Low-Sodium DASH Diet Reduces Blood Pressure, Arterial Stiffness, and Oxidative Stress in Hypertensive HFPEF

Abstract

Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In ‘salt-sensitive’ HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155 to 138 mmHg, p=.02) and diastolic BP (79 to 72 mmHg, p=.04), 24-hour ambulatory systolic (130 to 123 mmHg, p=.02) and diastolic BP (67 to 62 mmHg, p=.02), and carotid-femoral pulse wave velocity (12.4 to 11.0 m/s, p=.03). Urinary F2-isoprostanes decreased by 31% (209 to 144 pmol/mmol Cr, p=.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of ‘salt-sensitive’ hypertension, a phenotype present in many HFPEF animal models, and suggest shared pathophysiological mechanisms linking these two conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.

Introduction

Heart failure with preserved ejection fraction (HFPEF) constitutes over half of heart failure (HF) in older adults, and its incidence and prevalence are increasing ¹. In contrast to heart failure with reduced ejection fraction (HFREF), HFPEF treatment remains empirical with guidelines based largely on expert consensus ². In part, therapeutic uncertainty reflects an incomplete understanding of how HFPEF develops and progresses. Systemic hypertension often contributes to characteristic cardiovascular remodeling, but the specific aspects of hypertension that predispose to HFPEF are undefined.

High dietary sodium intake predicts hypertension across populations ³, but only some individuals are ‘salt-sensitive,’ i.e. have blood pressure (BP) that changes with sodium intake ⁴. In salt-sensitive animal models, high-sodium feeding induces systemic hypertension, oxidative stress, and cardiovascular damage similar to human HFPEF ^5–8. Factors that predict human salt-sensitive hypertension closely match HFPEF demographics ^{1, 4, 9}, but no dietary modification studies have previously been reported in HFPEF.

The Dietary Approaches to Stop Hypertension (DASH) eating pattern is high in potassium, magnesium, calcium, and antioxidants ¹⁰. When combined with sodium restriction (DASH/SRD), this diet reduces BP, vascular stiffness, and systemic oxidative stress in salt-sensitive humans without HF ¹¹. We hypothesized that three weeks of the DASH/SRD would have similar effects in HFPEF patients with treated hypertension.

Methods

This investigation conforms with the Declaration of Helsinki, was approved by the University of Michigan Institutional Review Board, followed institutional guidelines, and obtained written informed consent from all subjects.

Patient selection and study structure

The inclusion and exclusion criteria (see Table S1) were patterned after the 2007 European Society of Cardiology HFPEF diagnostic guidelines ¹². All subjects had a history of systemic hypertension, left ventricular ejection fraction ≥ 50%, and evidence of ventricular diastolic dysfunction by catheterization, echocardiography, and/or neurohormonal measures. Specific exclusions related to the DASH/SRD included estimated glomerular filtration rate < 30 ml/min/1.73 m², and current serum potassium > 5.0 mmol/L (or prior ≥ 6.0 mmol/L). Based on prior reports ¹¹, we estimated that 12 subjects would give > 80% power to detect a 10 mmHg reduction in clinic systolic BP and a 20% reduction in urinary 8-epi-PGF2α-isoprostane levels (F2-isoprostanes).

The study took place over 25 days, with two days of testing prior to and following 21 days of DASH/SRD (see Figure S1 for timeline). On Day 1, patients presented on their habitual diet after their usual morning medications. Baseline diet was assessed with the Block food frequency questionnaire ¹³. Seated clinic BPs and six-minute walk testing were performed; patients returned home on their habitual diet for ambulatory BP measurement and 24-hour urinary collection. On Day 2, patients presented fasting and prior to taking morning antihypertensives; they underwent vascular testing, transthoracic echocardiography, and blood sampling.

Subjects were provided all food and beverages (except water, tea, and/or coffee) for the DASH/SRD beginning on Day 3, with a safety visit 4–6 days later. If orthostatic vital sign changes, overt hypovolemia, or worsening azotemia were observed, diuretics were withdrawn or reduced. Other antihypertensives were reduced or withdrawn only for systolic BP < 100 mmHg or severe orthostasis. Subjects were withdrawn for serum potassium > 5.7 mg/dL (mandated) or significant worsening of renal function (investigator discretion). On Days 24–25, patients had identical testing to Days 1–2.

