Obesity Cut-Off Points Using Prepregnancy Body Mass Index according to Cardiometabolic Conditions in Pregnancy.

Aim: To suggest cut-off points for body mass index (BMI) using gestational hypertension, preeclampsia, and gestational diabetes mellitus (GDM) as cardiometabolic conditions in pregnancy. Methods: In this prospective study, singleton pregnant women from the fetal medicine service of the Brazilian Unified Health System were included. The pregnancy, perinatal, and newborn data were obtained from the clinical medical records. Maternal anthropometry included an assessment of weight and height and the prepregnancy BMI evaluation categorized according to the World Health Organization cut-off points. The area under the curve and confidence interval values from receiver operator curves were generated to identify the optimal cut-off points using prepregnancy BMI with better sensitivity and specificity. Results: Data on 218 pregnancies were analyzed, with 57.9% (n = 124) being classified as overweight/obese, 11% (n = 24) with GDM, 6.9% (n = 15) with preeclampsia, and 11.0% (n = 24) with gestational hypertension. The BMI cut-off points for predicting cardiometabolic conditions were 27.52 kg/m2 (S: 66.7%; E: 63.8%) for women with GDM; 27.40 kg/m2 (S: 73.3%; E: 62.4%; S: 79.2%; E: 64.9%; S: 70.3%; E: 66.3%) for women with preeclampsia, gestational hypertension, and gestational hypertension plus preeclampsia, respectively; and 27.96 kg/m2 (S: 69.6%; E: 65.6%) for women with preeclampsia plus GDM. Conclusion: The findings suggest that the optimal prepregnancy BMI cut-off point is around 27 kg/m2 for pregnant women with maternal cardiometabolic conditions.

Relationship Between Circulating MicroRNAs and Left Ventricular Hypertrophy in Hypertensive Patients.

Objective: Left ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients. Methods: Two cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively. Results: Among the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus. Conclusions: Our data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.

Measurement of sulfatides in the amniotic fluid supernatant: A useful tool in the prenatal diagnosis of metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by deficiency of arylsulfatase A (ARSA), leading to an accumulation of sulfatides. Sulfatides have been quantified in urine, dried blood spots (DBS), and tissues of patients with MLD. Newborn screening (NBS) for MLD has already been proposed based on a two-tier approach with the quantification of sulfatides in DBS followed by the quantification of ARSA by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Prenatal screening for MLD is also crucial, and sulfatide quantification in amniotic fluid (AF) can aid diagnosis. The prenatal study was initiated due to a family history of MLD at 19 weeks of gestation. ARSA was quantified in cultured amniocytes. C16:0 sulfatide was quantified by LC-MS/MS in the supernatant of AF. Molecular analysis of the ARSA gene was performed in cultured amniocytes. ARSA was deficient in fetal cells, and C16:0 sulfatides were significantly elevated in comparison to age-matched controls (3-fold higher). Genetic studies identified the c.465+1G>A variant in homozygosis in the ARSA gene. Our study shows that sulfatides can be quantified in the supernatant of AF of MLD fetuses, and it could potentially aid in a faster and more accurate diagnosis of MLD patients.

Association of carotid wall layers with atherosclerotic plaques and cardiac hypertrophy in hypertensive subjects.

