Multiomic Profiling in Black and White Populations Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Adults
Increased left ventricular (LV) mass is associated with adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect Black individuals. To understand the underlying mechanisms, we undertook a proteomic screen in a Black cohort and compared the findings to results from a White cohort.
We measured 1305 plasma proteins using the SomaScan platform in 1772 Black participants (mean age, 56 years; 62% women) in JHS (Jackson Heart Study) with LV mass assessed by 2-dimensional echocardiography. Incident HF was assessed in 1600 participants. We then compared protein associations in JHS to those observed in White participants from FHS (Framingham Heart Study; mean age, 54 years; 56% women).
In JHS, there were 110 proteins associated with LV mass and 13 proteins associated with incident HF hospitalization with false discovery rate <5% after multivariable adjustment. Several proteins showed expected associations with both LV mass and HF, including NT-proBNP (N-terminal pro-B-type natriuretic peptide; β=0.04; P=2×10−8; hazard ratio, 1.48; P=0.0001). The strongest association with LV mass was novel: LKHA4 (leukotriene-A4 hydrolase; β=0.05; P=5×10−15). This association was confirmed on an alternate proteomics platform and further supported by related metabolomic data. Fractalkine/CX3CL1 (C-X3-C Motif Chemokine Ligand 1) showed a novel association with incident HF (hazard ratio, 1.32; P=0.0002). While established biomarkers such as cystatin C and NT-proBNP showed consistent associations in Black and White individuals, LKHA4 and fractalkine were significantly different between the two groups.
We identified several novel biological pathways specific to Black adults hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and fractalkine.
Left ventricular hypertrophy (LVH) represents a major worldwide disease burden: it complicates 18% to 41% of the estimated 65 million cases of hypertension.1 Despite the fact that hypertension is a notable LVH risk factor, LVH represents an independent mortality risk beyond blood pressure alone, raising mortality risk 6-fold to 8-fold, even in the presence of a normal ejection fraction.2,3 LVH has a diverse range of risk factors in addition to hypertension including age, weight, diabetes, obesity, hyperlipidemia, and smoking. Race is also associated with risk; Black individuals in particular experience an increased burden of LVH. Findings from HyperGEN (Hypertension Genetic Epidemiology Network) and the Dallas Heart Study suggest that the prevalence of LVH is at least 2-fold higher in Black individuals compared with White individuals.4
Specific cardiovascular outcomes are similarly heterogeneous. Namely, LVH is an independent risk factor for myocardial ischemia, stroke, heart failure (HF), and sudden cardiac death. However, not all individuals with LVH experience all of these complications.5 Furthermore, the mechanisms by which LVH progresses to HF remain unclear. Treatment response is also diverse; while it has been shown that antihypertensive treatment can reduce LVH over time, and that this reduction improves mortality, in the LIFE trial (Losartan Intervention for Endpoint Reduction in Hypertension), 23% of participants still had LVH after 5 years.6 The heterogeneity of outcomes and treatment effects likely stems from complex interplay between environmental and genetic effects, particularly given the fact that the pathophysiologic mechanisms of LVH involve multiple molecular pathways at the level of the myocytes, kidneys, and the sympathetic nervous system.7–9
Given the heterogeneity of risks, outcomes, and treatment effects, particularly when comparing Black and White individuals, it is essential that we explore the underlying pathophysiologic processes of LVH in more depth specifically in a Black population. Proteomic screening provides a way to interrogate multiple biologic pathways simultaneously. Recent advances in aptamer-based proteomic technologies enable high-throughput profiling of low-abundance analytes in large epidemiological cohorts.10–12 While some proteomic screens have been performed in mouse and rat models of LVH and in White human populations,13–16 there is a paucity of data describing the associations between the human proteome and LVH in Black populations, despite their increased burden of disease.
We, therefore, undertook a proteomic screen of JHS (Jackson Heart Study)—a large population-based cohort comprised of Black participants from the Jackson, MS community to better understand the pathophysiology of LVH and incident HF. We then compared our findings to those from FHS (Framingham Heart Study) to test for potential differences. Finally, we leveraged genetic and metabolomic data from JHS to corroborate these findings.
All proteomics data are available through dbGaP: JHS accession phs000964/phs002256.v1.p1 and FHS accession phs000007.v31.p12, requiring access request. JHS metabolomics data have been submitted to the JHS Data Coordinating Center and to dbGaP; until posted in dbGaP, all JHS data are available from the JHS Data Coordinating Center on request.