Characteristics of study diet, tracking of dietary adherence

The study diet was prepared by research dietitians in a metabolic kitchen at the University of Michigan Clinical Research Unit. The intent was to match the DASH diet nutritional content and food types while maintaining a daily sodium intake of 50 mmol (1150 mg)/2100 kilocalories, the amount producing the largest BP reduction in the DASH-Sodium trial ¹⁰. Caloric content was adjusted for expected energy needs to maintain lean body mass. In patients with estimated glomerular filtration rate < 60 ml/min/1.73 m², study diet potassium content was reduced from 4 to 3 g/day as suggested by the National Kidney Foundation ¹⁴.

Study food was packaged for storage, with pre-meal preparation (heating, etc.) completed at home by the patient. Subjects were advised not to ingest non-study foods or beverages, but were not required to consume all of the provided food. Adherence was assessed with a three-day food diary (at the midpoint) and pre-post DASH/SRD 24-hour urinary sodium and potassium excretion.

Blood pressure, laboratory, cardiovascular, and functional testing

Two seated clinic BPs were obtained per Joint National Committee (Seventh Report) recommendations ¹⁵. Ambulatory BP monitoring was performed per British Society of Hypertension guidelines ¹⁶ using the Spacelabs 90207 monitor (Spacelabs Healthcare, Issaquah, WA). Patient-reported sleep and wake times separated recordings into nighttime and daytime BPs. As in previous HF studies, the ‘non-dipping’ BP pattern was defined as a nighttime-to-daytime systolic BP ratio of ≥ 0.9¹⁷.

All laboratory testing was performed in the University of Michigan Health System clinical laboratory except urinary F2-isoprostanes, measured with a commercially available ELISA (Cayman Chemicals, Ann Arbor, MI).

Transthoracic echocardiography used the Acuson Sequoia C512 (Siemens USA, Malvern, PA) and carotid-femoral pulse wave velocity the Sphygmocor tonometer (AtCor Medical, Itasca, IL). Six-minute walk testing was performed per American Thoracic Society guidelines with Borg scores for dyspnea and fatigue.

Statistical analysis

Data are presented as the mean ± SD or median (IQR). Analysis was performed using STATA 10.0 (STATACorp, College Station, TX). Paired t-tests and Wilcoxon rank-sum tests were used for continuous and ordinal variables, respectively, with p < 0.05 considered statistically significant.

Results

Patient characteristics

The characteristics of the 14 enrolled participants (of 22 screened) are shown in Table 1. In addition to meeting study inclusion criteria, 13 of 14 subjects also fulfilled 2007 European Society of Cardiology HFPEF diagnostic guidelines (seven by catheterization and six via neurohormonal and/or echocardiographic criteria) ¹². Participants were primarily obese post-menopausal women with multiple comorbidities, and most had been previously hospitalized for decompensated HFPEF.

Table 1.

Baseline demographics and clinical characteristics of subjects

Demographics
Age (years)	72 ± 10
Gender (# female/male)	13/1
BMI (kg/m2)	35.5 ± 7.9
Baseline characteristics	n (%)	Comments
Hypertension	14 (100%)	No known secondary causes
Coronary artery disease	5 (36%)	1 with prior CABG, 1 with prior PCI
Diabetes mellitus	6 (43%)	All type II; Hgb A1c 6.8 ± 0.8%
Chronic kidney disease	14 (100%)	eGFR 60 ± 17 ml/min/1.73 m2
Stage II (eGFR 60–90)	6 (43%)
Stage III (eGFR < 60)	8 (57%)
Anemia	6 (43%)	Hematocrit 38 ± 5%
NYHA class III	12 (86%)
Prior heart failure hospitalization	10 (71%)
On chronic loop diuretic therapy	11 (79%)
On 3 antihypertensives *	10 (71%)

Abbreviations: BMI: body mass index; CABG: coronary artery bypass grafting; NYHA: New York Heart Association; eGFR: estimated glomerular filtration rate per Modification of Diet in Renal Disease; PCI: percutaneous coronary intervention

Thirteen patients completed the study; one was withdrawn due to serum potassium of 5.9 mmol/L at the safety visit. This subject’s electrolytes and renal function data are included in calculated pre-post mean values.

