Association of Urinary Sodium Excretion and Left Ventricular Hypertrophy in People With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: It has been well documented that left ventricular hypertrophy (LVH) is highly associated with the incidence of cardiovascular disease (CVD). Evidence indicated that high sodium intake was closely related with LVH in general population. However, information is not available regarding the association between urinary sodium excretion and LVH in patients with type 2 diabetes mellitus (T2DM). This study aimed to explore the association between urinary sodium excretion and LVH in patients with T2DM. Methods: This cross-sectional analysis included baseline data from 1,556 individuals with T2DM enrolled in the NanFang Prospective Diabetes Study (NFPDS). Urinary sodium excretion levels were measured from 24-hour urine samples of inpatients and morning fasting urine samples of outpatients. Left ventricular dimensions were assessed by echocardiography. The associations between urinary sodium excretion and the risks of cardiovascular events, LVH and left ventricular mass index (LVMI) were examined using linear regression analysis, logistic regression and restricted cubic splines (RCS). Results: Urinary sodium excretion levels were positively associated with cardiometabolic risk factors, including systolic blood pressure, body mass index, waist circumference and LVMI (All P<0.001). Odds ratios of the highest quartile of urinary sodium excretion compared with the lowest quartile were 1.80 (95% CI, 1.28-2.54; P=0.001) for LVH and 1.77 (95% CI, 1.06-2.94; P=0.028) for CVD, after adjusted for demographics, lifestyle risk factors and cardiovascular risk factors. Multivariable-adjusted RCS analysis of the association between urinary sodium excretion and LVMI showed a significant association (P=0.001) and lacked evidence of a nonlinear association (P=0.406). Conclusion: This study indicated that high urinary sodium excretion was independently associated with increased risk of LVH and CVD in patients with T2DM, suggesting that control of sodium intake may be valuable for the prevention of diabetic cardiovascular complications.

Increased epicardial adipose tissue thickness is associated with microalbuminuria in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: Epicardial adipose tissue (EAT) is a cardiometabolic risk factor, and its possible relationship with hypertension has been previously reported. Microalbuminuria (MA) is associated with target-organ damage, especially in patients with hypertension with left ventricular hypertrophy (LVH) and suggest endothelial dysfunction. This study aimed to investigate the relationship between echocardiographic EAT thickness and presence of MA in patients with hypertension. METHODS: A total of 297 newly diagnosed hypertension patients who applied to the outpatient clinic were enrolled consecutively in this study. Patients were divided into two groups regarding the presence of LVH in echocardiography. An age and gender matched control group was set including 156 healthy patients without HT. All subjects underwent transthoracic echocardiography for the measurement of EAT thickness. Spot urine samples were collected for the assessment of MA. RESULTS: In hypertensive patients with LVH, the EAT thicknesses (6.6 ± 1.8 vs 5.3 ± 1.5 vs 5.1 ± 1.3, p < .001; respectively) and prevalence of MA (41.2 vs 20.1 vs 3.2%; p < .001 respectively) were significantly higher than the other two groups. In hypertensive patiens without LVH, no relationship was found between the presence of MA and EAT thickness. In multivariate regression analyses, EAT thickness (OR: 3.141, 95%CI: 2.425-6.123, p < .001) and left ventricular mass index (OR: 1.339, 95%CI: 1.145-2.143, p = .003) were determined as independent predictors for MA development in hypertensive patients with LVH. CONCLUSION: Measurement of EAT thickness may help to identify high-risk hypertensive patients for target-organ damage especially among patients with LVH.

Left ventricular mass independently associates with 24-hour sodium excretion in young masked hypertensive adults: The African-PREDICT study.

