (LVMI) in a community sample of 808 participants, 283 of whom were men. Aortic haemodynamics were determined using radial applanation tonometry and SphygmoCor software and LVMI from echocardiography. In men, both AIx derived from aortic augmentation pressure/central aortic pulse pressure (AP/PPc; partial r = 0.17, ß-coefficient ± s.e.m. = 0.55 ± 0.20, P < 0.01) and AIx derived from the second peak/first peak (P2/P1) of the aortic pulse wave (partial r = 0.21, ß-coefficient ± s.e.m. = 0.42 ± 0.12, P<0.0005) were associated with LVM indexed to body surface area (LVMI-BSA). In contrast, in women, neither AIx derived from AP/PPc (partial r = -0.08, ß-coefficient ± s.e.m.=-0.20 ± 0.11, P = 0.08) nor AIx derived from P2/P1 (partial r = -0.06, ß-coefficient ± s.e.m. = -0.07 ± 0.05, P = 0.17) were associated with LVMI-BSA. Both the strength of the correlations (P<0.001 and P<0.0005 with z-statistics) and the slope of the AIx-LVMI relationships (P=0.001 and P<0.0005) were greater in men as compared with women. The lack of relationship between AIx and LVMI was noted in both premenopausal (n=285; AP/PPc vs. LVMI-BSA, partial r = 0.01, P = 0.95, P2/P1 vs. LVMI-BSA, partial r = 0.02, P = 0.77), and postmenopausal (n = 240; AP/PPc vs. LVMI-BSA, partial r = -0.06, P = 0.37, P2/P1 vs. LVMI-BSA, partial r = -0.03, P = 0.64) women. Similar differences were noted in the relationships between AIx and LVM indexed to height(2.7) in men and women. In conclusion, radial applanation tonometry-derived AIx may account for less of the variation in end-organ changes in women as compared with men.

Urinary angiotensinogen excretion is associated with blood pressure independent of the circulating renin-angiotensin system in a group of african ancestry.

Although the circulating renin-angiotensin system (RAS) is suppressed in salt-sensitive populations, the role of the intrarenal RAS in blood pressure (BP) control in these groups independent of the circulating RAS is uncertain. We evaluated the relationship between 24-hour urinary angiotensinogen excretion and either office (mean of 5 measurements; n=425) or 24-hour ambulatory (n=340) BP independent of the circulating RAS in a community-based sample of African descent that had never received antihypertensive drug therapy. Circulating RAS activity was determined from plasma renin and angiotensinogen and serum aldosterone concentrations. Urinary angiotensinogen to creatinine ratio (angiotensinogen/creat) was correlated with plasma angiotensinogen concentrations (P<0.0005) but not with indexes of salt intake. However, urinary angiotensinogen/creat was independently associated with office systolic BP (partial r=0.16; P<0.001), whereas plasma angiotensinogen (partial r=0.07; P=0.14) was not independently associated with office systolic BP. Urinary angiotensinogen/creat was also associated with 24-hour systolic BP (partial r=0.11; P<0.05). The relationships between urinary angiotensinogen/creat and BP survived further adjustments for plasma angiotensinogen and serum aldosterone concentrations, plasma renin concentrations, estimated glomerular filtration rate, urinary Na(+)/K(+), or 24-hour urinary Na(+) excretion rates (P<0.005 for all). Participants with the highest compared with the lowest quartile of urinary angiotensinogen/creat showed an 8.2-mm Hg higher office (P<0.005) and 4.6-mm Hg higher 24-hour (P=0.01) systolic BP. In conclusion, independent of the systemic RAS, including plasma angiotensinogen concentrations, urinary angiotensinogen excretion is associated with BP in a salt-sensitive, low-renin group of African descent. These data lend further support for a role of the RAS in BP control in salt-sensitive groups of African ancestry.

Differential relationships of systolic and diastolic blood pressure with components of left ventricular diastolic dysfunction.

