Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults

成人高血压患者的线粒体健康、心血管风险和血压目标

基本信息

项目摘要

PROJECT SUMMARY The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive blood pressure (BP) targets significantly reduced risks of cardiovascular disease (CVD) and mortality, leading to new guidelines recommending a lower BP target of <130/80 mm Hg. However, intensive BP targets may increase the risk of adverse events from antihypertensive therapy. With widespread adoption of the new BP guidelines, there is an urgent need to evaluate whether there are subgroups of patients who may have an unfavorable balance of benefits and harms from intensive BP lowering. We propose an innovative approach to risk stratification that integrates traditional risk factors with novel information gleaned from mitochondrial DNA (mtDNA). Mitochondria are intracellular organelles that are essential for energy metabolism and stress adaptation. In animal models, mitochondrial dysfunction plays a fundamental role in aging, CVD, and neurodegenerative diseases. Because mitochondrial metabolism is vital to adapt positively to bioenergetic stressors such as BP lowering, measures of mitochondrial health may help to predict beneficial and adverse outcomes among adults undergoing intensive treatment for hypertension. Recent observational studies have linked novel mtDNA measures with several age-related outcomes, including risks of CVD, hypertension, death, dementia, and reduced functional status. However, the optimal methods for integrating data across the mitochondrial genome have not been established, nor have prior studies investigated the utility of mtDNA measures for identification of subgroups who may derive greatest benefits or harms from intensive BP targets. This proposal will leverage next-gen sequencing technology and machine learning analytics to develop and validate mtDNA risk scores that predict CVD risk, mortality risk, and longitudinal changes in cognitive and physical function in older adults. Our first Aim will implement a biologically-informed neural network among participants of the Health, Aging, and Body Composition Study (Health ABC; N=3,075) and the Lifestyle Interventions and Independence for Elders Study (LIFE; N=1,755) to develop two mtDNA risk scores for prediction of CVD and cognitive and physical function outcomes, while accounting for the competing risk of death. Our second and third Aims will validate these mtDNA risk scores in two landmark trials that evaluated the impact of intensive vs standard BP targets on cardiovascular outcomes: SPRINT (N=9,361) and Action to Control Cardiovascular Risk in Diabetes (ACCORD; N=2,488). We will then examine whether mitochondrial risk, assessed by these mtDNA scores, modifies the efficacy or safety of the BP interventions. This work will: 1) develop innovative methods for analysis of mitochondrial genomic data; 2) provide novel hypotheses regarding pathways linking mitochondrial health, CVD risk and functional status; and 3) explore the potential of mtDNA measures for personalized health interventions in older adults.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Vasantha Kolavennu Jotwani其他文献

Vasantha Kolavennu Jotwani的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Vasantha Kolavennu Jotwani', 18)}}的其他基金

Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
成人高血压患者的线粒体健康、心血管风险和血压目标
  • 批准号:
    10210130
  • 财政年份:
    2021
  • 资助金额:
    $ 71.44万
  • 项目类别:
Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
成人高血压患者的线粒体健康、心血管风险和血压目标
  • 批准号:
    10679021
  • 财政年份:
    2021
  • 资助金额:
    $ 71.44万
  • 项目类别:
Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
成人高血压患者的线粒体健康、心血管风险和血压目标
  • 批准号:
    10711393
  • 财政年份:
    2021
  • 资助金额:
    $ 71.44万
  • 项目类别:
Cannabis use and kidney health among veterans with coronary artery disease
患有冠状动脉疾病的退伍军人的大麻使用和肾脏健康
  • 批准号:
    10261058
  • 财政年份:
    2020
  • 资助金额:
    $ 71.44万
  • 项目类别:
Biomarkers of Drug-induced Kidney Injury in HIV
HIV 药物性肾损伤的生物标志物
  • 批准号:
    9351503
  • 财政年份:
    2016
  • 资助金额:
    $ 71.44万
  • 项目类别:
Biomarkers of Drug-induced Kidney Injury in HIV
HIV 药物性肾损伤的生物标志物
  • 批准号:
    9270400
  • 财政年份:
    2016
  • 资助金额:
    $ 71.44万
  • 项目类别:
Novel biomarkers of kidney injury in HIV-infected men
HIV感染者肾损伤的新生物标志物
  • 批准号:
    8958708
  • 财政年份:
    2014
  • 资助金额:
    $ 71.44万
  • 项目类别:
Novel biomarkers of kidney injury in HIV-infected men
HIV感染者肾损伤的新生物标志物
  • 批准号:
    8783329
  • 财政年份:
    2014
  • 资助金额:
    $ 71.44万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了