Carotid intima-media thickness (cIMT) is considered a marker of subclinical atherosclerosis and is related to target-organ damage in hypertensive patients. However, increased cIMT may be due to increases in the thickness of intima (cIT) and media (cMT) layers. This study evaluated whether cIMT layers (cIT and cMT) had a greater association with carotid atherosclerotic plaques and left ventricular hypertrophy (LVH) than cIMT in hypertensive subjects. We cross-sectionally evaluated clinical, carotid, and echocardiography characteristics of 186 hypertensive patients followed at an outpatient clinic. High-resolution images of common carotid arteries were obtained by ultrasonography equipped with 10-MHz transducers, and cIT, cMT, and cIMT were manually measured using an image-processing software. Among all participants (n = 186; age = 60.8 ± 10.9 years, 43% males), there were 58% with carotid plaques and 58% with LVH. Mean cIT, cMT, and cIMT values were 0.267 ± 0.060, 0.475 ± 0.107, and 0.742 ± 0.142 mm, respectively. In logistic regression analysis adjusted for relevant covariates, carotid plaques showed stronger association with cIT than with cMT and cIMT. Furthermore, cIT showed greater area under the ROC curve (0.92; 95% CI 0.87-0.96) than cIMT (0.79; 95% CI 0.72-0.85) and cMT (0.64; 95% CI 0.56-0.72) to identify plaques. Conversely, cIT, cMT, and cIMT had modest association and accuracy to identify LVH (area under the ROC curve = 0.61, 0.57, and 0.60, respectively). In conclusion, cIT is a more accurate marker of atherosclerosis than cMT or cIMT, while cIT and cMT provide no incremental value in identifying LVH when compared with cIMT among hypertensive subjects.

Association of Circulating miR-145-5p and miR-let7c and Atherosclerotic Plaques in Hypertensive Patients.

AIM: Hypertension is a strong risk factor for atherosclerosis. Increased carotid intima-media thickness (cIMT) and carotid plaques are considered subclinical markers of atherosclerosis. This study aimed at evaluating the serum expression of miRNAs previously related to adverse vascular remodeling and correlating them with carotid plaques and cIMT in hypertensive patients. METHODS: We cross-sectionally evaluated the clinical and carotid characteristics as well as serum expression of miR-145-5p, miR-let7c, miR-92a, miR-30a and miR-451 in 177 hypertensive patients. Carotid plaques and cIMT were evaluated by ultrasound, and the expression of selected miRNAs was evaluated by a quantitative polymerase chain reaction. RESULTS: Among all participants (age = 60.6 ± 10.7 years, 43% males), there were 59% with carotid plaques. We observed an increased expression of miR-145-5p (Fold Change = 2.0, p = 0.035) and miR-let7c (Fold Change = 3.8, p = 0.045) in participants with atherosclerotic plaque when compared to those without plaque. In the logistic regression analysis adjusted for relevant covariates, these miRNAs showed a stronger association with carotid plaques (miR-145-5p: Beta ± SE = 0.050 ± 0.020, p = 0.016 and miR-let7c: Beta ± SE = 0.056 ± 0.019, p = 0.003). CONCLUSIONS: Hypertensive patients with carotid plaques have an increased expression of miR-145-5p and miR-let7c, suggesting a potential role of these miRNAs as a biomarker for subclinical atherosclerosis in hypertensive individuals.

Hipertrofia cardíaca associada à hipertensão arterial com disfunção sistólica subclínica: relato de caso / Cardiac hypertrophy associated with arterial hypertension with subclinical systolic sysfunction: a case report

Relata-se um caso de uma paciente de 66 anos, com diagnóstico de hipertensão arterial sistêmica há seis anos, obesa e tabagista, que compareceu à consulta para avaliação cardiológica pré-operatória de cirurgia ginecológica. Ao exame clínico, apresentava-se com pressão arterial de 132 x 80mmHg, pulsos radiais e femorais simétricos, auscultas cardíaca e respiratória normais. O eletrocardiograma mostrou ritmo sinusal, sem alterações, enquanto o ecocardiograma transtorácico revelou hipertrofia concêntrica do ventrículo esquerdo, câmaras cardíacas com dimensões normais e fração de ejeção do ventrículo esquerdo preservada. A avaliação do strain longitudinal global demonstrou diminuição da deformação miocárdica sistólica. Neste relato, ilustramos um caso clínico de hipertrofia ventricular esquerda associada à hipertensão arterial, com fração de ejeção do ventrículo esquerdo preservada e disfunção sistólica subclínica diagnosticada pelo strain miocárdico.