Study diet and adherence

A sample one-day DASH/SRD study menu is shown in Table S2. All subjects reported excellent DASH/SRD adherence per three-day food diaries, corroborated by increased urinary potassium excretion and halving of urinary sodium excretion from baseline in the 12 participants who were not on self-adjusted diuretic regimens (Table 2). A comparison of caloric and major nutrient intake between baseline and DASH/SRD diet is shown in Table S3. The mean weight loss during the study was 3.8 pounds.

Table 2.

Electrolytes and renal function pre- and post-dietary intervention

Parameter	Pre	Post	p
Serum sodium (mmol/L)*	141 ± 3	139 ± 3	.07
Serum potassium (mmol/L)*	4.5 ± 0.4	4.6 ± 0.6	.46
Serum creatinine (mg/dL)*	1.0 ± 0.2	1.2 ± 0.3	.02
Blood urea nitrogen (mg/dL)*	28 ± 13	41 ± 24	.03
24-hour creatinine clearance (ml/min/1.73 m2)	66 ± 35	57 ± 30	.11
Serum cystatin C (mg/dL)	1.34	1.41	.65
24-hour urinary sodium (mg/24 hr)	3353 ± 1593	1478 ± 933	<.001
24-hour urinary potassium (mg/24 hr)	2284 ± 793	2925 ± 1024	.04

^*One subject was withdrawn at safety visit for elevated serum potassium (see text); safety visit values for these parameters are included in ‘Post’ column

Blood pressure and medication changes

Baseline medications and changes during the study are shown in Table S4. All clinic and ambulatory BP recordings were adequate for analysis. In most subjects, baseline 24-hour monitoring demonstrated well-controlled BP consistent with HFPEF guidelines (systolic BP < 130 mmHg) ². The DASH/SRD significantly lowered clinic and 24-hour BP (Table 3). The number of patients with above-goal BP significantly decreased and there was a trend toward fewer subjects with non-dipping blood pressure following DASH/SRD.

Table 3.

Blood pressure pre- and post-dietary intervention

Clinic BP (mmHg)	Pre	Post	p
Systolic	155 ± 29	138 ± 22	.02
Diastolic	79 ± 15	72 ± 8	.04
Clinic systolic ≥ 130 mmHg	11/13	7/13	.01
24-hour ambulatory BP (mmHg)	Pre	Post	p
Systolic	130 ± 4	123 ± 4	.02
Diastolic	67 ± 3	62 ± 3	.02
BP non-dippers	10/13	7/13	.08
24-hour systolic ≥ 130 mmHg	7/13	4/13	.02

Abbreviations: BP, blood pressure

Laboratory studies

Serum sodium and measured creatinine clearance trended lower, blood urea nitrogen increased, and serum cystatin C was unchanged (Table 2). Urinary aldosterone excretion increased, but BNP and urinary F2-isoprostanes significantly declined (Table 2 and Figure, top panels). The change in urinary F2-isoprostanes correlated closely (r=0.76, p=.002) with the reduction in urinary sodium excretion on the DASH/SRD (Figure, bottom panel), but not with urinary aldosterone (r=−0.19, p=0.57). Upon exploratory stepwise regression, changes in urinary sodium excretion on DASH/SRD predicted urinary F2-isoprostane changes independent of baseline urinary sodium excretion and F2-isoprostane levels and weight change during the study.

Figure. Aldosterone and oxidative stress pre- and post-dietary intervention.

