- Agreement between finger plethysmography- and brachial oscillometry-derived blood pressure measurements. [Journal Article]
- CPClin Physiol Funct Imaging 2017 Apr 26
- CONCLUSIONS: These findings indicate that systolic and mean BP measurements made by brachial oscillometry do not agree with those from finger plethysmography. In contrast, diastolic BP values show acceptable agreement.
- Impact of switching from different treatment regimens to a fixed-dose combination pill (polypill) in patients with cardiovascular disease or similarly high risk. [Journal Article]
- EJEur J Prev Cardiol 2017 Jan 01; :2047487317695616
- Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails s...
Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different patterns of prior medication regimen. Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15% were randomised to polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline medications were classified by potency relative to polypill components. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomised trials. Results For cholesterol reduction conferred by polypills, there was a dose response across baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8 mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similar results were seen among patients taking 3 BP-lowering agents at baseline. Switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing. Conclusion Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care across a wide variety of treatment patterns, including equally potent or more potent regimens. The benefits of switching to polypill-based care were greatest among those stepped up from partial treatment or less potent treatment.
- 19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium. [Journal Article]
- NGNeurol Genet 2017; 3(1 Suppl 1):S2-S11
- The CHARGE consortium is an investigator-initiated collaboration to facilitate meta-analyses of genome-wide association studies (GWAS) and genomic analyses based on next generation sequencing (NGS), ...
The CHARGE consortium is an investigator-initiated collaboration to facilitate meta-analyses of genome-wide association studies (GWAS) and genomic analyses based on next generation sequencing (NGS), among multiple large and well-phenotyped population-based cohort studies around the world (http://www.chargeconsortium.com). Within the neuro-CHARGE working group, we are presenting an update of ongoing genomic studies on MRI-markers of cerebrovascular disease. Large population-based studies have shown that the burden of cerebrovascular disease extends far beyond that of clinical stroke. MRI-markers of cerebral small vessel disease, such as white matter hyperintensities (WMH), small subcortical brain infarcts, microbleeds, or dilated perivascular spaces, are particularly frequent in older community persons. These markers portend an increased risk of stroke, dementia, and premature death, and were shown to have a high heritability, especially WMH burden. Interestingly recent work has revealed genetic risk variants between WMH burden and stroke. To account for the major role of high blood pressure in the occurrence of WMH, we are performing a GWAS of WMH burden stratified on hypertension status, as well as a joint meta-analysis to account for gene-environment interaction with hypertension. Moreover, based on prior epidemiologic and histologic data suggesting that the pathogenesis of WMH may differ according to their location, we are running separate GWAS for periventricular and deep WMH burden. A GWAS of cerebral microbleeds is being finalized. We are also exploring the role of vascular risk factors in the occurrence of dementia by examining the relation of genetic risk scores for these factors with MRI-markers of brain aging and cerebrovascular disease. Finally, several NGS projects are being conducted to identify rare variants associated with WMH burden and lacunar brain infarcts. Additional projects are also currently being designed, including GWAS of novel MRI phenotypes, such as composite measures of cerebral small vessel disease, as well as lifetime, and epigenomic approaches.
- Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats. [Journal Article]
- NNutrients 2017 Apr 20; 9(4)
- Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-ge...
Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0.1). In the HF-diet exposed offspring, 54% of the annotated genes showed the gene-activating mark trimethylated lysine 4. Many of these genes (1) are associated with the "metabolic process" in general and particularly with "positive regulation of cholesterol biosynthesis" (FDR = 0.03); (2) overlap with 455 quantitative trait loci for blood pressure, body weight, serum cholesterol (all, FDR < 0.1); and (3) are linked to cardiac disease susceptibility/progression, based on disease ontology analyses and scientific literature. These results indicate that maternal HF-diet changes the cardiac histone signature in offspring suggesting a fuel-mediated epigenetic reprogramming of cardiac tissue in utero.
- Are genetic polymorphisms in the renin-angiotensin-aldosterone system associated with essential hypertension? Evidence from genome-wide association studies. [Review]
- JHJ Hum Hypertens 2017 Apr 20
- In candidate gene era, dozens of single-nucleotide polymorphisms (SNPs) within renin-angiotensin-aldosterone system (RAAS) have been reported to be significantly associated with hypertension. However...
In candidate gene era, dozens of single-nucleotide polymorphisms (SNPs) within renin-angiotensin-aldosterone system (RAAS) have been reported to be significantly associated with hypertension. However, the unbiased genome-wide association studies (GWAS) rarely identified the SNPs within RAAS were associated with hypertension or blood pressure (BP) traits. In order to figure out whether genetic polymorphisms of RAAS are really associated with hypertension, we systemically searched the GWAS Catalogue and identified all the known RAAS genes and relevant diseases/traits. After data processing, we found that polymorphisms within REN, AGT, ACE2, CYP11B2, ATP6AP2 and HSD11B2 were not associated with any disease or trait. SNPs within ACE, AGTR1, AGTR2, MAS1, RENBP and NR3C2 were associated with other diseases or traits, but showed no direct connection with hypertension. The only SNP associated with a BP trait, systolic BP was rs17367504. However, it is located in the intronic region of MTHFR near many plausible candidate genes, including CLCN6, NPPA, NPPB and AGTRAP. Therefore, the effect of RAAS polymorphisms may have been overestimated during the 'candidate gene era'. In the time of 'precision medicine', the power of RAAS variants needs to be reconsidered when evaluating one's susceptibility of hypertension.Journal of Human Hypertension advance online publication, 20 April 2017; doi:10.1038/jhh.2017.29.