We report a case of a 66-year-old obese and smoker woman, with a 6-year diagnosis of systemic hypertension, who searched medical assistance for pre-operative cardiology evaluation. The clinical examination revealed blood pressure of 132x80mmHg, symmetrical radial and femoral pulses, and normal cardiac and lung auscultation. The electrocardiogram showed sinus rhythm with no alterations, while an echocardiogram showed concentric left ventricular hypertrophy, normal cardiac chambers dimensions and normal left ventricular ejection fraction. Left ventricular global longitudinal strain evaluation revealed reductions in systolic myocardial deformation. In this case, we discuss the presence of left ventricular hypertrophy secondary to hypertension, with preserved left ventricular ejection fraction and subclinical systolic dysfunction detected with myocardial strain.

Saturated Fat Intake Is Related to Heart Rate Variability in Women with Polycystic Ovary Syndrome.

BACKGROUND/AIMS: There is a heightened risk for cardiovascular diseases in women with polycystic ovary syndrome (PCOS). Alterations in heart rate variability (HRV) may reflect subclinical cardiovascular disease, with a putative association between HRV and dietary fat. This study evaluated HRV in PCOS and control women based on the dietary intake of saturated fatty acid (SFA). METHODS: Biochemical/hormonal profile, resting metabolic rate, physical activity, HRV in response to the Stroop test, and dietary intake were assessed in 84 PCOS and 54 control women stratified by median SFA intake in the PCOS group (8.5% of daily energy intake). RESULTS: Body mass index (p = 0.041), blood pressure (p < 0.01), and HOMA-IR (p = 0.003) were higher in PCOS vs. CONTROLS: PCOS women had higher testosterone (p = 0.001), dehydroepiandrosterone sulfate (p = 0.012), and free androgen index (p = 0.001), and lower sex hormone-binding globulin levels than controls (p = 0.001). In both groups, the clinical profile and calorie intake were similar between SFA categories. In PCOS, testosterone was lower when SFA intake <8.5%. PCOS women with SFA <8.5% consumed more beans, fruits, and vegetables and had better frequency and time domain HRV indices. No differences in HRV were detected between SFA categories in controls. In PCOS, age and SFA intake were independent predictors of HRV. CONCLUSIONS: Lower SFA intake is related to improved cardiovascular autonomic function in PCOS.

Carotid flow velocity/diameter ratio is a predictor of cardiovascular events in hypertensive patients.

OBJECTIVE: The aim of this study was to evaluate the performance of common carotid artery diameter, flow velocity and flow velocity/artery diameter ratio as predictors of major adverse cardiovascular events (MACEs) in a sample of hypertensive patients. METHODS: A cohort of 403 hypertensive patients was followed up for a median of 1260 (714) days, and 27 suffered MACEs. At baseline, participants were evaluated by clinical, laboratory, echocardiographic and carotid ultrasound analysis. RESULTS: Patients with peak-systolic flow velocity (sFV) less than the median value and systolic artery diameter (sAD) greater than the median value presented the worst clinical outcome compared to those with isolated sFV less than the median value or sAD greater than the median value, suggesting an additive effect of these two variables. Further, Kaplan-Meier analysis demonstrated worse outcome for individuals with sFV/sAD ratio less than 85.7/s (optimal cut-off point obtained by receiver-operating characteristic analysis) compared to those with higher sFV/sAD values (log-rank test: P < 0.0001). In stepwise multivariable Cox-regression analyses, sFV/sAD was significantly associated with MACEs (P < 0.001), whereas carotid intima-media thickness and clinically defined high cardiovascular risk did not. Furthermore, area under the receiver-operating characteristic curve for sFV/sAD was higher than that for Framingham risk score (0.77 versus 0.64; P = 0.045), whereas adding sFV/sAD to the Framingham risk factors resulted in increased net reclassification improvement (P = 0.041) and integrated discrimination improvement (P < 0.001). CONCLUSIONS: Lower carotid sFV/sAD was associated with MACEs in hypertensive patients independent of cardiovascular prediction models and carotid intima-media thickness. These findings suggest that this index may be a promising approach to identify hypertensive subjects at increased risk for future cardiovascular events.

Onset of hypertension during pregnancy is associated with long-term worse blood pressure control and adverse cardiac remodeling.