Whiskers: minimum/maximum values, line: median value, box: interquartile range

Cardiovascular and functional studies

All patients had normal left ventricular ejection fraction by transthoracic echocardiography (69 ± 6%; Simpson’s method in 11, estimated in two). The mean left atrial diameter was 42 mm. At baseline, six patients had grade II and four had grade I diastolic dysfunction, with two indeterminate (due to atrial fibrillation and suboptimal Doppler signal quality respectively) ¹⁸ and one ‘normal’ (with recent pulmonary capillary wedge pressure of 35 mmHg and BNP of 455 pg/mL). Twelve subjects had adequate signals for lateral and nine for septal mitral annulus tissue Doppler velocities; the DASH/SRD did not significantly alter E/e′ ratio (lateral 12 ± 2 to 11 ± 2, p=.45; septal 10 ± 3 to 9 ± 2, p=.14)

Twelve subjects had paired carotid-femoral pulse wave velocities (in one subject, data could not be obtained due to technical factors). Following DASH/SRD, pulse wave velocity remained stable in four, decreased by < 1.0 m/s in six, and increased by > 1.0 m/s in two participants. Pulse wave velocity increased by 6.7 m/s (50%) in one subject, nearly four standard deviations above the change in the other 11 patients. After excluding this extreme outlier, average pulse wave velocity significantly declined post-DASH/SRD (12.4 ± 3.0 to 11.0 ± 2.2 m/s, p=.03). Changes in pulse wave velocity did not significantly correlate with changes in systolic BP.

The baseline 6-minute walk test distance was similar to other outpatient HF cohorts, and modestly increased following DASH/SRD (313 ± 86 to 337 ± 91 m, p=.006). Borg dyspnea scores after the walk test improved slightly post-DASH/SRD [3.5 (2.5–5) to 3 (2–3), p=.049], but fatigue scores were unchanged [3 (1–4) to 3 (2–3), p = .43]. The number of patients reporting New York Heart Association Class III symptoms trended lower post-DASH/SRD (11/13 to 8/13, p=.17).

Discussion

Our study is the first to investigate the physiological effects of dietary modification in hypertensive HFPEF. As hypothesized, the DASH/SRD significantly reduced clinic BP, ambulatory BP, and arterial stiffness. Despite an expected increase in aldosterone production, urinary F2-isoprostane levels significantly declined in parallel to urinary sodium excretion following DASH/SRD.

Potential links between diet, salt-sensitive hypertension, and HFPEF

Dietary sodium ‘indiscretion’ frequently precipitates HF decompensation, particularly in elderly patients. However, dietary sodium reduction can increase neurohormonal activation, worsen renal function, and increase hospitalizations in patients with compensated HFREF ¹⁹. The possibility that dietary patterns contribute to HFPEF pathophysiology has not been extensively considered.

In the first National Health and Nutrition Examination Survey, high dietary sodium intake predicted incident HF only in overweight and obese respondents ²⁰. In a large cohort of postmenopausal women, the most common HFPEF demographic, incident HF was inversely related to DASH diet pattern adherence ²¹. Hospitalized HFPEF patients instructed to reduce dietary sodium at hospital discharge were less likely to be readmitted within 30 days ⁹. These studies suggest that dietary factors influence the pathogenesis of HFPEF.

Over three-quarters of HFPEF patients have systemic hypertension ^{1, 9}. Chronic high dietary sodium intake correlates with hypertension prevalence across disparate populations ³, and many advocate population-based dietary sodium restriction to prevent hypertension and its complications. However, only approximately 25% of normotensives and 30–50% of hypertensives are ‘salt-sensitive’, as defined by short-term BP changes between sodium-replete and deplete states ⁴. The BP threshold for salt-sensitivity, measurement protocols, and reproducibility of the sodium-BP response vary in the literature ^{4, 22}.

Despite these limitations, the salt-sensitive phenotype remains a useful construct to understand hypertensive cardiovascular disease. As in animal models ^5–8, independent of total BP load salt-sensitive humans develop cardiovascular abnormalities that are implicated in HFPEF. These include left ventricular hypertrophy and diastolic dysfunction, large-artery stiffening, and endothelial dysfunction. Clinical predictors of salt-sensitive BP include advanced age, the post-menopausal state, hypertension, abdominal obesity, insulin resistance, and chronic renal insufficiency ⁴; these demographics match those in large HFPEF cohorts ^{1, 9}.

Blood pressure effects of DASH-SRD

The magnitude of BP reduction following DASH/SRD in this study was greater than in untreated hypertensives ¹⁰ and prehypertensives ¹¹, comparable to adding an antihypertensive drug ²³, and occurred despite treatment with multiple antihypertensive agents in most subjects. By the end of the study, significantly more HFPEF patients met the guideline-recommended systolic blood pressure goal ². Moreover, in four of 13 subjects antihypertensives and/or diuretics were reduced shortly after starting the DASH/SRD (Table S3).