BACKGROUND: Due to the known contribution of excess sodium intake on elevations in blood pressure, salt reduction regulations are being introduced in countries all over the world. To study the contribution of sodium intake on cardiovascular disease development, we determined whether left ventricular mass associates with sodium excretion in young adults free from overt cardiovascular disease and those with masked hypertension. METHODS: We included 681 participants (41% men and 50% black) in a cross-sectional analysis from the African-PREDICT study with complete 24-hour urine collections and successful ambulatory blood pressure monitoring (>70% valid readings). The participants were categorized as normotensive (n = 534) or masked hypertensive (n = 147). In addition, we determined left ventricular mass index (LVMI) along with traditional risk factors. RESULTS: Masked hypertensive individuals had higher sodium excretion (149 vs. 128 mmol/L/day) and LVMI (78.1 vs. 69.6 g/m2) than normotensives. In single, partial and multiple regression analyses, LVMI independently associated with higher sodium excretion in the total group of young adults (ß = 0.089; p = 0.011). This result was also evident among masked hypertensives (ß = 0.215; p = 0.008), but not in normotensives (ß = 0.054; p = 0.134). CONCLUSION: Our results indicated that higher sodium excretion (reflecting a higher salt intake) may contribute to increased left ventricular mass, potentially driven by the early development of masked or undetected hypertension.

Changes in serum and intracardiac fibroblast growth factor 23 during the progression of left ventricular hypertrophy in hypertensive model rats.

BACKGROUND: Recent clinical studies have demonstrated that serum fibroblast growth factor 23 (FGF23) levels have a significant association with left ventricular hypertrophy (LVH). Although LVH is commonly seen in hypertensive patients, the association between FGF23, hypertension, and LVH remains unclear. We aimed to examine the changes in serum and intracardiac FGF23 during the progression of hypertension using spontaneously hypertensive rats (SHR). METHODS: Male SHR comprised the experimental group (HT group) and Wistar Kyoto rats served as controls. At 10 weeks, urinary and blood biochemical analyses and blood pressure measurements were performed for both the groups. At 18 weeks, the rats were sacrificed: urinary and blood biochemical analyses and real-time PCR were performed. RESULTS: At 18 weeks, the relative heart weight and serum N-terminal pro-brain natriuretic peptide and aldosterone levels were significantly greater in the HT group. Serum calcium and phosphate levels were significantly lower, while serum FGF23 levels were significantly higher in the HT group compared to the control group. Further analyses showed that the mRNA expression of FGF23 in the heart was significantly increased in the HT group compared to the control group. Both serum FGF23 levels and intracardiac mRNA expression of FGF23 showed significant correlation with the relative heart weight. CONCLUSIONS: During LVH progression, serum and intracardiac FGF23 increased in hypertension. Although it is unclear whether the change in FGF23 is the cause or result of LVH, the interaction between FGF23 and aldosterone may be associated with the development of LVH in hypertension.

Urinary angiotensinogen level is increased in renal transplant recipients with masked hypertension and is correlated with left ventricular mass index and albuminuria in these patients.

Activation of the local renin-angiotensin system (RAS) is an independent risk factor for the development of proteinuria and left ventricular hypertrophy (LVH) more commonly seen in masked hypertensives. It has been reported that urinary angiotensinogen (UAGT) level provides a specific index of the intrarenal RAS status. The aim of this study was to evaluate the association between UAGT and left ventricular mass index (LVMI) and urinary albumin-creatinine ratio (UACR) in renal transplant recipients (RTRs) with masked hypertension (HT). A total of 116 non-diabetic-treated hypertensive RTRs were included in this study. The patients were divided into two groups: masked hypertensives and controlled hypertensives. Forty-two (36.2%) of RTRs had masked HT. Mean UACR and LVMI levels were higher in RTRs with masked HT than in RTRs with controlled HT (P < 0.001). UAGT level was also higher in masked hypertensives compared to controlled hypertensives (P < 0.001). Multivariable regression analysis showed that UAGT was positively correlated with UACR (ß = 0.024, P = 0.001) and LVMI (ß = 0.082, P = 0.001) in masked hypertensives. Consequently, masked HT was considerably frequent (36.2%) in treated hypertensive RTRs and high UAGT levels accompanied by high albuminuria and LVMI levels were seen in these patients. Overproduction of the UAGT may play a pivotal role in the development of LVH and proteinuria in masked hypertensives.

