Objectives This study sought to assess sex differences in ventricular-arterial interactions. Background Heart failure with preserved ejection fraction is more prevalent in women than in men, but the ...basis for this difference remains unclear. Methods Echocardiography and arterial tonometry were performed to quantify arterial and ventricular stiffening and interaction in 461 participants without heart failure (189 men, age 67 ± 9 years; 272 women, age 65 ± 10 years). Aortic characteristic impedance (Zc ), total arterial compliance (pulsatile load), and systemic vascular resistance index (steady load) were compared between men and women, and sex-specific multivariable regression analyses were performed to assess associations of these arterial parameters with diastolic dysfunction and ventricular-arterial coupling (effective arterial elastance/left ventricular end-systolic elastance Ea/Ees) after adjustment for potential confounders. Results Zc was higher and total arterial compliance was lower in women, whereas systemic vascular resistance index was similar between sexes. In women but not men, higher log Zc was associated with mitral inflow E/A ratio (β ± SE: −0.17 ± 0.07), diastolic dysfunction (odds ratio: 7.8; 95% confidence interval: 2.0 to 30.2) and Ea/Ees (β ± SE: 0.13 ± 0.04) (p ≤ 0.01 for all). Similarly, total arterial compliance was associated with E/A ratio (β ± SE: 0.12 ± 0.04), diastolic dysfunction (odds ratio: 0.33; 95% confidence interval: 0.12 to 0.89), and Ea/Ees (β ± SE: −0.09 ± 0.03) in women only (p ≤ 0.03 for all). Systemic vascular resistance index was not associated with diastolic dysfunction or Ea/Ees. Conclusions Proximal aortic stiffness (Zc ) is greater in women than men, and women may be more susceptible to the deleterious effects of greater pulsatile and early arterial load on diastolic function and ventricular-arterial interaction. This may contribute to the greater risk of heart failure with preserved ejection fraction in women.
Urinary podocyte excretion as a marker for preeclampsia Garovic, Vesna D., MD; Wagner, Steven J., MD; Turner, Stephen T., MD ...
American journal of obstetrics and gynecology,
04/2007, Letnik:
196, Številka:
4
Journal Article
Recenzirano
Objective The objective of this study was to examine whether podocyturia, which is the urinary excretion of viable podocytes (glomerular epithelial cells), is present in urinary sediments of patients ...with preeclampsia. We also aimed to compare the test characteristics of podocyturia to those angiogenic factors that have been shown to play an important role in the pathogenesis of preeclampsia (s-Flt-1, PlGF, and endoglin). Study Design Serum angiogenic factors were measured in 44 patients with preeclampsia and 23 normotensive control patients. In a patient subset (15 cases and 16 control patients), urinary proteinuria were identified and quantified on the basis of their expressions of podocyte-specific proteins. Results Urinary podocyte excretion occurred in all patients with preeclampsia. The positive predictive value for the diagnosis of preeclampsia was greater for podocyturia than for any of the measured angiogenic factors. Conclusion Podocyturia is a highly sensitive and specific marker for preeclampsia. It may contribute to the development of proteinuria in preeclampsia.
Objectives Our goal was to evaluate the associations of central arterial stiffness, measured by aortic pulse wave velocity (aPWV), with subclinical target organ damage in the coronary, peripheral ...arterial, cerebral, and renal arterial beds. Background Arterial stiffness is associated with adverse cardiovascular outcomes. We hypothesized that aPWV is associated with subclinical measures of atherosclerosis—coronary artery calcification (CAC) and ankle-brachial index (ABI) and arteriolosclerosis—brain white matter hyperintensity (WMH) and urine albumin-creatinine ratio (UACR). Methods Participants (n = 812; mean age 58 years; 58% women, 71% hypertensive) belonged to hypertensive sibships and had no history of myocardial infarction or stroke. aPWV was measured by applanation tonometry, CAC by electron beam computed tomography, ABI using a standard protocol, WMH volume by brain magnetic resonance, and UACR by standard methods. WMH was log-transformed, whereas CAC and UACR were log-transformed after adding 1 to reduce skewness. The associations of aPWV with CAC, ABI, WMH, and UACR were assessed by multivariable linear regression using generalized estimating equations to account for the presence of sibships. Covariates included in the models were age, sex, body mass index, history of smoking, hypertension and diabetes, total and high-density lipoprotein cholesterol, estimated glomerular filtration rate, use of aspirin and statins, and pulse pressure. Results The mean ± SD aPWV was 9.8 ± 2.8 m/s. After adjustment for age, sex, conventional cardiovascular risk factors, and pulse pressure, higher aPWV (1 m/s increase) was significantly associated with higher log (CAC + 1) (β ± SE = 0.14 ± 0.04; p = 0.0003), lower ABI (β ± SE = −0.005 ± 0.002; p = 0.02), and greater log (WMH) (β ± SE = 0.03 ± 0.009; p = 0.002), but not with log (UACR + 1) (p = 0.66). Conclusions Higher aPWV was independently associated with greater burden of subclinical disease in coronary, lower extremity, and cerebral arterial beds, highlighting target organ damage as a potential mechanism underlying the association of arterial stiffness with adverse cardiovascular outcomes.