Up to 20% of women with hypertensive pregnancy disorders might persist with chronic hypertension. This study compared clinical and echocardiographic features between women whose hypertension began as hypertensive pregnancy disorders (PH group) and women whose diagnosis of hypertension did not occur during pregnancy (NPH group). Fifty PH and 100 NPH women were cross-sectionally evaluated by clinical, laboratory, and echocardiography analysis, and the groups were matched by duration of hypertension. PH exhibited lower age (46.6 ± 1.4 vs. 65.3 ± 1.1 years; P < .001), but higher systolic (159.8 ± 3.9 vs. 148.0 ± 2.5 mm Hg; P = .009) and diastolic (97.1 ± 2.4 vs. 80.9 ± 1.3 mm Hg; P < .001) blood pressure than NPH, although used more antihypertensive classes (3.4 ± 0.2 vs. 2.6 ± 0.1; P < .001). Furthermore, PH showed higher left ventricular wall thickness and increased prevalence of concentric hypertrophy than NPH after adjusting for age and blood pressure. In conclusion, this study showed that PH may exhibit worse blood pressure control and adverse left ventricular remodeling compared with NPH.

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients.

BACKGROUND: Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects. METHODS: We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitória (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample. RESULTS: Genotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height2.7 than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m2.7; p = 0.009), and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m2.7; p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03). CONCLUSIONS: The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height 2.7 and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

Sex-specific hemodynamic and non-hemodynamic determinants of aortic root size in hypertensive subjects with left ventricular hypertrophy.

Aortic root (AoR) dilatation is more frequently observed in hypertensive individuals and is independently associated with left ventricular (LV) hypertrophy. Although the LV structure has sex-specific predictors, it remains unknown whether there are gender-related differences in the determinants of AoR size. We carried out a cross-sectional analysis of clinical, laboratory, anthropometric, funduscopic and echocardiographic features of 438 hypertensive patients with LV hypertrophy (266 women and 172 men). Women with enlarged AoR had higher cardiac output (P=0.0004), decreased peripheral vascular resistance (P=0.009), higher prevalence of mild aortic regurgitation (P=0.02) and increased waist circumference (P=0.04), whereas AoR-dilated men presented with a higher prevalence of concentric LV hypertrophy (P=0.0008) and mild aortic regurgitation (P=0.005) and increased log C-reactive protein levels (P=0.02), compared with sex-matched normal AoR subjects. In women, AoR dilatation associated with cardiac output, mild aortic regurgitation and waist circumference in a multivariate model including age, body surface area, height, homeostasis model assessment index, LV mass index, diastolic blood pressure, menopause status and use of antihypertensive medications as independent variables. Conversely, AoR dilatation associated with LV relative wall thickness, log C-reactive protein and mild aortic regurgitation without contributions from diastolic blood pressure, height, body surface area, LV mass index, peripheral vascular resistance and antihypertensive medications in men. Taken together, these results suggest that both volume overload and abdominal obesity are related to AoR dilatation in hypertensive women, whereas AoR enlargement is associated more with inflammatory and myocardial growth-related parameters in hypertensive men with LV hypertrophy.

Prenatal diagnosis of fetal chromosomal abnormalities: report of an 18-year experience in a Brazilian public hospital

The study of the fetal karyotype became an important tool for the fetal diagnosis of genetic diseases in the 1970s. Although application of this test has remained very restricted in Brazil, we had 905 referrals for prenatal fetal karyotyping between 1989 and 2007. In 879 cases, a fetal karyotype was obtained. We detected 74 abnormal karyotypes (8.4%), the majority being found when the prior indication was fetal malformation. When obtaining amniotic fluid or chorionic villus samples was difficult, alternative fetal materials (urine, cystic hygroma, cystic lung, intreperitoneal and cerebrospinal fluids) were collected and we had success in obtaining karyotypes in all 13 cases. Although, the option of terminating abnormal pregnancies does not legally exist in Brazil, the information gained in assessing the prognosis of on-going pregnancies or estimating recurrence risks justifies prenatal diagnosis of chromosome abnormalities. We conclude that, in keeping with the policy in most other countries, prenatal cytogenetic analysis is strongly recommended in high-risk pregnancies for fetal abnormalities. However, the unique aspect of this type of study is not its rarity in world terms, but its rarity in Brazil. This argues that Brazilian health policy on prenatal diagnosis requires reforming to make it much more widely available within the public health care sector.