The human study protocols were approved by the Institutional Review Boards of the Beth Israel Deaconess Medical Center, Boston University Medical Center, and University of Mississippi Medical Center, and all participants provided written informed consent.
Full Methods are available as a Data Supplement.
Baseline Characteristics in JHS
A total of 2145 individuals from JHS had proteomic profiling (Figure 1). These individuals were clinically similar to JHS as a whole (n=5306; Table I in the Data Supplement). Of this group with profiling, 1772 had echocardiography. After indexing to height, 301 (17%) had LVH by the American Society of Echocardiography criteria (Table 1). Individuals with LVH were more likely to be older, women, hypertensive, overweight, have diabetes, have a history consistent with coronary heart disease, and have lower estimated glomerular filtration rate. Ejection fraction and low-density lipoprotein cholesterol levels were similar.
|No LVH (n=1471)||LVH (n=301)||No HF (n=1448)||HF (n=152)||No LVH (n=925)||LVH (n=280)||No HF (n=1437)||HF (n=160)|
|Age, y||55 (12)||62 (11)||55 (12)||65 (11)||53 (10)||57 (10)||54 (10)||63 (8)|
|Women, n||868 (59%)||238 (79%)||900 (62%)||101 (66%)||492 (53%)||185 (66%)||774 (54%)||71 (44%)|
|Hypertension, n||876 (60%)||256 (85%)||866 (60%)||123 (81%)||237 (26%)||138 (49%)||456 (32%)||106 (66%)|
|Systolic blood pressure, mm Hg||126 (17)||135 (21)||126 (18)||134 (19)||123 (18)||132 (20)||125 (18)||140 (20)|
|Hypertensive medication, n||730 (50%)||239 (79%)||731 (50%)||112 (74%)||126 (14%)||70 (25%)||239 (17%)||75 (47%)|
|Diabetes, n||275 (19%)||93 (31%)||246 (17%)||66 (43%)||33 (3.6%)||27 (9.6%)||75 (5.2%)||46 (29%)|
|Hemoglobin A1c, %||6.0 (1.2)||6.3 (1.5)||5.9 (1.2)||6.5 (1.7)||5.3 (0.8)||5.6 (1.0)||5.4 (0.9)||6.3 (1.7)|
|Body mass index, kg/m2||31 (7)||35 (8)||32 (7)||33 (8)||26 (4)||29 (5)||27 (5)||30 (6)|
|Estimated glomerular filtration rate, mL/min per 1.73 m2||84 (19)||78 (23)||85 (18)||74 (24)||91 (19)||87 (22)||90 (19)||81 (23)|
|LDL cholesterol, mg/dL||127 (37)||126 (37)||127 (37)||129 (42)||125 (33)||127 (34)||126 (33)||128 (35)|
|History of CAD, n||74 (5.0%)||37 (12%)||57 (3.9%)||15 (9.9%)||13 (1.4%)||11 (3.9%)||18 (1.3%)||17 (11%)|
|Ejection fraction, %||62 (7)||63 (10)||62 (7)||62 (8)||67 (7)||67 (9)||67 (7)||62 (13)|
|LV mass index, g/m2.7||32.9 (6.0)||54.2 (9.9)||35.4 (9.5)||42.0 (12.1)||36.1 (6.2)||51.9 (6.7)||39.3 (8.8)||44.8 (10.5)|
|Current smoker, n||183 (12%)||37 (12%)||160 (11%)||24 (16%)||165 (18%)||50 (18%)||286 (20%)||25 (16%)|
Of 1600 individuals with proteomic profiling, clinical covariates, and without prevalent HF at baseline, 152 (10%) were hospitalized for incident HF during a median of 11 years of follow-up. The pattern of comorbidity burden in the HF group was similar to that of the LVH group (Table 1).