Background Selection of antihypertensive therapy is often empiric, and use of genetic information to guide drug therapy selection holds future promise. Trial design The objective of this trial is to ...identify the genetic determinants of the antihypertensive and adverse metabolic responses to a thiazide diuretic (hydrochlorothiazide), a β-blocker (atenolol), and their combination. This will be accomplished through candidate gene and genome-wide association approaches. Individuals with uncomplicated hypertension (N = 800), with ages 17 and 65 years, are being enrolled. Current antihypertensive therapy is discontinued, and hypertension is confirmed, along with collection of other baseline data. Subjects are then randomized to either hydrochlorothiazide or atenolol, with 1 dose titration step, followed by assessment of response to therapy after at least 6 weeks on the target dose. Those with blood pressure >120/70 mm Hg have the second drug added, with similar dose titration and response assessment procedures. Data collected include home, office, and 24-hour ambulatory blood pressure. Biological samples collected in the fasting state include plasma, serum, DNA (buffy coat), and urine. Epstein-Barr virus transformed lymphocyte cell lines are also being created. Conclusions Pharmacogenetic-guided therapy holds clinical potential for hypertension, but the literature in the field is limited. This trial will add substantially to our understanding of the genetic determinants of antihypertensive and adverse metabolic responses to 2 commonly used antihypertensive drug classes.
Background Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. Study Design We conducted 2 targeted analyses. First, we ...examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10−4 (0.05/325 tests). Setting & Participants Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium. Predictor We used 19 kidney SNPs and 64 vascular SNPs. Outcomes & Measurements Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. Results In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic ( P = 9.3 ×10−10 ) and diastolic ( P = 1.6 ×10−14 ) blood pressure and coronary artery disease ( P = 2.2 ×10−6 ), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus ( P = 1.06 ×10−07 and P = 7.05 ×10−08 ). Limitations The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. Conclusions Overall, although we confirmed one locus ( SH2B 3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.
The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary ...excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined.
Genome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume).
One region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near TRPM6, whose protein product mediates magnesium transport in the colon and kidney, and C9orf40, C9orf41, NMRK1, and OSTF1 (rs1176815; P=1.70×10–14, with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; P=1.12×10–8) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs.
Common variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion.
To determine whether women who had a hypertensive pregnancy disorder (HPD) have elevated uric acid concentrations decades after pregnancy as compared with women who had normotensive pregnancies.
The ...Genetic Epidemiology Network of Arteriopathy study measured uric acid concentrations in Hispanic (30%), non-Hispanic white (28%), and non-Hispanic black (42%) women (mean age, 60 ± 10 years). This cross-sectional study was conducted between July 1, 2000, and December 31, 2004. Hispanic participants were recruited from families with high rates of diabetes, whereas non-Hispanic participants were recruited from families with high rates of hypertension. This analysis compared uric acid concentrations in women with a history of normotensive (n = 1846) or hypertensive (n = 408) pregnancies by logistic regression.
Women who had an HPD had higher uric acid concentrations (median, 5.7 mg/dL vs 5.3 mg/dL; P < .001) and were more likely to have uric acid concentrations above 5.5 mg/dL (54.4% vs 42.4%; P = .001) than were women who had normotensive pregnancies. These differences persisted after adjusting for traditional cardiovascular risk factors, comorbidities, and other factors that affect uric acid concentrations. A family-based subgroup analysis comparing uric acid concentrations in women who had an HPD (n = 308) and their parous sisters who had normotensive pregnancies (n = 250) gave similar results (median uric acid concentrations, 5.7 mg/dL vs 5.2 mg/dL, P = 0.02; proportion of women with uric acid concentrations > 5.5 mg/dL, 54.0% vs 40.3%, P < .001).
