Marked Arterial Functional Changes in Patients With Arterial Vascular Events Across the Early Adult Lifespan.

OBJECTIVE: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P<0.0001), Zc (P<0.0005), and Pf (P<0.0001) were higher and early systolic pulse pressure amplification lower (P<0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P<0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. CONCLUSIONS: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

Carotid intima-media thickness, but not chronic kidney disease independently associates with noncardiac arterial vascular events in South Africa.

AIM: Although chronic kidney disease (CKD) as determined from estimated glomerular filtration rate (eGFR) is recommended for risk prediction by current hypertension guidelines, the equations to derive eGFR may not perform well in black Africans. We compared whether across the adult lifespan, eGFR or CKD are as closely associated with noncardiac arterial vascular events, as carotid intima-media thickness (IMT), in Africa. METHODS: In 1152 black South Africans [480 with noncardiac arterial events (294 with critical lower limb ischemia, 186 with stroke) of which 37% were premature] and 672 age, sex and ethnicity-matched controls from a randomly selected community sample, we assessed relations between eGFR, CKD or carotid IMT (B-mode ultrasound) and arterial events. RESULTS: From 20 years until old age, with or without adjustments, IMT was increased in those with as compared with without events (P < 0.01 at each decade of age). However, at any decade of age across the adult lifespan neither creatinine concentrations, nor eGFR were altered in those with arterial events (P > 0.28). Although IMT was strongly and independently associated with the odds of an event [odds ratio per 1 SD (0.171 mm) effect = 2.19, confidence interval = 1.75-2.78, P < 0.0001], neither creatinine concentrations (P = 0.89), modification of diet in renal disease-derived (P = 0.07), nor Chronic Kidney Disease Epidemiology Collaboration-derived [odds ratio per 1 SD (22.5 ml/min per 1.73 m) effect = 1.06, confidence interval = 0.89-1.27, P = 0.51] eGFR were independently associated with the odds of an event. Although many with premature events had an increased IMT (63%), few with either premature events (8%) or with events at an older age (21%) had CKD and CKD had a poor performance (0.539 ±â€Š0.011) and low sensitivity (16%) for event detection. CONCLUSION: In black South Africans, despite carotid IMT strongly associating with noncardiac arterial vascular events (stroke and critical lower limb ischaemia) consistently across the adult lifespan, few with events have CKD and CKD fails to associate with events.

Time to the peak of the aortic forward wave determines the impact of aortic backward wave and pulse pressure on left ventricular mass.

AIM: To determine the degree to which an extended time to the peak of the aortic forward wave or early wave reflection time enhance associations between aortic backward wave pressure and hence central aortic pulse pressure (PPc) and left ventricular mass index (LVMI). METHODS: In 701 adult participants from a community sample either receiving no antihypertensive therapy or receiving low-dose thiazide diuretic monotherapy for at least a year (the major therapy employed), we assessed aortic haemodynamics (SphygmoCor software and wave separation analysis; AtCor Medical, West Ryder, New South Wales, Australia) and LVMI (echocardiography). RESULTS: An interaction between time to the peak of the aortic forward wave and aortic backward wave pressure was independently associated with aortic augmented pressure (P < 0.01), PPc (P < 0.005), LVMI (P < 0.01), and LV hypertrophy (LVH; P = 0.01). The time to the peak of the aortic forward wave-aortic backward wave pressure interaction translated into a stepwise increase in the independent association between aortic backward wave pressure and aortic augmented pressure or PPc across quartiles of time to the peak of the aortic forward wave (P < 0.05 to < 0.0001 for comparison of slopes of relations). Furthermore, the time to the peak of the aortic forward wave-aortic backward wave pressure interaction translated into an increase in the independent association between PPc or aortic backward wave pressure and LVMI (P < 0.05 to < 0.001 for comparison of slopes and strength of relations) or LVH (P < 0.05 for comparisons of odds ratios), but not between forward wave pressures and LVMI or LVH across quartiles of time to the peak of the aortic forward wave. A markedly better ability of aortic backward wave pressure and PPc, but not forward wave pressures to detect LVH was noted in the highest as compared with the first three quartiles of time to the peak of the aortic forward wave (P < 0.05). In contrast, reflection time failed to influence the impact of aortic backward wave pressure or PPc on LVMI. CONCLUSIONS: Time to the peak of the aortic forward wave, but not early wave reflection markedly influences the impact of aortic backward wave pressure and hence aortic pulse pressure on LVMI and LVH in adults.

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.

Circulating resistin concentrations are independently associated with aortic pulse wave velocity in a community sample.

AIMS: The role of the adipokine, resistin in mediating increases in aortic stiffness is uncertain. We aimed to determine independent relations between circulating resistin concentrations and aortic pulse wave velocity (PWV) and wave reflection in a community-based sample with a high prevalence of untreated hypertension and obesity. METHODS: Plasma resistin, adiponectin, and C-reactive protein concentrations (ELISA); carotid-femoral (aortic) PWV and the aortic reflected wave index (applanation tonometry and SphygmoCor software) were determined in 683 randomly selected participants of African ancestry from SOWETO, South Africa who had never received antihypertensive therapy. RESULTS: Resistin concentrations were not independently associated with office or 24-h (n = 492) blood pressure (BP). In a stepwise regression model with BMI included in the model, age (P < 0.0001), mean arterial pressure (P < 0.0001), plasma resistin concentrations (P < 0.005), female sex (P = 0.01), and creatinine concentrations (P < 0.01) contributed independently to variations in PWV. Independent relations between resistin concentrations and PWV persisted with further adjustments for C-reactive protein concentrations (P < 0.005), and the homeostasis model of insulin resistance (P < 0.02). Similar relations were noted with waist circumference rather than BMI in the model. Resistin concentrations were not independently associated with aortic reflected wave index or aortic BP. CONCLUSION: Resistin is independently and directly associated with aortic stiffness and these effects occur beyond BP, insulin resistance, and general inflammation.

