Analysis of the gut microbiota profile targeted to multiple hypervariable regions of 16S rRNA in a hypertensive heart failure rat model.

The gut microbiota, comprising a diverse community of microorganisms, significantly influences various aspects of health. Changes in the composition of the gut microbiota are implicated in adverse effects on host physiology, contributing to the pathogenesis of cardiovascular diseases, among others pathological conditions. Understanding the role of the gut microbiota in the context of heart failure is particularly important. In this regard, the spontaneously hypertensive heart failure (SHHF) rat is an adequate experimental model since exhibits many features in common with heart failure (HF) in humans. Recent advancements in next-generation sequencing (NGS) have greatly improved microbiome analysis. However, standardization and the adoption of best practices are essential to mitigate experimental variations across studies. This manuscript outlines a straightforward methodology for analyzing gut microbiota composition in SHHF rat fecal samples using 16S rRNA sequencing, emphasizing the relevance of gut microbiota in heart failure.

Are lead, cadmium and mercury risk factors for resistant hypertension?

BACKGROUND: Lead (Pb), cadmium (Cd) and mercury (Hg) are toxic trace elements that represent a public health problem as risk factors for cardiovascular disease and hypertension (HT) and could also contribute to the development of resistant hypertension (rHT) AIMS: To compare the blood concentrations of Pb, Cd and Hg in subjects with resistant and non-resistant HT and to define whether there is a relationship between its levels and rHT. METHODS: Cross-sectional study. Subjects aged ≥ 21 to ≤ 80 years with a body mass index < 40 kg/m2 were recruited on a discretionary basis from October 2001 to October 2004 in a hypertension unit of a tertiary hospital amongst those sent to the hypertension unit by their family physician. Resistant hypertension was defined according to the American Heart Association (AHA) criteria. Whole blood concentrations of Cd, Pb and Hg were measured by electrothermal atomic absorption spectrometry. RESULTS: 46 out of 73 included subjects (63%) suffered from rHT. Blood Pb median: HT 3.9 (IQR 2.7-5.2) vs. rHT 3.6 (IQR 2.8-6.0) µg/dL (p=0.941). Blood Cd median: HT 0.07 (IQR 0.07-0.80) vs. rHT 0.30 (IQR 0.07-0.65) µg/L (p=0.681). Blood Hg median: HT 7.9 (IQR 5.8-12.9) vs. rHT 7.3 (IQR 4.6-13.3) µg/L (p=0.611). Considering the 75th percentile of each element (Pb: 5.55 µg/dL, Cd: 0.75 µg/L, Hg: 13.15 µg/L), a multiple logistic regression analysis (adjusted for age, BMI, diabetes mellitus, clearance of creatinine and only for Cd the smoking habit) showed an OR = 3.44 (0.84-14.10, p=0.086) for Pb, OR = 1.80 (0.39-8.24, p=0.451), for Cd and OR = 2.31 (0.59-9.14, p=0.232) for Hg. Moreover, the stratified analyses showed that men with Pb ≥5.55 µg/dL have a 14 times higher risk of suffering from rHT (p=0.026). Interestingly, a 9-fold increased risk was found for non-obese subjects with elevated Pb levels, above 5.55 µg/dL (p=0.029). Also in men, the probability of suffering from rHT was more than 7 times higher if Cd levels were ≥ 0.75 µg/L (p=0.076). Most smokers had higher Cd levels, with a high risk of suffering from rHT (ORa 12.6 (0.8-200.2), p=0.072). CONCLUSION: A higher blood Pb levels, defined by the 75th percentile (Pb ≥ 5.55 µg/dL), is associated with a greater risk of suffering from rHT and to a lesser extent in the case of Cd and Hg.

Incidence of type 2 diabetes in the elderly in Central Spain: Association with socioeconomic status, educational level, and other risk factors.

