Dietary Prevention of Heart Failure in Hypertensive Metabolic Syndrome
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology, Endocrine |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 45 - Any |
| Updated: | 1/16/2019 |
| Start Date: | January 2, 2019 |
| End Date: | December 30, 2022 |
| Contact: | Alysia J Drummond, MPH RD CHES |
| Email: | Alysia.Drummond@va.gov |
| Phone: | (734) 222-7563 |
Tens of thousands of Veterans have heart failure with preserved ejection fraction (HFpEF),
and suffer poor quality of life, frequent hospitalizations, and high death rates. Older
Veterans and those with high blood pressure, obesity, and the metabolic syndrome (abnormal
cholesterol and resistance to insulin's effects) are particularly at risk for HFpEF. However,
it is not clear why only some Veterans in this risk group eventually develop HFpEF. Extensive
information from experimental animal models and some human studies suggests that dietary
patterns in vulnerable 'salt-sensitive' people could contribute to the risk for HFpEF.
Reducing salt intake and increasing overall dietary quality in at-risk Veterans could prevent
heart and blood vessel damage that ultimately leads to HFpEF. Reducing the development of
HFpEF, which currently has no definitive treatment, is highly relevant to the VA's mission to
emphasize prevention of disease and population health.
and suffer poor quality of life, frequent hospitalizations, and high death rates. Older
Veterans and those with high blood pressure, obesity, and the metabolic syndrome (abnormal
cholesterol and resistance to insulin's effects) are particularly at risk for HFpEF. However,
it is not clear why only some Veterans in this risk group eventually develop HFpEF. Extensive
information from experimental animal models and some human studies suggests that dietary
patterns in vulnerable 'salt-sensitive' people could contribute to the risk for HFpEF.
Reducing salt intake and increasing overall dietary quality in at-risk Veterans could prevent
heart and blood vessel damage that ultimately leads to HFpEF. Reducing the development of
HFpEF, which currently has no definitive treatment, is highly relevant to the VA's mission to
emphasize prevention of disease and population health.
Patients with heart failure (HF) account for over 1,200,000 VA outpatient visits per year,
and HF remains the most common cause for hospital admission in the VA. Approximately 1/3 of
Veterans with HF have 'preserved' ejection fraction (HFpEF), or relatively normal contractile
function of the heart; such patients suffer functional decline and poor quality of life, and
half die within 5 years after diagnosis. Risk factors for developing HFpEF are more common in
Veterans than the general population, and the burden of HFpEF to the VA system will rise in
the years ahead as these Veterans age. Preventive efforts are critical, but are hampered by
gaps in knowledge related to HFpEF pathophysiology. The long term goal of this proposal is to
prevent the onset of HFpEF in at-risk Veterans. Hypertension (HTN) confers the highest
population-attributable risk for HFpEF, particularly when accompanied by the metabolic
syndrome, a constellation of obesity, insulin resistance, and dyslipidemia. Animal models of
HTN and metabolic syndrome develop HFpEF due to microvascular oxidative stress and
inflammation induced by high sodium intake. Recent data from cardiac biopsies confirm similar
mechanisms in human HFpEF. Dietary sodium restriction is widely recommended to prevent
HTN-associated heart disease in humans, but this advice is now controversial. Few studies
have examined how individual differences in response to sodium intake affect risk.
"Salt-sensitive" persons have blood pressure (BP) that changes in parallel with sodium
intake, and commonly develop cardiovascular abnormalities associated with HFpEF. The overall
objective of this proposal is to evaluate salt-sensitivity as a novel, diet-responsive risk
factor for incident HFpEF in Veterans with HTN and metabolic syndrome. The central hypothesis
is that the sodium-restricted Dietary Approaches to Stop Hypertension (DASH/SRD) eating
pattern will improve cardiovascular functional and structural risk factors for HFpEF in
Veterans with the salt-sensitive phenotype. Guided by findings in experimental models, cohort
studies, and strong preliminary evidence from the investigators' research group, this
hypothesis will be tested in a two-phase study and by pursuing three specific aims: 1)
Determine effects of DASH/SRD on functional and structural cardiovascular HFpEF risk factors
in salt-sensitive vs. salt-resistant Veterans, 2) measure the effect of an
electronically-delivered tailored-messaging intervention on DASH/SRD adherence, and 3)
determine effects of DASH/SRD intervention and adoption on microvascular function and assess
the endothelial glycocalyx as a biomarker of cardiovascular response to DASH/SRD. Phase 1 of
the study is a crossover-randomized comparison of DASH/SRD vs. control diet for two weeks
each, and Phase 2 a 6-month extension to promote DASH/SRD adherence. The salt-sensitive
phenotype will be defined by between-diet changes in 24-hour mean BP during Phase 1. In Phase
2, the efficacy of motivational interviewing-based counseling and the Women's and Men's
Hypertension Experiences and Emerging Lifestyles Intervention (WHEELS-I), a tailored
messaging program, to sustain DASH/SRD adherence, will be compared. Echocardiography and
arterial tonometry will be used to assess HFpEF-related cardiovascular parameters during
short- and longer-term dietary modification and their interaction with salt-sensitivity. In
vivo microscopy and novel blood testing will assess microvascular function and the integrity
of the endothelial glycocalyx, a blood vessel lining that is sodium-responsive and may
mediate the adverse effects of salt-sensitivity. This proposal is innovative because it
represents the first study to examine salt-sensitivity as a factor promoting HFpEF in
Veterans with HTN and metabolic syndrome, the highest risk group for incident HFpEF.