Protein Associations With Left Ventricular Mass
We used linear models to assess the association between 1305 proteins and left ventricular (LV) mass. In an age- and sex-adjusted model, 381 proteins were associated with LV mass with false discovery rate (FDR) <5% (Table II in the Data Supplement). After adjustment for age, sex, body mass index, estimated glomerular filtration rate, systolic blood pressure, presence of hypertension, presence of diabetes, total/high-density lipoprotein cholesterol, history of myocardial infarction, and current smoking status, 110 proteins were associated with LV mass with FDR <5% (Figure 2; Table III in the Data Supplement). As expected, NT-proBNP (N-terminal pro-B-type natriuretic peptide; β=0.04 [0.02–0.05]; P=2×10−8) was strongly associated with LV mass. This association held true among obese individuals (data not shown). Many of the protein-LVH associations were novel, including LKHA4 (leukotriene-A4 hydrolase; change in ln[LV mass] per SD change in protein level, β=0.05 [0.03–0.06]; P=5×10−15) and PRKACA (cAMP-dependent protein kinase catalytic subunit alpha; β=0.03 [0.02–0.04]; P=6×10−8). Proteins with the strongest inverse association with LV mass included carbonic anhydrase (β=−0.03 [−0.04 to −0.02]; P=8×10−8) and 6-phosphogluconate dehydrogenase (β=−0.03 [−0.04 to −0.02]; P=4×10−7). Modeling LV mass indexed to height2.7 did not significantly affect the results (Table IV in the Data Supplement).
Protein Associations With Incident HF
The association between protein levels and incident HF was assessed using Cox-proportional hazards models. In an age- and sex-adjusted model, 111 proteins were associated with incident HF with FDR <5%. In a multivariable adjusted model (same covariates as above, as well as interim myocardial infarction), 13 proteins were associated with FDR <5% (Figure 3; Tables V and VI in the Data Supplement). These included well-described biomarkers such as cystatin C (hazard ratio [HR], 1.66 [1.35–2.04]; P=1×10−6) and NT-proBNP (HR, 1.48 [1.22–1.81]; P=0.0001). Cardiotrophin-1, angiopoeitin-2, troponin I, and troponin T were all associated with incident HF as well, as expected, though at levels of significance below the stated threshold in adjusted models (P=0.001, P=0.001, P=0.004, P=0.006, respectively). Growth hormone receptor (HR, 0.68 [0.56–0.83]; P=0.0001) and galectin-3 (HR, 0.74 [0.62–0.87]; P=0.0004) showed negative associations with incident HF. More novel findings included fractalkine (HR, 1.32 [1.14–1.53]; P=0.0002). Only NT-proBNP, galectin-3, cystatin C, and β2 microglobulin had an association with both LV mass and incident HF in adjusted models at an FDR <5%.
Comparing Protein Associations Between JHS and FHS
To understand differences in protein associations between Black and White cohorts, we compared the effect sizes of those proteins associated with LV mass or incident HF in JHS (at FDR <5% in multivariable adjusted models) to FHS. In the subset of FHS patients that could be evaluated for incident HF (n=1597; Figure 1), subjects had notably less hypertension and hypertension treatment, less diabetes, and less obesity but overall more coronary heart disease (Table 1). Over a median of 21 years, 160 patients developed HF.
For proteins associated with LV mass in JHS, the majority showed directionally consistent associations in FHS (Figure I in the Data Supplement). Figure 4 shows proteins associated with LV mass in JHS with a Bonferroni-adjusted difference in effect size when compared with FHS. LKHA4, alanine aminotransferase 1, HSP70 (heat shock 70 kDa protein 1A), cysteine and glycine-rich protein 3, and neurexophilin-1 were associated with increased LV mass and had effect sizes that differed from FHS at a Bonferroni-adjusted level of significance. Serine/threonine protein kinase 17B, MMP7 (matrilysin), matrix MMP9 (metalloproteinase-9), bactericidal/permeability-increasing protein, peptidyl-prolyl cis-trans isomerase D, and high mobility group protein B1 also had significant differences from FHS but were inversely associated with LV mass. For comparison, renin and NT-proBNP showed no significant differences: renin was inversely associated with LV mass in both cohorts, whereas NT-proBNP was directly associated with LV mass.
Given the significant differences, we leveraged data from an alternate, antibody-based proteomics platform to support these findings. Of the 11 proteins that differed from FHS, 5 are measured by the Olink platform and were available in a subset of 458 individuals from JHS. Despite reduced power (due to one-quarter the samples), LKHA4, MMP7, and HSP70 showed significant and consistent associations with LV mass while MMP9 was directionally consistent; neurexophilin-1’s association was inconsistent with the aptamer-based data (Table VII in the Data Supplement).
