Theodore A. Kotchen

Dietary sodium affects blood pressure (BP) and vascular function. Animal studies suggest epigenetic changes (eg, DNA methylation) are involved. We hypothesized that sodium restriction induces methylation changes in T cells and arterioles in humans. Fifty subjects (49% women) were placed on 1200-mg sodium/day diet for 2 weeks. BP and brachial artery flow-mediated dilation were evaluated. Methylation sequencing (pre- and post-diet) was performed on T-cell (n=50) and biopsied arteriolar (n=10) DNA. RNA sequencing was also performed on arterioles (n=11). Over 2 weeks, mean sodium consumption was 946 mg/day. Average BP reductions after low-sodium intake were −8±13/−4±9 mm Hg ( P P =0.03). T-cell DNA was substantially more methylated than arterioles. The differentially methylated regions (false discovery rate, P =0.009 for the overlap). The dietary effects on methylation in several DNA regions were associated with dietary effects on BP. Several differentially expressed genes in arterioles contained differentially methylated regions at the significance level of P P =0.03 for the overlap). Sodium restriction significantly affected DNA methylation in T cells and arterioles, some of which are associated with BP. Methylation patterns and sodium effects on methylation are largely tissue specific but also have overlaps between tissues and species. These findings may lead to better understanding of dietary sodium interactions with cellular processes and, therefore, novel therapeutic targets.

In 2015, the American Heart Association awarded 4-year funding for a Strategically Focused Research Network focused on hypertension composed of 4 Centers: Cincinnati Children’s Hospital, Medical College of Wisconsin, University of Alabama at Birmingham, and University of Iowa. Each center proposed 3 integrated (basic, clinical, and population science) projects around a single area of focus relevant to hypertension. Along with scientific progress, the American Heart Association put a significant emphasis on training of next-generation hypertension researchers by sponsoring 3 postdoctoral fellows per center over 4 years. With the center projects being spread across the continuum of basic, clinical, and population sciences, postdoctoral fellows were expected to garner experience in various types of research methodologies. The American Heart Association also provided a number of leadership development opportunities for fellows and investigators in these centers. In addition, collaboration was highly encouraged among the centers (both within and outside the network) with the American Heart Association providing multiple opportunities for meeting and expanding associations. The area of focus for the Cincinnati Children’s Hospital Center was hypertension and target organ damage in children utilizing ambulatory blood pressure measurements. The Medical College of Wisconsin Center focused on epigenetic modifications and their role in pathogenesis of hypertension using human and animal studies. The University of Alabama at Birmingham Center’s areas of research were diurnal blood pressure patterns and clock genes. The University of Iowa Center evaluated copeptin as a possible early biomarker for preeclampsia and vascular endothelial function during pregnancy. In this review, challenges faced and successes achieved by the investigators of each of the centers are presented.

Background: Dietary sodium (Na) and central adiposity are considered important risk factors for hypertension (HTN). Blood pressure (BP) levels are discordant among 40-50% of monozygotic (MZ) twin pairs. One prior study of MZ twins using questionnaires reported that hypertensive (HT) MZ twins differed in their intake of meat and milk. However, none of the previous studies have evaluated the impact of Na intake on BP in MZ twins. Methods: Eighty-eight pairs of MZ twins were enrolled from Milwaukee, WI and Michigan State University Twin Registry, East Lansing, MI (age- 44 ± 9 years, 63% women, and 96% Caucasian). BPs (measured in triplicate and averaged) and anthropometrics were measured. Na intake was calculated using Block Sodium Screener. Twin pairs were considered concordant or discordant based on systolic (SBP) or diastolic BP (DBP) difference of 10 mm Hg between co-twins, off BP medications Results: Thirty-seven twin pairs were discordant in their BP levels. Mean (± SD, mm Hg) SBP/DBPs among concordant and discordant twins were 120 ± 12 / 77 ± 9 and 131 ± 18 / 81 ± 10 respectively. Mean differences in SBP/DBP among concordant and discordant twins were 5 ± 7 / 4 ± 4 and 14 ± 8 / 10 ± 6 respectively. Discordant twins as a group had higher waist circumference (WC) compared to concordant twins (pConclusions: Higher Na intake is associated with higher BPs among MZ twins with discordant BPs. Differences in Na intakes were significant independent of central adiposity indicating significant Na sensitivity in discordant MZ twin pairs. The effect of ~500mg less Na intake/day in resulting in lower BPs in genetically identical individuals, suggests that modest decreases in Na-intake in Na-sensitive individuals may be sufficient to see the desired effect on BP levels.

This Viewpoint discusses the potential influence of precision medicine that incorporates epigenetic analysis in effectively treating hypertension.

Based on the expectation that measures of central blood pressure (CBP) and arterial function would be superior to standard sphygmomanometry for predicting cardiovascular risk, a number of devices have been introduced for the noninvasive estimation of CBP and pulse wave velocity (PWV).^1,2 However, questions have been raised about the validity and reliability of some of the methodologies and about their added clinical value.³ Consequently, there is currently ambiguity about the introduction of these measurements into routine clinical practice. The American Journal of Hypertension (AJH) welcomes the submission of manuscripts that address these issues.

A high prevalence of uncontrolled hypertension among Blacks is a major cause of racial health disparities in the United States. We established a community/academic partnership to improve hypertension control in Blacks receiving medical care at a federally qualified health center in Milwaukee. The defining components of our program included: six group sessions (one/month), based on the American Heart Association's Simple Seven curriculum and designed to motivate and empower patients to manage their blood pressure; active involvement of a community health worker; and ongoing participation of a community advisory board. The study design included a matched control group not exposed to the intervention. Patients in both groups received their usual medical care. Overall, compared to baseline, systolic blood pressure decreased at both 6 and 12 months (P < 0.004); however, the reduction of blood pressure in the intervention and control groups did not differ significantly (P = .62). Based on written responses to a questionnaire and structured focus group interviews after completing the six-month program, participants reported that the intervention was effective. In retrospect, they suggested that more attention might have been given to spirituality and stress reduction. Larger and longer-term studies will be required to evaluate the added value of this type of intervention.