Hypertension and the roles of the 9p21.3 risk locus: Classic findings and new association data.

BACKGROUND: The band 9p21.3 contains an established genomic risk zone for cardiovascular disease (CVD). Since the initial 2007 Wellcome Trust Case Control Consortium study (WTCCC), the increased CVD risk associated with 9p21.3 has been confirmed by multiple studies in different continents. However, many years later there was still no confirmed report of a corresponding association of 9p21.3 with hypertension, a major CV risk factor, nor with blood pressure (BP). THEORY: In this contribution, we review the bipartite haplotype structure of the 9p21.3 risk locus: one block is devoid of protein-coding genes but contains the lead CVD risk SNPs, while the other block contains the first exon and regulatory DNA of the gene for the cell cycle inhibitor p15. We consider how findings from molecular biology offer possibilities of an involvement of p15 in hypertension etiology, with expression of the p15 gene modulated by genetic variation from within the 9p21.3 risk locus. RESULTS: We present original results from a Colombian study revealing moderate but persistent association signals for BP and hypertension within the classic 9p21.3 CVD risk locus. These SNPs are mostly confined to a 'hypertension island' that spans less than 60 kb and coincides with the p15 haplotype block. We find confirmation in data originating from much larger, recent European BP studies, albeit with opposite effect directions. CONCLUSION: Although more work will be needed to elucidate possible mechanisms, previous findings and new data prompt reconsidering the question of how variation in 9p21.3 might influence hypertension components of cardiovascular risk.

Fetal deaths in pregnancies with SARS-CoV-2 infection in Brazil: A case series.

BACKGROUND: There are few reports of miscarriages or stillbirths in women infected with SARS-CoV-2. We present five consecutive cases of fetal death (≥12 weeks) without other putative causes in women with laboratory-confirmed (RT-PCR) COVID-19 managed in a single Brazilian institution. CASE SERIES: All five women were outpatients with mild or moderate forms of COVID-19 and were not taking any medication. Four were nulliparous, all were overweight or obese, and none had any comorbidities or pregnancy complications that could contribute to fetal demise. Fetal death occurred at 21-38 weeks of gestation, on COVID-days 1-22. SARS-Cov-2 was detected by RT-PCR in amniotic fluid in one case and in placental specimens in two cases. All five women had acute chorioamnionitis on placental histology, massive deposition of fibrin, mixed intervillitis/villitis, and intense neutrophil and lymphocyte infiltration. One fetus had neutrophils inside alveolar spaces, suggestive of fetal infection. CONCLUSIONS: These five cases of fetal demise in women with confirmed COVID-19 without any other significant clinical or obstetric disorders suggest that fetal death can be an outcome of SARS-CoV-2 infection in pregnancy. The intense placental inflammatory reaction in all five cases raises the possibility of a direct effect of SARS-CoV-2 on the placenta.

Possible formation of pulmonary microthrombi in the early puerperium of pregnant women critically ill with COVID-19: Two case reports.

BACKGROUND: Limited data are available on the management of pregnant women with severe or critical forms of COVID-19, such as the optimal timing of provider-initiated delivery, and post-partum care, including antithrombotic prophylaxis. We present the clinical course, pre- and post-partum management, and outcomes of two pregnant women critically ill with COVID-19. CASES: Both women had confirmed SARS-CoV-2 pneumonia with rapid clinical decompensation that required admission to the intensive care unit, intubation, and delivery by emergency cesarean section at 32 and 29 weeks. Both patients clinically improved in the first two postoperative days, but this was followed by clinical, laboratory and radiological deterioration on the third postoperative day; however, they both improved again after full anticoagulation. This pattern suggests the possible formation of pulmonary microthrombi in the early puerperium. We discuss the challenges faced by the multiprofessional team in the management of these patients. CONCLUSIONS: There are few resources to guide health professionals caring for pregnant women with critical COVID-19. These two cases contribute to the rapidly evolving knowledge on the management and outcomes of pregnant women with COVID-19.

Dietary patterns and cardiometabolic risk factors among adolescents: systematic review and meta-analysis.

This study systematised and synthesised the results of observational studies that were aimed at supporting the association between dietary patterns and cardiometabolic risk (CMR) factors among adolescents. Relevant scientific articles were searched in PUBMED, EMBASE, SCIENCE DIRECT, LILACS, WEB OF SCIENCE and SCOPUS. Observational studies that included the measurement of any CMR factor in healthy adolescents and dietary patterns were included. The search strategy retained nineteen articles for qualitative analysis. Among retained articles, the effects of dietary pattern on the means of BMI (n 18), waist circumference (WC) (n 9), systolic blood pressure (n 7), diastolic blood pressure (n 6), blood glucose (n 5) and lipid profile (n 5) were examined. Systematised evidence showed that an unhealthy dietary pattern appears to be associated with poor mean values of CMR factors among adolescents. However, evidence of a protective effect of healthier dietary patterns in this group remains unclear. Considering the number of studies with available information, a meta-analysis of anthropometric measures showed that dietary patterns characterised by the highest intake of unhealthy foods resulted in a higher mean BMI (0·57 kg/m²; 95 % CI 0·51, 0·63) and WC (0·57 cm; 95 % CI 0·47, 0·67) compared with low intake of unhealthy foods. Controversially, patterns characterised by a low intake of healthy foods were associated with a lower mean BMI (-0·41 kg/m²; 95 % CI -0·46,-0·36) and WC (-0·43 cm; 95 % CI -0·52,-0·33). An unhealthy dietary pattern may influence markers of CMR among adolescents, but considering the small number and limitations of the studies included, further studies are warranted to strengthen the evidence of this relation.