Moreover, it aims to link microvascular dysfunction, an important pathway in human HFpEF,
with endothelial glycocalyx damage, a potential biomarker for sodium-mediated vascular risk.
The proposed research is significant because it will vertically advance the investigators'
understanding of how dietary factors contribute to the pathophysiology of HFpEF, a major and
growing health threat to Veterans.
and HF remains the most common cause for hospital admission in the VA. Approximately 1/3 of
Veterans with HF have 'preserved' ejection fraction (HFpEF), or relatively normal contractile
function of the heart; such patients suffer functional decline and poor quality of life, and
half die within 5 years after diagnosis. Risk factors for developing HFpEF are more common in
Veterans than the general population, and the burden of HFpEF to the VA system will rise in
the years ahead as these Veterans age. Preventive efforts are critical, but are hampered by
gaps in knowledge related to HFpEF pathophysiology. The long term goal of this proposal is to
prevent the onset of HFpEF in at-risk Veterans. Hypertension (HTN) confers the highest
population-attributable risk for HFpEF, particularly when accompanied by the metabolic
syndrome, a constellation of obesity, insulin resistance, and dyslipidemia. Animal models of
HTN and metabolic syndrome develop HFpEF due to microvascular oxidative stress and
inflammation induced by high sodium intake. Recent data from cardiac biopsies confirm similar
mechanisms in human HFpEF. Dietary sodium restriction is widely recommended to prevent
HTN-associated heart disease in humans, but this advice is now controversial. Few studies
have examined how individual differences in response to sodium intake affect risk.
"Salt-sensitive" persons have blood pressure (BP) that changes in parallel with sodium
intake, and commonly develop cardiovascular abnormalities associated with HFpEF. The overall
objective of this proposal is to evaluate salt-sensitivity as a novel, diet-responsive risk
factor for incident HFpEF in Veterans with HTN and metabolic syndrome. The central hypothesis
is that the sodium-restricted Dietary Approaches to Stop Hypertension (DASH/SRD) eating
pattern will improve cardiovascular functional and structural risk factors for HFpEF in
Veterans with the salt-sensitive phenotype. Guided by findings in experimental models, cohort
studies, and strong preliminary evidence from the investigators' research group, this
hypothesis will be tested in a two-phase study and by pursuing three specific aims: 1)
Determine effects of DASH/SRD on functional and structural cardiovascular HFpEF risk factors
in salt-sensitive vs. salt-resistant Veterans, 2) measure the effect of an
electronically-delivered tailored-messaging intervention on DASH/SRD adherence, and 3)
determine effects of DASH/SRD intervention and adoption on microvascular function and assess
the endothelial glycocalyx as a biomarker of cardiovascular response to DASH/SRD. Phase 1 of
the study is a crossover-randomized comparison of DASH/SRD vs. control diet for two weeks
each, and Phase 2 a 6-month extension to promote DASH/SRD adherence. The salt-sensitive
phenotype will be defined by between-diet changes in 24-hour mean BP during Phase 1. In Phase
2, the efficacy of motivational interviewing-based counseling and the Women's and Men's
Hypertension Experiences and Emerging Lifestyles Intervention (WHEELS-I), a tailored
messaging program, to sustain DASH/SRD adherence, will be compared. Echocardiography and
arterial tonometry will be used to assess HFpEF-related cardiovascular parameters during
short- and longer-term dietary modification and their interaction with salt-sensitivity. In
vivo microscopy and novel blood testing will assess microvascular function and the integrity
of the endothelial glycocalyx, a blood vessel lining that is sodium-responsive and may
mediate the adverse effects of salt-sensitivity. This proposal is innovative because it
represents the first study to examine salt-sensitivity as a factor promoting HFpEF in
Veterans with HTN and metabolic syndrome, the highest risk group for incident HFpEF.
Moreover, it aims to link microvascular dysfunction, an important pathway in human HFpEF,
with endothelial glycocalyx damage, a potential biomarker for sodium-mediated vascular risk.
The proposed research is significant because it will vertically advance the investigators'
understanding of how dietary factors contribute to the pathophysiology of HFpEF, a major and
growing health threat to Veterans.
Inclusion Criteria:
- Veterans aged 45 years with HTN
- here defined as screening systolic BP 130 and/or diastolic BP 85 mmHg, or current
use of anti-hypertensive drugs
- and metabolic syndrome
- body mass index 30 kg/m2 and/or waist circumference >94 cm
- Participants must also be willing to participate in the WHEELS-I program by using a
smartphone application or email
Exclusion Criteria:
- On-treatment systolic BP of >160 mmHg at screening visit
- previous history of HF
- left ventricular ejection fraction <50%
- moderate or severe valvular heart disease
- myocardial infarction or stroke within the prior 6 months
- chronic kidney disease with estimated glomerular filtration rate <45 ml/min/ 1.73m2
- unoperated aortic aneurysm for which surgery is indicated, prior hyperkalemia
requiring urgent treatment
- hemoglobin <9 gm/dL
- investigator-determined factors: severe pulmonary disease, e.g.:
- oxygen-requiring
- hepatic disease, e.g.:
- cirrhosis
- severely uncontrolled diabetes (hemoglobin A1c >10%)
- active cancer other than non-melanoma skin or low-risk prostate cancer
- other comorbidity with expected survival <12 months
- active alcohol/illicit substance abuse
- and/or a history of persistent nonadherence to treatment
- Veterans involved in another study (unless it is survey-only and the other
investigator will allow us to invite the person in a survey-only study to consider our
study)
We found this trial at
1
site
Ann Arbor, Michigan 48113
Principal Investigator: Scott L. Hummel, MD
Phone: 734-222-7563
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