Fewer differences between the cohorts were seen for proteins associated with incident HF (Figure 5). Growth arrest-specific protein 1 and fractalkine/CX3CL1 (C-X3-C Motif Chemokine Ligand 1) levels were associated with a higher risk of incident HF in JHS compared with FHS, while growth hormone receptor was associated with a lower risk of incident HF in JHS compared with FHS. However, only growth arrest-specific protein 1 met the Bonferroni-adjusted significance threshold. These relationships were not evaluated using Olink given the smaller sample size and reduced HF events, limiting power.
HF With Preserved Ejection Fraction Versus Reduced Ejection Fraction
We compared HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), to explore proteins more strongly associated with specific subtypes of HF. Of the 1836 individuals without prevalent HF in whom HF status could be followed, there were 78 cases of HFrEF and 88 cases of HFpEF (Figure 1). Fourteen cases of HF had an indeterminate type and were excluded. In competing risk analysis, 324 proteins were associated with at least 1 subtype of HF at P<0.05 (Table VIII in the Data Supplement). When compared, 41 proteins showed a difference in risk estimate between HFpEF and HFrEF at FDR <10% (Figure 6). Hexokinase-2 levels were associated with a decreased risk of HFpEF but with increased risk of HFrEF (HR for HFrEF, 1.22 [1.07–1.38] per SD change in protein level; P=0.003; HR for HFpEF, 0.80 [0.67–0.95]; P=0.01; P for difference, 6×10−4). Alternatively, killer cell immunoglobulin-like receptor 3DS1 showed the opposite pattern of association (HR for HFpEF, 1.24 [1.07–1.43]; P=0.004; HR for HFrEF, 0.73 [0.56–0.96]; P=0.02; P for difference, 8×10−4). Proteins including cystatin C and NT-proBNP were associated with increased risk for both types of HF and, therefore, were not significantly different between the two groups (Figure 6).
Associations Between Arachidonic Acid Oxidation Products and Cardiac Phenotypes in JHS
LKHA4 catalyzes the conversion of leukotriene A4 to leukotriene B4 in a reaction which lies downstream of the conversion of arachidonic acid to multiple signaling molecules. Using available metabolomics profiling in JHS, we identified 6 metabolites downstream of arachidonic acid metabolism. While leukotriene A4 and B4 could not be measured due to low abundance, multiple eicosanoids were measured. We determined each metabolite’s partial correlation with LKHA4 after adjustment for age and sex, as well as their association with both LV mass and incident HF after adjustment for all of the previously noted clinical covariates. With the exception of Arachidonic acid, all metabolites were significantly correlated with LKHA4. Much like LKHA4, each metabolite was directly associated with LV mass, but none were associated with incident HF (Table 2). The strongest association was that of the mono-HETEs, which, during profiling, group together as a single peak (Pearson correlation with LKHA4, 0.27; P=1×10−23; β for association with ln(LV mass), 0.03; P=5×10−5; HR for incident HF, 1.17; P=0.20).
|Metabolite||Pearson correlation with LKHA4 (95% CI)||P value||β for association with ln(LV mass) (95% CI)||P value||HR for incident HF (95% CI)||P value|
|Arachidonic acid||0.02 (−0.03 to 0.07)||0.44||0.02 (0.01 to 0.04)||5.0×10−4||0.98 (0.76 to 1.26)||0.89|
|5-Oxo-ETE||0.18 (0.13 to 0.23)||6.4×10−11||0.02 (0.00 to 0.03)||0.02||1.07 (0.82 to 1.39)||0.62|
|12-Oxo-ETE||0.20 (0.15 to 0.25)||2.4×10−13||0.02 (0.01 to 0.03)||0.006||1.11 (0.85 to 1.45)||0.44|
|15-Oxo-ETE||0.21 (0.16 to 0.26)||1.3×10−14||0.02 (0.01 to 0.03)||0.003||1.14 (0.87 to 1.49)||0.35|
|14(15)-EET||0.26 (0.20 to 0.30)||4.2×10−21||0.02 (0.00 to 0.03)||0.01||1.15 (0.89 to 1.49)||0.29|
|11(12)-EET||0.27 (0.22 to 0.32)||1.8×10−23||0.02 (0.01 to 0.03)||0.005||1.15 (0.89 to 1.48)||0.28|
|HETE||0.27 (0.22 to 0.32)||1.3×10−23||0.03 (0.01 to 0.04)||4.6×10−5||1.17 (0.92 to 1.49)||0.20|
Both LVH and incident HF are associated with a myriad of upstream risk factors and downstream complications. Increased risk is associated with race,4 though the combined impact of social/structural, environmental, and genetic factors on pathobiology remains unclear.17 While proteomic profiling of HF has been performed in White populations,15,16,18 similar work is lacking in Black populations. Comparative profiling is critical to our understanding of the disease and its underlying pathways. To this end, our study utilizes the largest proteomic profiling of a Black population both in number of subjects and number of proteins profiled, 1305 proteins in 2145 individuals, and compares it to an equally large and well profiled White population. These individuals had high-quality echocardiographic phenotyping and rigorous adjudication of HF events, as well as detailed profiling of their comorbidities allowing for statistical adjustment in these heterogeneous disease states. Taken together, these results can form the basis for deeper exploration into the biology of LVH and incident HF.