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 between resistin and left ventricular mass and myocardial dysfunction in a community sample with prevalent obesity.

BACKGROUND: Although the adipokine resistin may play a role in heart failure, the mechanisms of this effect are uncertain. Relations with left ventricular mass (LVM) and function are uncertain. METHODS: In 739 randomly selected participants from a community sample (43.6% obese), we assessed relations between circulating resistin concentrations and LVM index (LVMI), LVM beyond that predicted by stroke work (inappropriate LVMI [LVMinappr]) and systolic and diastolic LV function (echocardiography). RESULTS: Resistin concentrations were not independently associated with blood pressure (BP). However, resistin concentrations were associated with LVMI (partial r=0.12, p<0.0005), LVMinappr (partial r=0.18, p<0.0001) and LV hypertrophy (partial r=0.13, p<0.001) independent of BP, BMI, the homeostasis model of insulin resistance and additional confounders. Independent relations between resistin concentrations and LVMI and LVMinappr persisted with further adjustments for C-reactive protein concentrations. Resistin concentration (partial r=-0.12, p<0.002 in all and partial r=-0.15, p<0.0005 in untreated) was the only factor independently associated with LV midwall fractional shortening and these relations were enhanced at incremental concentrations of CRP. Resistin was not independently associated with transmitral and myocardial tissue Doppler indices of LV diastolic function. CONCLUSIONS: Resistin in-part explains variations in LVM, hypertrophy and myocardial systolic dysfunction, and these effects are independent of insulin resistance and 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.

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.

Aortic, but not brachial blood pressure category enhances the ability to identify target organ changes in normotensives.

AIMS: We sought to determine whether within normal/high-normal blood pressure (BP) ranges (120-139/80-89 mmHg), aortic BP may further refine BP-related cardiovascular risk assessment, as determined from target organ changes. METHODS: In 1169 participants from a community sample of African ancestry, 319 (27%) of whom had a normal/high-normal BP, aortic BP was determined using radial applanation tonometry and SphygmoCor software, and target organ changes assessed from carotid-femoral pulse wave velocity (PWV) (n = 1025), estimated glomerular filtration rate (eGFR) (n = 944), and left ventricular mass indexed to height (LVMI) (n = 690). RESULTS: Normal versus high-normal BP categories failed to differentiate between those participants with a BP above optimal values with versus without multivariate-adjusted target organ changes. However, in those with a normal/high-normal BP with aortic SBP values that were less than 95% confidence interval of healthy participants with optimal BP values (45% of those with a normal/high-normal BP), no unadjusted or multivariate adjusted target organ changes were noted. In contrast, those with a normal/high-normal BP with aortic SBP values that exceeded optimal thresholds, demonstrated unadjusted and multivariate adjusted increases in PWV and LVMI and decreases in eGFR (P < 0.05 to P < 0.005 after multivariate adjustments). CONCLUSION: In contrast to normal versus high-normal BP categories which do not clearly distinguish normotensives with from those without organ damage, noninvasively determined aortic BP measurements may refine the ability to detect those with a normal/high-normal BP at risk of BP-related cardiovascular damage.

Insulin resistance and the relationship between urinary Na(+)/K(+) and ambulatory blood pressure in a community of African ancestry.

BACKGROUND: Although groups of African descent are particularly sensitive to blood pressure (BP) effects of salt intake, the role of obesity and insulin resistance in mediating this effect is uncertain. We determined whether obesity or insulin resistance is independently associated with urinary Na(+)/K(+)-BP relationships in a community sample of African ancestry. METHODS: We measured 24-hour urinary Na(+)/K(+), homeostasis model assessment of insulin resistance (HOMA-IR), and nurse-derived conventional and 24-hour ambulatory BP in 331 participants from a South African community sample of black African descent not receiving treatment for hypertension. RESULTS: With adjustments for diabetes mellitus and the individual terms, an interaction between waist circumference and urinary Na(+)/K(+) was associated with day diastolic BP (P < 0.05) and an interaction between log HOMA-IR and urinary Na(+)/K(+) was associated with 24-hour and day systolic (P < 0.05) and 24-hour, day, and night diastolic (P < 0.002; P < 0.001) BP. The multivariable-adjusted relationship between urinary Na(+)/K(+) and night diastolic BP increased across tertiles of HOMA-IR (tertile 1: ß-coefficient = -0.79 ± 0.47; tertile 2: ß-coefficient = 0.65 ± 0.35; tertile 3: ß-coefficient = 1.03 ± 0.46; P < 0.05 tertiles 3 and 2 vs. 1). The partial correlation coefficients for relationships between urinary Na(+)/K(+) and 24-hour (partial r = 0.19; P < 0.02), day (partial r = 0.17; P < 0.05), and night (partial r = 0.18; P < 0.02) diastolic BP in participants with log HOMA-IR greater than or equal to the median were greater than those for relationships between urinary Na(+)/K(+) and 24-hour (partial r = -0.08; P = 0.29), day (partial r = -0.10; P < 0.22), and night (partial r = -0.06; P = 0.40) diastolic BP in participants with log HOMA-IR less than the median (comparisons of r values: P < 0.05). CONCLUSIONS: Insulin resistance may modify the relationship between salt intake, indexed by urinary Na(+)/K(+), and ambulatory BP in groups of African descent.