Upper arm circumference is an independent predictor of left ventricular concentric hypertrophy in hypertensive women.

Upper arm circumference (UAC) measurement is necessary for the proper sizing of cuffs and is recommended for accurate blood pressure (BP) assessment. The aim of this report is to identify and quantify the relationships between UAC and the usual anthropometric measurements of body fat distribution and cardiac structure in hypertensive subjects. We evaluated 339 patients (202 women and 137 men) by medical history, physical examination, anthropometry, metabolic and inflammatory parameters, and echocardiography. Partial correlation analyses adjusted for age and body mass index revealed that anthropometric variables were significantly associated with echocardiographic parameters exclusively in women. In this regard, UAC correlated with interventricular septum thickness, posterior wall thickness, and relative wall thickness >or=0.45, while waist circumference was related to left cardiac chamber diameter. Multivariate analyses including age, body mass index, systolic BP, homeostasis model assessment index, and use of antihypertensive medications demonstrated that UAC was an independent predictor of left ventricular wall thickness and concentric hypertrophy in women. Further linear regression analyses revealed that waist circumference was an independent predictor of left ventricular end-diastolic and left atrial diameters in this gender. Overall, these findings suggest that UAC determination might serve not only as a routine approach preceding BP evaluation but also as a simple and feasible predictor of adverse LV remodeling in hypertensive women.

Investigation of lysosomal storage diseases in nonimmune hydrops fetalis.

OBJECTIVE: To investigate lysosomal storage diseases (LSD) in cases of nonimmune hydrops fetalis (NIHF). METHODS: Thirty-three cases of NIHF were investigated, 28 in the prenatal period and 5 in hydropic newborns. In addition to a general investigation for NIHF, specific enzymatic analyses for the detection of LSD were performed. RESULTS: In our sample, we detected five patients (15%) with LSD, each patient having one of the following diseases: mucolipidosis, Niemann-Pick disease, galactosialidosis, sialidosis and mucopolysaccharidosis type IV A. CONCLUSION: Although LSDs are rare disorders as a group, they should be considered as a possible cause of NIHF, even in the absence of consanguinity or of a previous family history. By excluding the more frequent causes of NIHF, an LSD investigation assists in clarifying the etiology of many hydropic cases, making more appropriate genetic counseling for parents possible.

Determinantres da mortalidade materna: analise de 17391 partos no Hospital de Clinicas de Porto Alegre / Determinant factors of maternal mortality: analysis of 17391 deliveries at the Hospital de Clinicas de Porto Alegre

Os autores estudaram 16 obitos maternos ocorridos no Hospital de Clinicas de Porto Alegre no periodo de 1 de janeiro de 1985 a 30 de junho de 1990. O numero total de partos ocorridos no referido periodo foi de 17391. O coeficiente de mortalidade materna foi de 34,50 (para cada 100.000 nascidos vivos e corrigido). Verificou-se que 10 casos vieram encaminhados de outros hospitais com complicacoes anteriores a baixa e 6 casos de internacao direta, sem transferencia. Em relacao as causas dos obitos tivemos: 10 (62,5 por cento), por infeccao; 3 (18,7 por cento) por doenca hipertensiva relacionada a gestacao; 2 (12,5 por cento) por hemorragia e 1 (6,3 por cento) por coriocarcinoma. Os obitos ocorreram por causas diretas e indiretas. O reconhecimento dos fatores determinantes do obituario materno e de suma importancia pois sabe-se que aproximadamente 70 por cento desses obitos sao evitaveis. A sua prevencao deve ser a meta dos servicos de assistencia obstetrica, sobretudo nos paises do terceiro mundo onde os indices de morbiletalidade materna ainda sao elevados