We observed 110 proteins to be associated with LV mass, even after adjustment for multiple comorbidities and multiple comparisons, and 13 proteins associated with incident HF. Validating the platform, NT-proBNP was strongly associated with increased LV mass, as well as incident HF. Two other well-described renal markers showed a similar pattern, cystatin C and β2 microglobulin. These markers are known to be associated with LV mass in patients with chronic kidney disease,19–21 though the association has not previously been shown in community dwelling adults. By contrast, cystatin C is well known to be associated with incident HF and HF prognosis.22 Similar data for a relationship between β2 microglobulin and incident HF is weaker, though it does appear to be elevated once HF has developed.23,24 Interestingly, galectin-3—a known biomarker in HF and renal disease—showed an inverse association with LV mass and incident HF in both JHS and FHS, contrary to existing literature, which include data from FHS.25,26 This suggests the measurement of galectin-3 by the aptamer may differ from that of the ELISA. The aptamer’s specificity for galectin-3 is supported by genetic and mass spectroscopy data (Table IX in the Data Supplement); however, there are 4 known splice variants of galectin-3, so the specific variant detected by the aptamer may differ from ELISA. If signaling in HF is related to an increase in one variant relative to another, this may explain the result. Further investigation is certainly warranted.
Several proteins showed a strong association with LV mass but not with incident HF. The strongest association between any protein and LV mass was LKHA4. Specifically, this association was unique to the Black population. LKHA4 hydrolyzes leukotriene A4 to leukotriene B4, which exerts proinflammatory effects via the G-protein–coupled receptor BLT1 on leukocytes. This pathway has been implicated in vascular inflammation, and LKHA4 activity has been targeted in drug trials for atherosclerotic disease.27,28 These drugs proved ineffective, possibly due to concomitant inhibition of the enzyme’s anti-inflammatory capabilities.28 Despite a strong association with LV mass, it is not clear why LKHA4 was not associated with incident HF, nor a specific subtype of HF in our analyses. However, previous work shows an association with prevalent HF in a small cohort that included ≈25% Black participants.29 To explore the relationship more deeply, we utilized available profiling of metabolites downstream of arachidonic acid. Leukotriene A4 and leukotriene B4 are such metabolites but are low abundance and not well measured in the blood by liquid chromatography and mass spectrometry. However, arachidonic acid (a precursor to leukotriene A4) and other oxidation products of arachidonic acid are available, including mono-HETEs, epoxyeicosatrienoic acids, and oxoeicosatetraenoic acids. Interestingly, these oxidation products were both correlated with LKHA4 levels and associated with LV mass, but not associated with incident HF, a similar pattern to LKHA4 itself. Furthermore, phospholipase A2, which produces arachidonic acid, was not associated with either LV mass or incident HF after adjustment for clinical covariates. These data highlight pathways downstream of arachidonic acid as areas for further investigation rather than arachidonic acid metabolism as a whole. It may be that LKHA4 and related pathways are responsive to these disease states, rather than causative. Detailed profiling of the eicosanoid lipidome is of critical importance in future studies and, given the observed data, should ideally be performed in diverse populations.