AIMS: To analyze the incidence of type 2 diabetes (T2D) in Central Spain and its association with the socioeconomic status (SES), educational level, and other risk factors (RF) in the elderly population of three communities. METHODS: Data for 5278 elderly participants (≥65 years old) were obtained using a census population-based survey. There was a first and a second survey three years later. The association between SES, educational level, RF, and T2D incidence was analyzed. RESULTS: The incidence rate for T2D was 9.8/1000 person-years without gender differences. Incident T2D was associated with low SES and lower educational levels. Baseline and follow-up BMI were also the main RFs for T2D. Communities' incidence rates were: (1) Margarita, working-class area: 11.3/1000 person-years; (2) Arévalo, agricultural region: 10.1/1000 person-years and; (3) Lista, professional high-income class area: 7.6/1000 person-years. CONCLUSION: We found an incidence rate of 9.8/1000 person-years of T2D in the elderly population. The risk of T2D was associated with a lower income and educational level. An increase in BMI may mediate this association. Our results emphasize the necessity of strategies for the prevention of diabetes that includes an approach to SES, educational levels, and other RF among older individuals in Spanish community settings.

A Body Shape Index (ABSI) and Hip Index (HI) Adjust Waist and Hip Circumferences for Body Mass Index, But Only ABSI Predicts High Cardiovascular Risk in the Spanish Caucasian Population.

Background: Our aim in this study was to investigate if Hip index (HI) improves the identification of cardiovascular risk (CVR) beyond that achieved with either the waist-to-height ratio (WHtR) or body mass index (BMI)-adjusted waist circumference (A body shape index [ABSI]) in the Spanish Caucasian population. Methods: Three thousand eight hundred forty-four subjects (1754 males, response rate 75.8%) were included. Anthropometric indices (AIs) included were HI, ABSI, and WHtR. CVR was estimated using the Framingham, Systematic COronary Risk Evaluation (SCORE), and American College of Cardiology/American Heart Association (ACC/AHA) charts. Areas under the receiver operating characteristic curve (AUC) were obtained to evaluate the performance of AIs in detecting CVR. We also estimated the AIs' standardized Z-scores and compared them against the CVR. Results: AUC demonstrated that the best AI in males to estimate higher CVR according to Framingham and ACC/AHA charts was WHtR. In females, WHtR also achieved good performance and showed higher prediction capacity than the other AIs. After transforming to Z-scores, ABSI was the best linear predictor for CVR according to SCORE and ACC/AHA, although WHtR also proved to be good. HI did not associate with the measures of CVR. Conclusions: HI does not predict high CVR in the Spanish Caucasian Population. However, ABSI is directly and linearly related to high CVR, with a higher performance than WHtR when standardized and evaluated as a linear predictor.

The FTO obesity gene. Genotyping and gene expression analysis in morbidly obese patients.

BACKGROUND: Obesity has emerged as one of the most serious public health concerns in the twenty-first century. the fat mass and obesity associated gene (FTO) has been found to contribute to the risk of obesity in humans. Our aims in this study were to investigate the association of rs9939609 single nucleotide polymorphism (SNP) of the FTO gene with different obesity-related parameters, to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese and its correlations with other adipocytokine gene expressions. METHODS: The association between the rs9939609 FTO gene variant and obesity related parameters in 75 obese/morbidly obese adult patients and 180 subjects with body mass index (BMI) < 30 kg/m(2) (control group) was examined. Gene expression analyses: subcutaneous adipose tissue samples were obtained from 52 morbidly obese and five subjects with BMI < 30 kg/m(2). Visceral adipose tissue was also obtained from 35 morbidly obese patients. Weight, height, BMI, SBP, DBP, fasting glucose, lipid profile, proinsulin, insulin, leptin, and adiponectin (RIA) of patients were also obtained. Insulin resistance by HOMA(IR). rs9939609 of FTO genotyping using allele discrimination in real-time PCR. Genomic study of RNA extraction of adipose tissue and real-time PCR (RT-PCR) of adipocytokines and a housekeeping gene were quantified using TaqMan probes. Relative quantification was calculated using the DeltaDelta Ct formula. RESULTS: The minor-(A) allele frequency of rs9939609 FTO gene in the whole population was 0.39. A strong association between this A allele and obesity was found, even after age-sex adjustment (p = 0.013). We found higher levels of FTO mRNA in subcutaneous adipose tissue from morbidly obese than in the control group (p = 0.021). FTO gene expression was lower in visceral than in subcutaneous adipose depot. However, this finding did not reach the level of statistical significance. A negative correlation between subcutaneous FTO gene expression and serum triglyceride levels and a positive correlation with leptin, perilipin, and visfatin gene expressions was found. In the visceral adipose tissue, these positive correlations were statistically significant only for perilipin. CONCLUSIONS: Our results show: (1) A strong association between rs9939609 SNP of the FTO gene variant and obesity in Spanish morbidly obese adult patients; (2) positive correlations between FTO mRNA and leptin, perilipin, and visfatin gene expressions in subcutaneous adipose tissue; (3) FTO and perilipin gene expressions were positively correlated in visceral fat depot. Overall these results may suggest a role of FTO in the regulation of lipolysis as well as in total body fat rather in fat distribution patterns.