Effect of increased calcium consumption from fat-free milk in an energy-restricted diet on the metabolic syndrome and cardiometabolic outcomes in adults with type 2 diabetes mellitus: a randomised cross-over clinical trial.

We investigated the effects of high-Ca fat-free milk phase (MD) (prescription of approximately 1500 mg of Ca/d) v. low-Ca phase (CD) (prescription of approximately 800 mg of Ca/d) in an energy-restricted diet on the metabolic syndrome (MetS) and cardiometabolic measures in individuals with type 2 diabetes mellitus (T2DM) and low habitual Ca consumption (<600 mg/d). In this randomised cross-over design, fourteen adults with T2DM (49·5 (sd 8·6) years, BMI 29·4 (sd 4·5) kg/m2) consumed either MD or CD for 12 weeks, with a washout of 18 weeks between phases. A breakfast shake containing 700 mg (MD) or 6·4 mg (CD) of Ca was consumed in the laboratory. In addition, energy-restricted diets were prescribed (800 mg of dietary Ca/d). Waist circumference (WC), fasting glucose, fasting TAG, systolic (SBP) and diastolic blood pressure (DBP), fasting total cholesterol, fasting LDL-cholesterol, fasting HDL-cholesterol, HDL:LDL ratio, HDL:TAG ratio and lipid accumulation product (LAP) index were assessed at baseline and after each phase. Ca consumption during the study was equivalent to 1200 mg/d during MD and 525 mg/d during CD. There was a greater reduction in WC, SBP, DBP and LAP index after MD compared with CD. HDL:LDL ratio increased and total cholesterol, LDL-cholesterol, SBP, DBP and LAP index decreased only in MD. The consumption of approximately 1200 mg of Ca/d (700 mg from fat-free milk+500mg from other dietary sources) associated with an energy-restricted diet decreased some of the MetS components and cardiometabolic measures in adults with T2DM.

Polymorphisms of the TNF-α gene interact with plasma fatty acids on inflammatory biomarker profile: a population-based, cross-sectional study in São Paulo, Brazil.

The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1ß (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population.

Metabolic syndrome's risk factors and its association with nutritional status in schoolchildren.

The metabolic risk factors (RF) to the diagnosis of metabolic syndrome (MetS) have been evidenced at early ages, including children. The aim of the present study was to identify the prevalence of RF to the diagnosis of MetS and its association with nutritional status of schoolchildren from 6 to 10 years old. A cross-sectional study was carried out in 505 students of municipal schools in Macae, Brazil, conducted from 2013 to 2014. The RF evaluated were: blood pressure (mm Hg), triglycerides (mmol/L), HDL-cholesterol (mmol/L) fasting glucose (mmol/L) and waist circumference (cm). At least one RF was present in 61% (n = 308) of the sample. By nutritional status, there was higher prevalence of RF in overweight/obese schoolchildren compared to those with normal weight, except in the concentration of HDL-c. The prevalence of one, two and three RF (MetS) were 34.7% (n = 175), 21.0% (n = 106) and 5.3% (n = 27), respectively. Two RF were more present in overweight (28.2% 95%CI 19.0; 39.0) and obese (41.5% 95%CI 31.4; 52.1) compared to normal weight children (13.5% 95%CI 9.9; 17.8). Three or more RF were more frequent among obese (25.5% 95%CI 17.0; 35.5) in relation to overweight (2.4% 95%CI 0.2; 8.2) and normal weight children (0.3% 95%CI 0; 1.7). The data indicate high prevalence of RF and its relationship with the magnitude of body weight excess. Therefore, the identification and early treatment of these RF might minimize the risk of MetS and related diseases.

No difference in acute effects of supplemental v. dietary calcium on blood pressure and microvascular function in obese women challenged with a high-fat meal: a cross-over randomised study.

Recent studies suggest that supplemental Ca (SC) increases the risk of cardiovascular events, whereas dietary Ca (DC) decreases the risk of cardiovascular events. Although frequently consumed with meals, it remains unclear whether Ca can mitigate or aggravate the deleterious effects of a high-fat meal on cardiovascular risk factors. This study aimed to evaluate the effects of SC or DC on blood pressure (BP) and microvascular function (MVF) in the postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (2908 kJ (695 kcal); 48 % fat): high DC (HDCM; 547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (LCM; 42 mg DC). BP was continuously evaluated from 15 min before to 120 min after meals by digital photoplethysmography. Before and 120 min after meals, participants underwent evaluation of serum Ca and microvascular flow after postocclusive reactive hyperaemia (PORH) by laser speckle contrast imaging. Ionised serum Ca rose significantly only after HSCM. Systolic BP increased after the three meals, whereas diastolic BP increased after LCM and HDCM. Hyperaemia peak, hyperaemia amplitude and AUC evaluated after PORH decreased with LCM. After HDCM, there was a reduction in hyperaemia peak and hyperaemia amplitude, whereas HSCM decreased only hyperaemia peak. However, comparative analyses of the effects of three test meals on serum Ca, BP and MVF revealed no significant meal×time interaction. This study suggests that in obese women SC and DC do not interfere with the effects of a high-fat meal on BP and MVF.