- The Evaluation of Trauma Care: The Comparison of 2 High-Level Pediatric Emergency Departments in the United States and Turkey. [Journal Article]
- PEPediatr Emerg Care 2017 Apr 18
- CONCLUSIONS: This is the first study that compared pediatric trauma care and outcome at a level 1 pediatric trauma center in the United States and a pediatric hospital in Turkey. Our findings highlight the opportunities to improve pediatric trauma care in Turkey. Specifically, there is a need for national trauma registries, enhanced trauma education, and standardized trauma patient care protocols. In addition, efforts should be directed toward improving prehospital care through better integration within the health care system and physician participation in educating prehospital providers. Data and organized trauma care will be instrumental in system-wide improvement and developing appropriate injury-prevention strategies.
- Genomic Approaches to Hypertension. [Review]
- CCCardiol Clin 2017; 35(2):185-196
- Genomic insights and analyses of Mendelian hypertension (HTN) syndromes and Genome-Wide Association study (GWAS) on essential hypertension have contributed to the depth of understanding of the geneti...
Genomic insights and analyses of Mendelian hypertension (HTN) syndromes and Genome-Wide Association study (GWAS) on essential hypertension have contributed to the depth of understanding of the genetics origins of hypertension. Mendelian syndromes are important for the field, since such knowledge leads to specific insights about disease pathogenesis and the potential for precision medicine. The clinical impact of findings of on essential hypertension is continuously evolving, and the insights accrued will refine efforts to combat the societal impact of hypertension. Comprehensive identification of all genomic variants of hypertension, along with their individual associated mechanisms, is paving the way forward in the era of personalized medicine. The overriding challenge for care providers is to reduce health inequities through improved compliance and, perhaps, new paradigms for implementation science that incorporate genomic medicine.
- The contribution of urbanization to non-communicable diseases: Evidence from 173 countries from 1980 to 2008. [Journal Article]
- EHEcon Hum Biol 2017 Mar 27; 26:151-163
- It is widely believed that the expanding burden of non-communicable diseases (NCDs) is in no small part the result of major macro-level determinants. We use a large amount of new data, to explore in ...
It is widely believed that the expanding burden of non-communicable diseases (NCDs) is in no small part the result of major macro-level determinants. We use a large amount of new data, to explore in particular the role played by urbanization - the process of the population shifting from rural to urban areas within countries - in affecting four important drivers of NCDs world-wide: diabetes prevalence, as well as average body mass index (BMI), total cholesterol level and systolic blood pressure. Urbanization is seen by many as a double-edged sword: while its beneficial economic effects are widely acknowledged, it is commonly alleged to produce adverse side effects for NCD-related health outcomes. In this paper we submit this hypothesis to extensive empirical scrutiny, covering a global set of countries from 1980-2008, and applying a range of estimation procedures. Our results indicate that urbanization appears to have contributed to an increase in average BMI and cholesterol levels: the implied difference in average total cholesterol between the most and the least urbanized countries is 0.40mmol/L, while people living in the least urbanized countries are also expected to have an up to 2.3kg/m(2) lower BMI than in the most urbanized ones. Moreover, the least urbanized countries are expected to have an up to 3.2p.p. lower prevalence of diabetes among women. This association is also much stronger in the low and middle-income countries, and is likely to be mediated by energy intake-related variables, such as calorie and fat supply per capita.
- Genetic Effects on the Correlation Structure of CVD Risk Factors: Exome-Wide Data From a Ghanaian Population. [Review]
- GHGlob Heart 2017 Apr 10
- Plasma concentration of plasminogen activator inhibitor-1 (PAI-1) is highly correlated with several cardiovascular disease (CVD) risk factors. It also plays a direct role in CVD, including myocardial...
Plasma concentration of plasminogen activator inhibitor-1 (PAI-1) is highly correlated with several cardiovascular disease (CVD) risk factors. It also plays a direct role in CVD, including myocardial infarction and stroke, by impeding the dissolution of thrombi in the blood. Insofar as PAI-1 links CVD's risk factors to its endpoints, genetic variants modulating the relationship between PAI-1 and risk factors may be of particular clinical and biological interest. The high heritability of PAI-1, which has not been explained by genetic association studies, may also, in large part, be due to this relationship with CVD risk factors. Using exome-wide data from 1,032 Ghanaian study participants, we tested for heterogeneity of correlation by genotype between PAI-1 and 4 CVD risk factors (body mass index, triglycerides, mean arterial pressure, and fasting glucose) under the hypothesis that loci involved in the relationship between PAI-1 and other risk factors will also modify their correlational structure. We found more significant heterogeneities of correlation by genotype than we found marginal effects, with no evidence of type I inflation. The most significant result among all univariate and multivariate tests performed in this study was the heterogeneity of correlation between PAI-1 and mean arterial pressure at rs10738554, near SLC24A2, a gene previously associated with high blood pressure in African Americans.
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- Enhancing Care Models to Capture Psychological Trauma. [Journal Article]
- JPJ Psychosoc Nurs Ment Health Serv 2017 Apr 01; 55(4):29-36
- Toxic levels of stress in childhood are an ongoing threat to public health. Traumatized children have special needs for health care to address their developmental, mental health, and medical problems...
Toxic levels of stress in childhood are an ongoing threat to public health. Traumatized children have special needs for health care to address their developmental, mental health, and medical problems, and mitigate risk for long-term health problems. Developmental trauma leads to increased use of medical, social, correctional, and mental health services. Longitudinal and retrospective studies link childhood trauma and adversity to academic difficulties, poor health, and low economic productivity in adulthood. Studies demonstrate a clear link among early childhood trauma, neglect, and malnutrition with somatic disease processes, such as high blood pressure, coronary heart disease, and diabetes. A wide range of care providers, from the emergency department to subspecialties, should consider enhancing their typical models of care to include the special needs of traumatized children and the adults they become. [Journal of Psychosocial Nursing and Mental Health Services, 55(4), 29-36.].