Body fat anthropometric indexes: Which of those identify better high cardiovascular risk subjects? A comparative study in Spanish population.

AIM: To determine the association of body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtr) and Body Shape Index (ABSI) with high cardiovascular risk (CVR), as well as to determine whether how strong are these relationships. MATERIAL AND METHODS: A cross-sectional study was carried out in Spanish Caucasian adults. 3,456 subjects completed the study, 45.78% males, aged < 65 years and non-diabetic subjects. Anthropometric/biochemical variables were measured. We determined ABSI based on WC adjusted for height and weight. High CVR was defined as ≥ 20% according to the Framingham chart, ≥ 5% with the SCORE chart, and ≥ 7.5% with the ACC/AHA guide. Areas under the receiver operating characteristic curves (AUCs) were estimated for each anthropometric measure. RESULTS: Most significant AUCs in males were: WHtr and ABSI for Framingham ≥ 20% and SCORE ≥ 5%. Also significant were WHtr, WC and ABSI for ACCA/AHA ≥ 7.5%. On the other hand, most significant AUCs in females were: WHtr and WC for Framingham ≥ 20%; and WHtr and WHR for SCORE ≥ 5%, WHtr, and WC for ACC/AHA guide ≥ 7.5%. CONCLUSIONS: Overall, the best anthropometric index identifying Spanish males and females who are at high risk for CV events is WHtr. ABSI was also found to be a good anthropometric index to predict high CVR in Spanish males according to FR, SCORE and ACC/AHA charts. For Spanish females, WC is a good anthropometric index according to FR and ACC/AHA guide, while WHR is better according to SCORE.

Prevalence, Treatment, and Associated Factors of Hypertension in Spain: A Comparative Study between Populations.

The prevalence and related factors of hypertensive subjects according to the resident area (rural versus urban) were investigated in two population-based studies from Spain. Medical questionnaires were administered and anthropometrics were measured, using standardized protocols. Hypertension was diagnosed in pharmacology treated subjects or those with blood pressure (BP) ≥140/90 mm Hg. Regarding BP control, it was defined as under control if BP was <140/90 or <140/85 mm Hg in type 2 diabetic subjects. Information on educational status, social class, smoking habit, and alcohol intake was obtained. 3,816 subjects (54.38 % women) were included. Prevalence of diagnosed hypertension was higher in women and showed no differences according to the living area (men: urban 21.88 versus rural 21.92 %, p = 0.986; women: urban 28.73 versus rural 30.01 %, p = 0.540). Women living in rural areas and men with secondary or tertiary education levels had a lower probability of being BP uncontrolled (OR (95 % CI): 0.501 (0.258-0.970)/p=0.040, 0.245 (0.092-0.654)/p=0.005, and 0.156 (0.044-0.549)/p=0.004, respectively). Urban young men (31-45 years) and medium aged women (46-60 years) were less BP controlled than their rural counterparts (41.30 versus 65.79 %/p=0.025 and 35.24 versus 53.27 %/p=0.002, respectively).