Marinobufagenin and left ventricular mass in young adults: The African-PREDICT study.

Background The endogenous steroidal inhibitor of sodium-potassium-dependent adenosine triphosphate and natriuretic hormone, marinobufagenin, plays a physiological role in ionic homeostasis. Animal models suggest that elevated marinobufagenin adversely associates with cardiac and renal, structural and functional alterations. It remains uncertain whether marinobufagenin relates to the early stages of target organ damage development, especially in young adults without cardiovascular disease. We therefore explored whether elevated 24-hour urinary marinobufagenin excretion was related to indices of subclinical target organ damage in young healthy adults. Design This cross-sectional study included 711 participants from the African-PREDICT study (black 51%, men 42%, 24.8 ± 3.02 years). Methods We assessed cardiac geometry and function by two-dimensional echocardiography and pulse wave Doppler imaging. 24-Hour urinary marinobufagenin and sodium excretion were measured, and the estimated glomerular filtration rate determined. Results Across marinobufagenin excretion quartiles, left ventricular mass ( P < 0.001), end diastolic volume ( P < 0.001), stroke volume ( P = 0.004) and sodium excretion ( P < 0.001) were higher within the fourth compared with the first quartile. Partial regression analyses indicated that left ventricular mass ( r = 0.08, P = 0.043), end diastolic volume ( r = 0.10, P = 0.010) and stroke volume ( r = 0.09, P = 0.022) were positively related to marinobufagenin excretion. In multivariate-adjusted regression analysis, left ventricular mass associated positively with marinobufagenin excretion only in the highest marinobufagenin excretion quartile (adjusted R2 = 0.20; ß = 0.15; P = 0.043). This relationship between left ventricular mass and marinobufagenin excretion was evident in women (adjusted R2 = 0.06; ß = 0.127; P = 0.015) but not in men (adjusted R2 = 0.06; ß = 0.007; P = 0.92). Conclusions Left ventricular mass positively and independently associates with marinobufagenin excretion in young healthy adults with excessively high marinobufagenin excretion. Women may be more sensitive to the effects of marinobufagenin on early structural cardiac changes.

Albuminuria and kidney function as prognostic marker of left ventricular mass among South Asians with hypertension.

We aimed to evaluate the association of albuminuria and estimated glomerular filtration rate (eGFR) at baseline and changes in these parameters with left ventricular mass index (LVMI) at 7 years in adults with hypertension from communities in Pakistan. A nested cohort of 539 hypertensives aged 40 years and older from a community-living population in Karachi, Pakistan, followed up for 7 years in the Control of Blood Pressure and Risk Attenuation trial. Urine spot albumin-to-creatinine ratio (UACR) and serum creatinine-based eGFR were assessed at baseline and 7 years, and echocardiography at 7 years. Mean age of participants was 50.9 ± 9.1 (standard deviation) years; 63% were female. Mean eGFR was 91.0 ± 15.9 (standard deviation) mL/min/1.73 m2 and median (interquartile range) UACR 6.2 (3.9, 11.3) mg/g. In multivariate analysis, although baseline eGFR was marginally associated with LVMI, a strong association was found between higher LVMI with greater rate of decline in eGFR (ß = -1.05; 95% confidence interval [CI]: [-1.94, -0.17]). Higher baseline UACR was significantly associated with higher follow-up LVMI (ß = 2.26; 95% CI: [0.87, 3.65]), as was rate of UACR increase of ≥1.07 mg/g/y versus of <0.14 mg/g/y. (ß = 4.19; 95% CI: [0.75, 7.63]). Associations with developing left ventricular hypertrophy were found for reduced baseline eGFR, higher baseline UACR, and greater rate of UACR increase, but not for rate of eGFR decline. Comparable results were observed for the outcomes of posterior wall thickness and septal wall thickness. Higher baseline albuminuria, lower baseline eGFR, and their longitudinal worsening were significantly associated with higher LVMI or the development of left ventricular hypertrophy among individuals with hypertension in Pakistan.