Decades after pregnancy, women who had an HPD have higher uric acid concentrations. This effect does not appear to be explained by a familial predisposition to elevated uric acid concentrations.
Objective This study was undertaken to validate a self-administered questionnaire in verifying the diagnosis of preeclampsia, eclampsia, or toxemia in a group of women with a greater than 20-year ...history of preeclampsia. Study Design Questionnaires were mailed to a random sample of 144 women who received a diagnosis of any of these 3 conditions and 158 women who had normotensive pregnancies at Mayo Clinic, Rochester, Minnesota, from 1960-1979. Results A previous diagnosis of preeclampsia, eclampsia, or toxemia was verified with 80% sensitivity and 96% specificity. Conclusion Our validated questionnaire may be a useful research tool in identifying women with a previous history of preeclampsia. Women with a history of preeclampsia had a higher prevalence of future hypertension than those with a history of normotensive pregnancy.
To evaluate cardiac troponin T (cTnT) as a predictor of end-stage renal disease (ESRD) and death in a cohort of African American and white community-dwelling adults with hypertensive families.
A ...total of 3050 participants (whites from Rochester, Minnesota; African Americans from Jackson, Mississippi) of the Genetic Epidemiology Network of Arteriopathy study were followed from baseline examination (June 1, 1996, through August 31, 2000) through January 22, 2010. Cox proportional hazards regression models were used to examine the association of cTnT with ESRD and death after adjusting for traditional risk factors.
Cohort demographic characteristics and measurements included 1395 whites (45.7%), 2174 hypertensive (71.3%), 992 estimated glomerular filtration rate of less than 60 mL/min per 1.73 m(2) (32.5%), 1574 high-sensitivity C-reactive protein level of greater than 3 mg/L (51.6%), and 66 abnormal cTnT level of 0.01 ng/mL or higher (2.2%). The estimated cumulative incidence of ESRD at 10 years was 27.4% among those with abnormal cTnT levels compared with 1.3% for those with normal levels. Similarly, the estimated cumulative incidence of death at 10 years was 47% among those with abnormal cTnT compared with 7.3% among those with normal cTnT. Abnormal cTnT levels were strongly associated with ESRD and death. This effect was attenuated but was still highly significant after adjustment for demographic characteristics, estimated glomerular filtration rate, and traditional risk factors for ESRD (unadjusted hazard ratio HR, 23.91; 95% CI, 12.9-44.2; adjusted HR, 2.81; 95% CI, 1.3-5.9) and death (unadjusted HR, 8.43; 95% CI, 6.0-11.9; adjusted HR, 3.46; 95% CI, 2.3-5.1).
Cardiac troponin T makes an independent contribution to the prediction of ESRD and all-cause death in community-dwelling individuals beyond traditional risk markers. Further studies may be needed to determine whether cTnT screening in individuals with hypertension or in a subset of hypertensive individuals would help identify those at risk of ESRD and all-cause death.
Arterial stiffness is associated with incident hypertension. We hypothesized that measures of arterial stiffness would predict increases in systolic (SBP), mean (MAP), and pulse pressure (PP) over ...time in treated hypertensives. Blood pressure (BP) was measured a mean of 8.5 ± 0.9 years apart in 414 non-Hispanic white hypertensives (mean age, 60 ± 8 years; 55% women). The average of three supine right brachial BPs was recorded. Measures of arterial stiffness, including carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), and central pulse pressure (CPP), were obtained at baseline by applanation tonometry. We performed stepwise multivariable linear regression analyses adjusting for potential confounders to assess the associations of arterial stiffness parameters with BP changes over time. SBP, MAP, and PP increased in 80% of participants. After adjustment for covariates listed, cfPWV (m/s) was associated with increases in SBP (β ± standard error SE, 0.71 ± 0.31) and PP (β ± SE, 1.09 ± 0.27); AIx (%) was associated with increases in SBP (β ± SE, 0.23 ± 0.10) and MAP (β ± SE, 0.27 ± 0.07); and CPP (mmHg) was associated with increases in SBP (β ± SE, 0.44 ± 0.07), MAP (β ± SE, 0.24 ± 0.05), and PP (β ± SE, 0.42 ± 0.06) over time (P ≤ .02 for each). In conclusion, arterial stiffness measures were associated with longitudinal increases in SBP, MAP, and PP in treated hypertensives.
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