Metabolic syndrome, glucose tolerance categories and the cardiovascular risk in Spanish population.

We examined the prevalence of metabolic syndrome (MetS), glucose tolerance categories and risk factors of cardiovascular-disease (CVD) in the general Spanish population. We studied 3844 randomly sampled subjects (46% males) aged 35-74 years. Glucose tolerance categories were defined according to the 2003 ADA and MetS according to the Harmonized Consensus Criteria with waist circumference (WC) cut-off-points previously reported in Spanish population (≥94.5/≥89.5cm for males/females). The prevalences of normoglycemia (NG), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG and IGT considered together (IFG/IGT), and diabetes mellitus (DM) were 67.6/16.6/5.0/3.3, and 7.5%, respectively. The overall prevalence of MetS was 31.2%. In subjects with NG, IFG, IGT, IFG/IGT, and DM the MetS prevalence's were 16.3/57.1/31.5/66.1, and 74.4% (p<0.001), respectively. MetS was more common in males, older subjects, smokers, and/or individuals with obesity, IFG, IFG/IGT, DM, or insulin resistance (HOMA-IR ≥3.8). MetS was less prevalent in individuals with low alcohol intake and/or high education level. Regarding the risk level of CVD estimated by Framingham and SCORE risk charts, IGT had higher estimated CVD-risk than IFG and IFG/IGT. The presence of MetS increases the risk 4.85 times by Framingham and 2.43 times by SCORE. Prevalence of prediabetes (IFG/IGT) and MetS were 25% and 31.2% respectively. Prevalence of MetS has not changed in the past decade in Spanish females, but has slightly increased in males. We found that subjects with IGT showed a higher risk of CVD than IFG and IFG/IGT according to the Framingham and SCORE. MetS increased the CVD-risk previously estimated by Framingham and SCORE.

Obesity and Cardiovascular Risk: Variations in Visfatin Gene Can Modify the Obesity Associated Cardiovascular Risk. Results from the Segovia Population Based-Study. Spain.

OBJECTIVES: Our aim was to investigate if genetic variations in the visfatin gene (SNPs rs7789066/ rs11977021/rs4730153) could modify the cardiovascular-risk (CV-risk) despite the metabolic phenotype (obesity and glucose tolerance). In addition, we investigated the relationship between insulin sensitivity and variations in visfatin gene. MATERIAL AND METHODS: A population-based study in rural and urban areas of the Province of Segovia, Spain, was carried out in the period of 2001-2003 years. A total of 587 individuals were included, 25.4% subjects were defined as obese (BMI ≥30 Kg/m2). RESULTS: Plasma visfatin levels were significantly higher in obese subjects with DM2 than in other categories of glucose tolerance. The genotype AA of the rs4730153 SNP was significantly associated with fasting glucose, fasting insulin and HOMA-IR (Homeostasis model assessment-insulin resistance) after adjustment for gender, age, BMI and waist circumference. The obese individuals carrying the CC genotype of the rs11977021 SNP showed higher circulating levels of fasting proinsulin after adjustment for the same variables. The genotype AA of the rs4730153 SNP seems to be protective from CV-risk either estimated by Framingham or SCORE charts in general population; and in obese and non-obese individuals. No associations with CV-risk were observed for other studied SNPs (rs11977021/rs7789066). CONCLUSIONS: In summary, this is the first study which concludes that the genotype AA of the rs4730153 SNP appear to protect against CV-risk in obese and non-obese individuals, estimated by Framingham and SCORE charts. Our results confirm that the different polymorphisms in the visfatin gene might be influencing the glucose homeostasis in obese individuals.

Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.

Profile of individuals who are metabolically healthy obese using different definition criteria. A population-based analysis in the Spanish population.