AIMS: To determine whether SBP or DBP is best associated with different components of left ventricular diastolic dysfunction. METHODS: In 241 randomly selected participants, echocardiographic left ventricular diastolic function was assessed from early-to-atrial (E/A) transmitral velocity and E/e' where e' represents myocardial tissue lengthening velocity in early diastole as measured at the mitral annulus. Relationships between diastolic function and blood pressure (BP) were assessed from brachial and central aortic (radial applanation tonometry and SphygmoCor software) measurements. RESULTS: Independent of confounders, brachial DBP (partial r = -0.21, P < 0.002), but not SBP (partial r = -0.09, P = 0.18), was associated with E/A and the relationship between brachial DBP and E/A persisted with adjustments for brachial (P < 0.002) or aortic (P < 0.05) SBP. Although aortic SBP was independently associated with E/A, this relationship did not persist with adjustments for DBP (partial r = -0.05, P = 0.44). In contrast, both brachial (partial r = 0.34, P < 0.0001) and aortic (partial r = 0.34, P < 0.0001) SBP were independently associated with E/e', effects that persisted with adjustments for DBP (P < 0.0001), although independent relationships between DBP and E/e' did not persist with adjustments for brachial or aortic SBP (P = 0.17-0.57). In quartiles of DBP or SBP within normal-to-high normal ranges, multivariate adjusted E/A was decreased and E/e' increased as compared with those with optimal BP values (P < 0.05 to P < 0.005). CONCLUSION: Both SBP and DBP are important determinants of separate components of left ventricular diastolic dysfunction and these effects are noted even within normotensive BP ranges. DBP may be as important as SBP in the transition to diastolic dysfunction.

Chronic diseases are not being managed effectively in either high-risk or low-risk populations in South Africa.

BACKGROUND: Primary healthcare is the foundation of a country's healthcare system. Without an efficient and cost-effective programme, the level of healthcare offered across all levels of health management is adversely affected. OBJECTIVE: To analyse the effectiveness of the management of hypertension and diabetes mellitus (DM) among two distinct patient populations, one with significant cardiovascular risk factors and the other without. METHOD: We performed a case control study of a high-risk group of patients presenting with chronic critical limb ischaemia (CLI) to the Divisions of Vascular Surgery at Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital, and a randomly selected group of 'healthy' community participants from Johannesburg's South Western Townships (Soweto). RESULTS: We assessed 217 patients with CLI and 1 030 participants from the community. We assessed the number of patients who were not achieving their therapeuatic targets, among those known to be hypertensive (CLI: 44.7%; community: 59.9%) and diabetic (CLI: 83.5%; community: 66%). Undiagnosed diabetes affected 10.8% of patients with CLI and 11% of the community sample. CONCLUSION: Traditional vascular risk factors are managed poorly at both primary healthcare and at tertiary care levels. There is a need to identify factors that will address this issue.

Isolated increases in in-office pressure account for a significant proportion of nurse-derived blood pressure-target organ relations.

AIMS: We determined the extent to which relationships between nurse-derived blood pressures (BPs) and cardiovascular damage may be attributed to isolated increases in in-office SBP independent of ambulatory BP. METHODS: In 750 participants from a community sample, nurse-derived office BP, ambulatory BP, carotid-femoral pulse wave velocity (PWV; applanation tonometry and SphygmoCor software; n=662), and left ventricular mass indexed to height (LVMI; echocardiography; n=463) were determined. RESULTS: Nurse-derived office BP was associated with organ changes independent of 24-h BP (LVMI; partial r=0.15, P<0.005, PWV; partial r=0.21, P<0.0001) and day BP. However, in both unadjusted (P<0.0001 for both) and multivariate adjusted models (including adjustments for 24-h BP; LVMI; partial r=0.14, P<0.01, PWV; partial r=0.21, P<0.0001), nurse office-day SBP (an index of isolated increases in in-office BP) was associated with target organ changes independent of ambulatory BP and additional confounders, with the highest quartile (≥15 mmHg) showing the most marked increases in LVMI (P<0.0005) and PWV (P<0.0001) as compared to the lowest quartile (<-5 mmHg). These relationships were reproduced in those with normotensive day BP values and the quantitative effect of nurse office-day BP on target organ changes was at least equivalent to that of ambulatory BP. CONCLUSION: Nurse-elicited isolated increases in in-office BP account for a significant proportion of the relationship between nurse-derived BP and target organ changes independent of ambulatory BP. Therefore, high quality nurse-derived BP measurements do not approximate the impact of BP effects per se on cardiovascular damage.