Low fruit consumption and omission of daily meals as risk factors for increased blood pressure in adults.

A population-based cross-sectional survey with cluster sampling design and with inverse sampling was conducted in 2010, in a sample of 1590 adults (19-60 years old) exposed to a high prevalence of food insecurity, in the municipality of Duque de Caxias, metropolitan region of Rio de Janeiro, Brazil. The objective of the study was to evaluate the association of socio-demographic factors, the consumption of fruits and vegetables and the number of meals with increased blood pressure (BP). A hierarchical model that considered variables related to the basic, intermediate and immediate determinants of increased BP was adopted. By using Poisson's regression, univariate models were tested to obtain the prevalence ratio (PR) and its respective 95 % CI. After fitting the model, age (age group 50-59 years) (PR 1·62; 95 % CI 1·09, 2·41), low consumption of fruits in a week (PR 1·37; 95 % CI 1·07, 1·74), fewer meals per day (PR 1·72; 95 % CI 1·21, 2·43) and overweight (PR 1·78; 95 % CI 1·31, 2·20) remained significantly associated with increased BP. Therefore, the results found here reinforce the importance of encouraging and developing strategies that ensure access to healthy foods to minimise increased BP in similar populations.

Examining associations between dietary patterns and metabolic CVD risk factors: a novel use of structural equation modelling.

The association between dietary patterns and metabolic cardiovascular risk factors has long been addressed but there is a lack of evidence towards the effects of the overall diet on the complex net of biological inter-relationships between risk factors. This study aimed to derive dietary patterns and examine their associations with metabolic cardiovascular risk factors following a theoretic model for the relationship between them. Participants included 417 adults of both sexes, enrolled to the cross-sectional population-based study performed in Brazil. Body weight, waist circumference, high-sensitivity C-reactive protein, blood pressure, total cholesterol:HDL-cholesterol ratio, TAG:HDL-cholesterol ratio, fasting plasma glucose and serum leptin were evaluated. Food consumption was assessed by two non-consecutive 24-h dietary recalls adjusted for the within-person variation of intake. A total of three dietary patterns were derived by exploratory structural equation modelling: 'Traditional', 'Prudent' and 'Modern'. The 'Traditional' pattern had a negative and direct effect on obesity indicators (serum LEP, body weight and waist circumference) and negative indirect effects on total cholesterol:HDL-cholesterol ratio, TAG:HDL-cholesterol ratio and fasting plasma glucose. The 'Prudent' pattern had a negative and direct effect on systolic blood pressure. No association was observed for the 'Modern' pattern and metabolic risk factors. In conclusion, the 'Traditional' and 'Prudent' dietary patterns were negatively associated with metabolic cardiovascular risk factors among Brazilian adults. Their apparent protective effects against obesity and high blood pressure may be important non-pharmacological strategies for the prevention and control of obesity-related metabolic disorders and CVD.

Reduction in sodium intake is independently associated with improved blood pressure control in people with chronic kidney disease in primary care.

Decreasing sodium intake has been associated with improvements in blood pressure (BP) and proteinuria, two important risk factors for CVD and chronic kidney disease (CKD) progression. We aimed to investigate the role of sodium intake by examining the effect of changes in sodium intake over 1 year on BP and proteinuria in people with early stage CKD. From thirty-two general practices, 1607 patients with previous estimated glomerular filtration rate of 59-30 ml/min per 1.73 m² and mean age of 72.9 (sd 9.0) years were recruited. Clinical assessment, urine and serum biochemistry testing were performed at baseline and after 1 year. Sodium intake was estimated from early morning urine specimens using an equation validated for this study population. We found that compared with people who increased their sodium intake from ≤ 100 to >100 mmol/d over 1 year, people who decreased their intake from >100 to ≤ 100 mmol/d evidenced a greater decrease in all BP variables (Δmean arterial pressure (ΔMAP) = -7.44 (SD 10.1) v. -0.23 (SD 10.4) mmHg; P<0.001) as well as in pulse wave velocity (ΔPWV = -0.47 (SD 1.3) v. 0.08 (SD 1.88) m/s; P<0.05). Albuminuria improved only in albuminuric patients who decreased their sodium intake. BP improved in people who maintained low sodium intake at both times and in those with persistent high intake, but the number of anti-hypertensive increased only in the higher sodium intake group, and PWV improved only in participants with lower sodium intake. Decreasing sodium intake was an independent determinant of ΔMAP. Although more evidence is needed, our results support the benefits of reducing and maintaining sodium intake below 100 mmol/d (2.3-2.4 g/d) in people with early stages of CKD.