Cardiac Troponin T as Early Marker of Subclinical Cardiovascular Deterioration in Black Hypertensive Women.

BACKGROUND: Hypertensive heart disease is a rising concern, especially among black South African women. As high sensitivity cardiac troponin T (cTnT) is a marker of cardiomyocyte damage, we determined the potential link of (i) systemic endothelial dysfunction (reflected by urinary albumin-to-creatinine ratio), (ii) large artery stiffness, (iii) cardiac volume load (estimated by the N-terminal prohormone B-type natriuretic peptide (Nt-proBNP)), and (iv) ECG left ventricular hypertrophy in post-menopausal black women. METHODS: In 121 (50 normotensive and 71 hypertensive) black women (mean age: 60.6 years), basic cardiovascular assessments including blood pressure and ECG were performed, along with plasma and urinary biomarkers including cTnT. RESULTS: The cTnT levels (p=0.049) along with Nt-proBNP (p=0.003), pulse pressure (p<0.0001) and the Cornell product (p=0.030) were higher in hypertensive than normotensive women. Only in hypertensive women, was cTnT independently associated with urinary albumin-to-creatinine ratio (ß=0.25; p=0.019), pulse pressure (ß=0.31; p=0.019), Nt-proBNP (ß=0.47; p<0.0001) and Cornell product (ß=0.31; p=0.018). An independent association between albumin-to-creatinine ratio and cTnT was also evident in normotensive women (ß=0.34; p=0.037). CONCLUSION: We found cTnT to be a useful marker in an elderly black population relating to several measures of cardiovascular deterioration - from subclinical endothelial dysfunction to left ventricular hypertrophy.

Resistance to hypertension and high Cl- excretion in humans with SLC26A4 mutations.

Pendrin is a membrane transporter encoded by solute carrier family26A4 (SLC26A4). Mutations in this gene are known to cause hearing loss, and recent data from animal studies indicate a link between pendrin expression and hypertension; although, this association in humans is unclear. To clarify this issue, we investigated the influence of pendrin on blood pressure by analyzing demographic and biochemical data - including blood pressure and urinary electrolyte excretion - in patients with bi-allelic SLC26A4 mutations. Systolic and diastolic blood pressure and the left ventricular hypertrophy index were lower in subjects with pendrin mutations than in controls. In addition, fractional excretion of Na+ and Cl- was increased and serum renin, angiotensin I and II levels were higher in subjects with pendrin mutations as compared to controls. Thus, patients with impaired pendrin function are likely to be resistant to high blood pressure due to enhanced urinary Na+ /Cl- excretion. These results suggest that pendrin may regulate blood pressure through increased urinary salt excretion.

Screening for Fabry Disease by Urinary Globotriaosylceramide Isoforms Measurement in Patients with Left Ventricular Hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a frequent echocardiographic feature in Fabry disease (FD) and in severe cases may be confused with hypertrophic cardiomyopathy (HCM) of other origin. The prevalence of FD in patients primarily diagnosed with HCM varies considerably in screening and case finding studies, respectively. In a significant proportion of patients, presenting with only mild or moderate LVH and unspecific clinical signs FD may remain undiagnosed. Urinary Gb3 isoforms have been shown to detect FD in both, women and men. We examined whether this non-invasive method would help to identify new FD cases in a non-selected cohort of patients with various degree of LVH. METHODS AND RESULTS: Consecutive patients older than 18 years with a diastolic interventricular septal wall thickness of ≥12mm determined by echocardiography were included. Referral diagnosis was documented and spot urine was collected. Gb3 was measured by mass spectroscopy. Subjects with an elevated Gb3-24:18 ratio were clinically examined for signs of FD, α-galactosidase-A activity in leukocytes was determined and GLA-mutation-analysis was performed. We examined 2596 patients. In 99 subjects urinary Gb3 isoforms excretion were elevated. In these patients no new cases of FD were identified by extended FD assessment. In two of three patients formerly diagnosed with FD Gb3-24:18 ratio was elevated and would have led to further diagnostic evaluation. CONCLUSION: Measurement of urinary Gb3 isoforms in a non-selected cohort with LVH was unable to identify new cases of FD. False positive results may be prevented by more restricted inclusion criteria and may improve diagnostic accuracy of this method.

Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year 25. PREDICTOR: eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). OUTCOME: LVMI measured at year 25. MEASUREMENTS: We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. RESULTS: Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n = 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n = 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (ß coefficient, 1.48; 95% CI, 0.11-2.83; P = 0.03) after adjustment for confounders. LIMITATIONS: There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). CONCLUSIONS: Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated LVMI in this range of eGFRcys.

Regression of left ventricular hypertrophy and microalbuminuria changes during antihypertensive treatment.

OBJECTIVE: The objective of the present study was to assess the regression of left ventricular hypertrophy (LVH) during antihypertensive treatment, and its relationship with the changes in microalbuminuria. INDIVIDUALS AND METHODS: One hundred and sixty-eight previously untreated patients with echocardiographic LVH, 46 (27%) with microalbuminuria, were followed during a median period of 13 months (range 6-23 months) and treated with lifestyle changes and antihypertensive drugs. Twenty-four-hour ambulatory blood pressure monitoring, echocardiography and urinary albumin excretion were assessed at the beginning and at the end of the study period. RESULTS: Left ventricular mass index (LVMI) was reduced from 137 [interquartile interval (IQI), 129-154] to 121 (IQI, 104-137) g/m (P < 0.001). Eighty-nine patients (53%) had a reduction in LVMI of at least 17.8 g/m, and an LVH regression rate of 43.8 per 100 patient-years [95% confidence interval (CI) 35.2-53.9]. The main factor related to LVH regression was the reduction in SBP24 h [multivariate odds ratio (ORm) 4.49; 95% CI 1.73-11.63; P = 0.005, highest tertile compared with lower tertiles]. Male sex (ORm 0.39; 95% CI 0.17-0.90; P = 0.04) and baseline glomerular filtration rate less than 90 ml/min per 1.73 m (ORm 0.39; 95% CI 0.17-0.90; P = 0.03) were associated with a lower probability of LVH regression. Patients with microalbuminuria regression (urinary albumin excretion reduction >50%) had the same odds of achieving regression of LVH as patients with normoalbuminuria (ORm 1.1; 95% CI 0.38-3.25; P = 0.85). However, those with microalbuminuria at baseline, who did not regress, had less probability of achieving LVH regression than the normoalbuminuric patients (OR 0.26; 95% CI 0.07-0.90; P = 0.03) even when adjusted for age, sex, initial LVMI, GFR, blood pressure and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) treatment during the follow-up. CONCLUSION: Patients who do not have a significant reduction in microalbuminuria have less chance of achieving LVH regression, independent of blood pressure reduction.

Twenty-four-hour urinary aldosterone predicts inappropriate left ventricular mass index in patients with primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is associated with inappropriate left ventricular hypertrophy (LVH) in relation to a given gender and body size. There is no ideal parameter to predict the presence of LVH or inappropriate LVH in patients with PA. We investigate the performance of 24-hour urinary aldosterone level, plasma renin activity and aldosterone-to-renin ratio on this task. METHODS: We performed echocardiography in 106 patients with PA and 31 subjects with essential hypertension (EH) in a tertiary teaching hospital. Plasma renin activity, aldosterone concentration, and 24-hour urinary aldosterone level were measured. RESULTS: Only 24-hour urinary aldosterone was correlated with left ventricular mass index (LVMI) and excess LVMI among these parameters. The multivariate analysis revealed the urinary aldosterone level as an independent predictor for LVMI and excess LVMI. Analyzing the ability of urinary aldosterone, plasma aldosterone concentration, and plasma aldosterone-to-renin ratio to identify the presence of LVH (ROC AUC = 0.701, 0.568, 0.656, resp.) and the presence of inappropriate LV mass index (defined as measured LVMI in predicting LVMI ratio >135%) (ROC area under curve = 0.61, 0.43, 0.493, resp.) revealed the better performance of 24-hour urinary aldosterone. CONCLUSIONS: In conclusion, 24-hour urinary aldosterone level performed better to predict the presence of LVH and inappropriate LVMI in patients with PA.