Relations between white coat effects and left ventricular mass index or arterial stiffness: role of nocturnal blood pressure dipping.

BACKGROUND: Whether independent relationships between white coat effects (office minus day (office-day blood pressure (BP))) and organ damage or arterial stiffness may be explained by associations with an attenuated nocturnal BP dipping, has not been determined. METHODS: In 750 participants from a sample of African ancestry, office and 24-hour BP, carotid-femoral pulse wave velocity (PWV) (applanation tonometry and SphygmoCor software) (n = 662), and left ventricular mass indexed to height(2.7) (LVMI) (echocardiography) (n = 463) were determined. RESULTS: Office-day systolic BP (SBP) was correlated with day minus night (day-night) SBP, percentage night divided by day (night/day) SBP, and night SBP (P < 0.0005), and these relationships persisted with adjustments for confounders, including day SBP (P < 0.005). With adjustments for 24-hour SBP and additional confounders, office-day SBP was associated with LVMI (P < 0.01) and PWV (P < 0.0001). With adjustments for day SBP and additional confounders, day-night SBP, percentage night/day SBP, and night SBP were related to PWV (P < 0.05) but not to LVMI (P > 0.44). The relationships between office-day SBP and LVMI or PWV persisted with adjustments for either day-night or percentage night/day SBP (LVMI: P = 0.01; PWV: P < 0.0001) or night SBP (LVMI: P < 0.01; PWV: P = 0.0001), and in product of coefficient mediation analysis with appropriate adjustments, neither indexes of nocturnal BP dipping nor nocturnal BP per se contributed toward the impact of office-day BP on LVMI or PWV (P > 0.09). CONCLUSIONS: In a group of African ancestry, although white coat effects are independently associated with an attenuated nocturnal decrease in SBP, neither decreased BP dipping nor nocturnal BP contribute toward the independent relationships between white coat effects and LVMI or arterial stiffness.

Relationship between glomerular dysfunction and left-ventricular mass independent of haemodynamic factors in a community sample.

AIM: To evaluate whether the relationship between early glomerular dysfunction and left-ventricular mass (LVM) occurs in a community sample and whether this relationship depends on haemodynamic factors. METHODS: In 621 randomly selected participants from a community sample (332 were normotensive), estimated glomerular filtration rate (eGFR), LVM and dimensions were determined using echocardiography, and aortic blood pressure (BP) assessed from applanation tonometry and SphygmoCor software. Aortic pulse wave velocity (PWV) and high-quality 24-h BP values were available from 554 and 437 participants, respectively. RESULTS: With adjustments for confounders (including clinic SBP), eGFR was associated with LVM index (LVMI) and LVM in excess of that predicted from stroke work (inappropriate LVM, LVMinappr) in all participants (LVMI: partial r = -0.18, P < 0.0001; LVMinappr: partial r = -0.17, P < 0.0001) and normotensive (LVMI: partial r = -0.23, P < 0.0001; LVMinappr: partial r = -0.22, P < 0.0001) separate from hypertensive patients. Marked differences in LVMinappr were noted in the eGFR range below 132 compared to at least 132 ml/min per 1.73 m (P < 0.0005). When replacing clinic BP with either aortic SBP, 24-h BP, PWV, stroke work (for LVMI), left-ventricular end-diastolic diameter (LVEDD), or circumferential wall stress in the regression models, eGFR retained strong associations with LVMI (P = 0.01 to <0.0001) and LVMinappr (P < 0.005 to <0.0001) and these effects were replicated in normotensive separate from hypertensive patients. CONCLUSIONS: Strong relationships between eGFR and LVM occur at a community level irrespective of the presence of hypertension and independent of 24-h and aortic BP, PWV, LVEDD, stroke work and wall stress. Non-haemodynamic factors explain a considerable proportion of the relationship between early glomerular dysfunction and left-ventricular hypertrophy.