Conversely, fractalkine/CX3CL1 was found to be associated with incident HF but not LV mass—an association that was notably stronger in JHS compared with FHS. Fractalkine is observed in both a membrane-bound and soluble form and is involved in chemoattraction and binding of peripheral inflammatory cells.30 It has been implicated in atherosclerosis, ischemia-reperfusion injury, and cardiomyopathy.30–32 Our data suggest that it has an independent association with incident HF hospitalization in an ambulatory Black population. The fact that many proteins associated with either LV mass or incident HF but not both fits with data suggesting the pathobiology of each may differ: drugs that improve LVH have not been shown to have benefit in HFpEF.33,34
Comparing subtypes of HF (HFpEF versus HFrEF), while exploratory given samples sizes, highlighted a substantial difference between the proteins associated with the HF syndrome as a whole. Those proteins associated most strongly with incident HF overall did not show a predilection for either type, highlighting the syndromic similarities between each subtype. Conversely, the proteins with significant difference between the two subtypes highlight the varying pathobiology between the two phenotypes. Hexokinase 2 and GDF (growth differentiation factor) 11 both showed a stronger association with HFrEF compared with HFpEF. Hexokinase 2 is known to attenuate cardiac hypertrophy when overexpressed in mice by modulating flux through the pentose phosphate pathway, which in turn modulates the reactive oxygen species, which contribute to hypertrophy.35 Similarly, GDF11, which has significant homology to GDF8/myostatin, is thought to modulate cardiac muscle mass. Recent data from experimental studies in mice suggest that GDF8/11 levels decline with age, and injection of GDF11 was able to reduce cardiac mass.36 Our data correlate with these findings, as levels of these proteins appeared to be protective of HFpEF. However, we also show the levels of these proteins associated with a risk of HFrEF—a consideration for any therapeutic targeting of these pathways. The fact that these proteins did not associate with LV mass in our data suggest that their role in humans may have less of an effect on actual cardiac mass and a greater effect on myocardial function.
There are several important limitations of our work. While the proteomic profiling discussed here is the most extensive in any Black cohort to date, it does not contain the entire proteome, and important protein associations may be missed as a result. LV mass was estimated by echocardiographic measurements, which are less accurate than newer methods such as cardiac magnetic resonance imaging. However, one would expect this to bias results to the null. In JHS, HF hospitalizations were not adjudicated until 2005, so there is a chance incident HF hospitalizations were not captured (in the interval between baseline and 2005). While 152 cases of incident HF is of acceptable size, we lacked power for anything more than an exploratory analysis of HFpEF and HFrEF. The mean follow-up time required to achieve comparable numbers of HF events between JHS and FHS is significant (11 versus 21 years), which could influence the difference in protein associations, though age adjustment should account for much of that influence. These event rates illustrate the greater risk in Black individuals. Our results cannot yet be externally validated owing to the unique nature of such extensive profiling in a cohort of Black individuals. However, the numerous positive controls, evidence of aptamer specificity, and multiomic associations we observed lend significant support to the validity of the platform and analytic approach.
Our results highlight several biological pathways hypothesized to contribute to the pathophysiologic cascade of LVH and incident HF. Elements of endovascular dysfunction and inflammation—manifested in these data by associations between LKHA4 and LV mass, as well as fractalkine and incident HF—may precede overt disease. Further studies are needed to validate these results and elucidate the detailed underlying mechanisms.
false discovery rate
Framingham Heart Study
growth differentiation factor
heart failure with preserved ejection fraction
heart failure with reduced ejection fraction
heat shock 70 kDa protein 1A
Hypertension Genetic Epidemiology Network
Jackson Heart Study
Losartan Intervention for Endpoint Reduction in Hypertension
left ventricular hypertrophy
N-terminal pro-B-type natriuretic peptide
cAMP-dependent protein kinase catalytic subunit alpha
We wish to thank the staffs and participants of the JHS (Jackson Heart Study). The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the US Department of Health and Human Services.
Sources of Funding
The JHS (Jackson Heart Study) is supported and conducted in collaboration with the Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I/HHSN26800001), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) and contracts from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute for Minority Health and Health Disparities. Dr Katz is supported by NHLBI T32 postdoctoral training grant (T32HL007374-40). Dr Tahir is supported by the Ruth L. Kirchstein postdoctoral individual National Research Award (F32HL150992). Dr Nayor is supported by NHLBI K23HL138260. Dr Cruz is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health [NIH]/National Center for Advancing Translational Sciences [NCATS] award TR002542). Dr Robbins and Dr Tahir are supported by the John S. LaDue Memorial Fellowship in Cardiology at Harvard Medical School. Dr Benson is supported by NHLBI K08HL145095 award. Drs Gerszten, Wang, and Wilson are supported by NIH R01 DK081572 and NIH R01 HL133870. Drs Gerszten, Wang, and Vasan are supported by NIH R01 HL132320.
Supplemental Tables I–IX
Supplemental Figure I
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