As expected ²³, the 24-hour BP reduction was smaller than in clinic BP but still notable. The BP ‘non-dipping’ pattern reflects impaired renal sodium handling and tracks closely with clinically demonstrated salt-sensitive BP ²⁴. Non-dipping BP doubles the risk of incident HF in older adults, independent of overall BP load and other clinical predictors ²⁵, and in HFREF patients increases cardiovascular hospitalization and death¹⁷. Ambulatory BP has not previously been reported in HFPEF. In this cohort, most patients were non-dippers despite diuretic treatment. The DASH/SRD restored normal BP dipping in three subjects, consistent with the effects of dietary sodium reduction in hypertensives without HF ²⁴.

Cardiovascular and functional effects of DASH-SRD

The classic conceptual model of HFPEF has expanded beyond ventricular diastolic dysfunction to encompass abnormalities in multiple cardiovascular domains. In particular, increased large-artery stiffness likely contributes to exercise intolerance and dyspnea in HFPEF. In this cohort, elevated pulse pressure and carotid-femoral pulse-wave velocity at baseline indicated significant large-artery stiffness. Previous studies demonstrated reduced arterial stiffness after three months of sodium restriction in postmenopausal women ²⁶ and following three weeks of the DASH/SRD in younger subjects with clinically confirmed salt-sensitive BP ¹¹. Our findings are consistent with these results, and were accompanied by a modest improvement in 6-minute walk distance and post-exercise dyspnea.

Echocardiographic diastolic function ¹⁸ did not significantly change following the DASH/SRD. The short study duration was unlikely to produce structural myocardial changes, and standard parameters such as E/e′ ratio may not be accurate enough to reflect serial differences in diastolic function or filling pressures in HFPEF ²⁷. More recently developed measures, such as diastolic strain rate, could potentially delineate subtle changes in diastolic function with dietary modification.

Aldosterone and oxidative stress effects of DASH/SRD

In salt-sensitive animals, high sodium feeding induces oxidative stress, which drives immune cell activation, perivascular inflammation, and fibrosis ^5–8. In these models, maintenance of normal or low dietary sodium intake largely prevents hypertension and end-organ pathology. Dietary supplementation with potassium, magnesium, calcium, and/or antioxidants reduces oxidative stress, inflammation, and cardiovascular damage even if high sodium intake continues ^{5, 28, 29}. The DASH/SRD, low in sodium and high in potassium, magnesium, calcium, and antioxidants, reduces systemic oxidative stress in salt-sensitive humans but does not in ‘salt-resistant’ persons, i.e. those whose BP changes little in response to sodium intake ^{11, 30}.

Given reduced sodium and increased potassium intake, we expected that the DASH/SRD would increase aldosterone, generally viewed as a strong pro-oxidant stimulus ^{5, 31}. In salt-sensitive experimental models, genomic and non-genomic mineralocorticoid effects often mediate end-organ damage. However, high mineralocorticoid levels in these animals do not cause severe adverse effects unless accompanied by elevated oxidative stress ^{5, 31}. In this study, urinary F2-isoprostanes did not correlate with aldosterone excretion; rather, they were closely related to the reductions achieved in urinary sodium excretion on the DASH-SRD. Our findings are consistent with a prior study in salt-sensitive humans without HF where the DASH/SRD reduced systemic oxidative stress despite more than doubling serum aldosterone levels¹¹.

In HFREF, systemic oxidative stress predicts functional class, increases during decompensation, and decreases following HF treatment ^{32, 33}. In this cohort, the baseline urinary F2-isoprostane excretion was comparable to that reported in HFREF patients ³² and decreased by over 30% following the DASH/SRD. In hypertensives without HF, increased systemic oxidative stress predicts reduced exercise capacity, ventricular hypertrophy and diastolic dysfunction, and endothelial dysfunction ^{34, 35}. Venous endothelial biopsy directly links oxidative stress and vascular dysfunction in older adults with metabolic syndrome, a demographic precursor to HFPEF ³⁶. In addition, heightened oxidative stress is present in the myocardium of HFPEF patients and is thought to drive cytokine production and myofibroblast differentiation ³⁷. These observations imply that oxidative stress is a key etiological component of HFPEF; our findings suggest a potential method to ameliorate this mechanism.