Urinary corticosteroid excretion predicts left ventricular mass and proteinuria in chronic kidney disease.

Blockade of the MR (mineralocorticoid receptor) in CKD (chronic kidney disease) reduces LVMI [LV (left ventricular) mass index] and proteinuria. The MR can be activated by aldosterone, cortisol and DOC (deoxycorticosterone). The aim of the present study was to explore the influence of mineralocorticoids on LVMI and proteinuria in patients with CKD. A total of 70 patients with CKD and 30 patients with EH (essential hypertension) were recruited. Patients underwent clinical phenotyping; biochemical assessment and 24 h urinary collection for THAldo (tetrahydroaldosterone), THDOC (tetrahydrodeoxycorticosterone), cortisol metabolites (measured using GC-MS), and urinary electrolytes and protein [QP (proteinuira quantification)]. LVMI was measured using CMRI (cardiac magnetic resonance imaging). Factors that correlated significantly with LVMI and proteinuria were entered into linear regression models. In patients with CKD, significant predictors of LVMI were male gender, SBP (systolic blood pressure), QP, and THAldo and THDOC excretion. Significant independent predictors on multivariate analysis were THDOC excretion, SBP and male gender. In EH, no association was seen between THAldo or THDOC and LVMI; plasma aldosterone concentration was the only significant independent predictor. Significant univariate determinants of proteinuria in patients with CKD were THAldo, THDOC, USod (urinary sodium) and SBP. Only THAldo excretion and SBP were significant multivariate determinants. Using CMRI to determine LVMI we have demonstrated that THDOC is a novel independent predictor of LVMI in patients with CKD, differing from patients with EH. Twenty-four hour THAldo excretion is an independent determinant of proteinuria in patients with CKD. These findings emphasize the importance of MR activation in the pathogenesis of the adverse clinical phenotype in CKD.

Impact of cardiovascular risk factors and inflammatory status on urinary 8-OHdG in essential hypertension.

BACKGROUND: The urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect the oxidation status of hypertensive subjects and it can be used for monitoring oxidative stress changes. However, the influence of cardiovascular risk factors and inflammation on the urinary levels of this marker in hypertension (HT) has never evaluated. The purpose of this study was to analyze the impact of cardiovascular risk factors, and established inflammatory markers on 8-OHdG in essential HT. METHODS: We studied 149 asymptomatic hypertensive patients (61 ± 14 years). A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Urinary 8-OHdG and plasma tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and interleukin-6 (IL-6) were determined. RESULTS: 8-OHdG/creatinine levels were higher in hypertrophic patients (P = 0.022) and correlated with left ventricular mass index (P < 0.01). When 8-OHdG/creatinine was compared according to obesity and diabetes in our hypertensive subjects, no significant differences were found. 8-OHdG/creatinine was increased in hypertensive smokers (P = 0.032) and women (P = 0.006). Furthermore, 8-OHdG/creatinine correlated with TNF-α, sTNF-R1, sTNF-R2 (P < 0.0001), and with IL-6 (P < 0.05). A multivariate linear regression analysis showed that gender, smoking, and TNF-α were independent factors of 8-OHdG/creatinine. CONCLUSIONS: Urinary 8-OHdG was increased in hypertensive patients with hypertrophy even under medical treatment. The presence of other cardiovascular risk factors on top of HT do not alter the concentrations of this oxidative stress marker, only smoking increasing its levels. TNF-α is an independent factor of 8-OHdG. These data suggest that this urinary marker gives specific additional information, further than blood pressure control alone, when evaluating hypertensive patients.