BACKGROUND: Obesity is associated with numerous metabolic complications such as diabetes mellitus type 2, dyslipidemia, hypertension, cardiovascular diseases and several forms of cancer. Our goal was to compare different criteria to define the metabolically healthy obese (MHO) with metabolically unhealthy obese (MUHO) subjects. We applied Wildman (W), Wildman modified (WM) with insulin resistance (IR) with cut-off point ≥ 3.8 and levels of C- Reactive Protein (CRP) ≥ 3 mg/l; and Consensus Societies (CS) criteria. In these subjects cardiovascular-risk (CV-risk) was estimated by Framingham score and SCORE for MHO and MUHO. METHODS: A cross-sectional study was conducted in Spanish Caucasian adults. A total of 3,844 subjects completed the study, 45% males, aged 35-74 years. Anthropometric/biochemical variables were measured. Obesity was defined as BMI: ≥ 30 Kg/m(2). RESULTS: The overall prevalence of obesity in our population was 27.5%, (23.7%/males and 30.2%/females). MHO prevalence according to W, WM, and CS definition criteria were: 9.65%, 16.29%, 39.94% respectively in obese participants. MHO has lower waist circumference (WC) measurements than MUHO. The estimated CV-risks by Framingham and SCORE Project charts were lower in MHO than MUHO subjects. WC showed high specificity and sensitivity in detecting high estimated CV risk by Framingham. However, WHR showed high specificity and sensitivity in detecting CV risk according to SCORE Project. MHO subjects as defined by any of the three criteria had higher adiponectin levels after adjustment by sex, age, WC, HOMA IR and Framingham or SCORE risks. This relationship was not found for CRP circulating levels neither leptin levels. CONCLUSIONS: MHO prevalence is highly dependent on the definition criteria used to define those individuals. Results showed that MHO subjects had less WC, and a lower estimated CV-risk than MUHO subjects. Additionally, the high adiponectin circulating levels in MHO may suggest a protective role against developing an unhealthy metabolic state.

Metabolic syndrome, adiponectin, and cardiovascular risk in Spain (the Segovia study): impact of consensus societies criteria.

BACKGROUND: We aimed to investigate the prevalence of metabolic syndrome in rural and urban areas in the province of Segovia, Spain, and its relationship to lifestyle habits, cardiovascular risk, and serum adiponectin concentrations. METHODS: The study had a cross-sectional design and included 888 individual residents in the province of Segovia, Autonomous Community of Castilla-León. RESULTS: The age/sex standardized prevalence of the metabolic syndrome was by: (1) American Heart Association/National Heart Lung and Blood Institute criteria (AHA/NHLBI), 17%; (2) International Diabetes Federation (IDF), 24.3%; and (3) Consensus Societies/Joint Interim Statement (CS), 27.8%. A high correlation was found between the different criteria. No formal education [odds ratio (OR) 6.9 (2.4-20.2)] and primary education [6.7 (2.8-15.9)] were independently associated with metabolic syndrome. An inverse association with metabolic syndrome was found for subjects doing a high level of exercise during work [0.4 (0.2-0.7)] as well as those who were mild drinkers [alcohol intake of less than 15 grams/daily, 0.4 (0.3-0.8)]. Among subjects with low estimated cardiovascular risk, adiponectin levels are higher in those who do not meet criteria of metabolic syndrome. A total of 29.7% of subjects meeting CS criteria had >20% 10-year predicted risk of cardiovascular disease (CVD) by the Framingham risk score criteria [4.5 (2.4-8.5)]. CONCLUSIONS: Our results show: (1) A higher estimated prevalence of metabolic syndrome according to IDF and CS criteria. (2) Low educational level was independently associated with metabolic syndrome. A high level of physical activity and a daily alcohol intake of less than 15 grams/day were inversely associated with metabolic syndrome. (3) Metabolic syndrome increases the predicted CVD risk. (4) Adiponectin levels are not inversely related to insulin resistance in subjects with high cardiovascular risk and metabolic syndrome.