Safety

The DASH/SRD has not previously been studied in HF or chronic kidney disease (100% of our cohort). Four patients developed orthostasis requiring medication adjustment, and one was withdrawn for elevated serum potassium despite DASH/SRD modification as suggested by the National Kidney Foundation ¹⁴. In contrast to a prior study of sodium reduction in HFREF ¹⁹, where high-dose loop diuretics were continued, we adjusted diuretics at a safety visit based on clinical status. Although no subject was removed from participation due to renal dysfunction, blood urea nitrogen levels increased and creatinine clearance trended lower following DASH/SRD (Table 2). These changes are consistent with plasma volume reduction, also suggested by the modest weight loss on the isocaloric study diet. The lack of change in cystatin C implies that the DASH/SRD did not cause renal injury. Nonetheless, significant renal dysfunction can occur during sodium restriction in HF ¹⁹, and this short-term study highlights the importance of close renal monitoring during dietary modification.

Study limitations

Our results are hypothesis-generating and not necessarily generalizable to all HFPEF patients, such as those with non-hypertensive etiology or different demographics. The study group was enriched in characteristics that predict salt-sensitivity (e.g. advanced age, diabetes, obesity, renal insufficiency, post-menopausal state) ⁴ and as such closely resembled patients in large HFPEF cohort studies ^{1, 9}. In this small cohort, we were unable to determine whether specific factors contributed disproportionately to the salt-sensitive phenotype. Since extracardiac comorbidities contribute to the pathophysiology of HFPEF ³⁸, defining these relationships is an important area for future research.

In this pilot study, we used dietary intervention to reveal similarities between the salt-sensitive phenotype and hypertensive HFPEF. Our study is analogous to an early study of exercise training in HFPEF demonstrating safety and proof of concept ³⁹ that subsequently led to larger randomized trials ⁴⁰. To place our results in context, the effect sizes for blood pressure and oxidative stress were consistent with previous DASH diet studies in non-HF cohorts, which showed no clinic or ambulatory BP changes with habitual or control diets ^{41, 42}. In particular, the observed difference in 24-hour blood pressure in this study is unlikely to be due to a placebo effect ^{23, 41}. Nonetheless, our findings should now be verified and expanded upon in the context of a randomized trial.

We do not know which specific DASH/SRD components (e.g. sodium reduction, increased potassium, antioxidant intake) contributed to the observed effects. We did not hospitalize subjects to formally control dietary intake. However, we provided all food and beverages for the DASH/SRD, and urinary measures and food diaries indicated excellent dietary adherence. It is unknown whether our short-term results could be sustained in a cohort with complete freedom of food choice. Future, longer-term studies could include ongoing dietary education and other measures to support adherence.

Perspectives.

HFPEF is a major public health challenge currently without evidence-based therapy, largely due to incomplete understanding of its pathophysiology. Experimental models and HFPEF epidemiology suggest that dietary patterns and salt-sensitive hypertension play important roles. In this cohort of patients with hypertensive HFPEF, three weeks of the sodium-restricted DASH diet significantly reduced clinic and ambulatory BP, arterial stiffness, and oxidative stress. These observations are characteristic of salt-sensitive hypertension, a phenotype present in nearly all animal models of HFPEF. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.

Novelty and Significance.

What is New?

• Recent studies implicate oxidative stress and vascular dysfunction as key factors in human hypertensive HFPEF

• No prior dietary modification studies have been reported in hypertensive HFPEF

What is Relevant?

• Animal models of HFPEF display a salt-sensitive phenotype, with diet-induced oxidative stress driving perivascular inflammation and fibrosis

• The demographics and comorbidities commonly found in HFPEF are strongly associated with blood pressure salt-sensitivity.

Summary

• In HFPEF patients with treated hypertension, the sodium-restricted DASH diet reduced blood pressure, arterial stiffness, and systemic oxidative stress

• These observations suggest links between human hypertensive HFPEF and the salt-sensitive blood pressure phenotype