Association of sodium and potassium intake with left ventricular mass: coronary artery risk development in young adults.

High salt intake may affect left ventricular mass (LVM). We hypothesized that urinary sodium (UNa) and sodium/potassium ratio (UNa/K) are associated with LVM in a predominantly normotensive cohort of young adults. The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a multicenter cohort of black and white men and women aged 30±3.6 years at the time of baseline echocardiographic examination (1990-1991). 2D guided M-mode LVM indexed to body size (grams per meter(2.7)) was calculated, and UNa and potassium excretion assessed (average of three 24-hour urinary samples, n=1042). Linear and logistic regression analysis was used. Participants were 57% women and 55% black. Only 4% were hypertensive. UNa, urinary potassium, and UNa/K ratios were (mean±SD) 175.6±131.0, 56.4±46.3, and 3.4±1.4 mmol/24 h, respectively. Participants in the highest versus the lowest UNa excretion quartile had the greatest LVM (37.5 versus 34.0 g/m(2.7); P<0.001). Adjusted for age, sex, education, and race, LVM averaged 0.945 g/m(2.7) higher per SD of UNa/K (P=0.001). The relationship between UNa/K and LVM persisted among 399 participants with repeat echocardiographic measures 5 years later. In logistic regression analysis adjusted for age, sex, education, and race, each SD higher baseline UNa/K was associated with 23% and 38% greater chances of being in the highest quartile of LVM at baseline (odds ratio: 1.23; P=0.005) and 5 years later (odds ratio: 1.38; P=0.02). A higher sodium/potassium excretion ratio is significantly related to cardiac structure, even among healthy young adults.

Microalbuminuria and left ventricular mass in overweight and obese hypertensive patients: role of the metabolic syndrome.

BACKGROUND: Left ventricular hypertrophy (LVH) and microalbuminuria are common in hypertensive patients and are often associated with metabolic syndrome (MetS). However, it is not clear whether MetS could modify the association between cardiac and renal damage. OBJECTIVE: The aim of this study was to assess if the relationship of albumin/creatinine ratio (ACR) and left ventricular mass (LVM) could be independent from MetS in hypertensive overweight/obese patients. METHODS: 180 essential hypertensive and overweight/obese (body mass index [BMI] ≥25 kg/m(2)) patients referred to our Hypertension Centre from January 2006 to April 2009 because of blood pressure (BP) control-related problems were studied. Exclusion criteria were scarce adherence to antihypertensive drug therapy as investigated by the Morisky Medical Adherence Scale (MMAS), heart failure (New York Heart Association III or IV or left ventricular ejection fraction [LVEF] <50%), liver failure, cancer or other systemic severe diseases. MetS was defined according to the National Cholesterol Education Program (USA) Adult Treatment Panel III classification as modified by the American Heart Association. ACR was obtained from first morning urine specimens. Left ventricular dimensions, mass and ejection fraction, were measured by echocardiography following the American Society of Echocardiography recommendations. RESULTS: Patients with microalbuminuria had a 6-fold higher risk for LVH/h(2.7) and 2-fold higher risk for LVH/body surface area (BSA). Univariate linear regression analysis showed a positive relationship between ACR and LVM, expressed both as LVM/h(2.7) or LVM/BSA, as well as a direct correlation between logACR and interventricular diameters and ejection fraction. Regression models including logACR, estimated glomerular filtration rate, BMI, age, hypertension duration, smoking and MetS (as a single variable as well as each single component), showed that only logACR, BMI, hypertension duration and systolic blood pressure (SBP) were independently associated with LVM/h(2.7). CONCLUSION: Along with BP and BMI, albuminuria measured in a morning urine sample as ACR is a valuable low-cost index of cardiac organ damage and increased cardiovascular risk in hypertensive patients independently by MetS. On the other hand, MetS is not an independent risk factor for cardiac damage because it does not seem to add anything more than the sum of each of its components (especially SBP and adiposity indexed by BMI) to the relationship between cardiac and renal subclinical organ damage.