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2.
J Am Soc Nephrol ; 30(10): 2027-2036, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31383730

RESUMO

BACKGROUND: Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. METHODS: We conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts. RESULTS: Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index. CONCLUSIONS: In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.

3.
Hum Mol Genet ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31127295

RESUMO

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

4.
J Am Heart Assoc ; 8(6): e011771, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30879408

RESUMO

Background Malaria exposure in childhood may contribute to high blood pressure ( BP ) in adults. We used sickle cell trait ( SCT ) and α+thalassemia, genetic variants conferring partial protection against malaria, as tools to test this hypothesis. Methods and Results Study sites were Kilifi, Kenya, which has malaria transmission, and Nairobi, Kenya, and Jackson, Mississippi, where there is no malaria transmission. The primary outcome was 24-hour systolic BP. Prevalent hypertension, diagnosed using European Society of Hypertension thresholds was a secondary outcome. We performed regression analyses adjusting for age, sex, and estimated glomerular filtration rate. We studied 1127 participants in Kilifi, 516 in Nairobi, and 651 in Jackson. SCT frequency was 21% in Kilifi, 16% in Nairobi, and 9% in Jackson. SCT was associated with -2.4 (95% CI , -4.7 to -0.2) mm Hg lower 24-hour systolic BP in Kilifi but had no effect in Nairobi/Jackson. The effect of SCT in Kilifi was limited to 30- to 59-year-old participants, among whom it was associated with -6.1 mm Hg ( CI , -10.5 to -1.8) lower 24-hour systolic BP. In pooled analysis allowing interaction by site, the effect of SCT on 24-hour systolic BP in Kilifi was -3.5 mm Hg ( CI , -6.9 to -0.1), increasing to -5.2 mm Hg ( CI , -9.5 to -0.9) when replacing estimated glomerular filtration rate with urine albumin to creatinine ratio as a covariate. In Kilifi, the prevalence ratio for hypertension was 0.86 ( CI , 0.76-0.98) for SCT and 0.89 ( CI , 0.80-0.99) for α+thalassemia. Conclusions Lifelong malaria protection is associated with lower BP in Kilifi. Confirmation of this finding at other sites and elucidating the mechanisms involved may yield new preventive and therapeutic targets.

5.
Nat Genet ; 51(4): 636-648, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926973

RESUMO

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.


Assuntos
Lipídeos/sangue , Lipídeos/genética , Fumar/sangue , Fumar/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Estilo de Vida , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Nat Commun ; 10(1): 376, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670697

RESUMO

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.


Assuntos
Exercício , Loci Gênicos/genética , Lipídeos/sangue , Lipídeos/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Brasil , Proteínas de Ligação ao Cálcio/genética , Colesterol/sangue , HDL-Colesterol/sangue , HDL-Colesterol/genética , LDL-Colesterol/sangue , LDL-Colesterol/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Hispano-Americanos/genética , Humanos , Proteínas com Homeodomínio LIM/genética , Metabolismo dos Lipídeos/genética , Masculino , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição/genética , Triglicerídeos/sangue , Triglicerídeos/genética , Adulto Jovem
7.
J Clin Endocrinol Metab ; 104(6): 2267-2276, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668751

RESUMO

BACKGROUND: 25-hydroxyvitamin D [25(OH)D] is lower in black compared with white Americans but is not consistently associated with outcomes in this group, possibly due to genetic and other biological differences. We examined the association of plasma 25(OH)D and renal outcomes in black Americans with a focus on effect modifiers. METHODS: We studied associations between baseline 25(OH)D with (i) annual rate of estimated glomerular filtration rate (eGFR) decline and (ii) incident chronic kidney disease (CKD) in the Jackson Heart Study, a prospective cohort of black Americans. Plasma 25(OH)D levels were corrected for monthly variation in sunlight exposure using the residual method. We used adjusted generalized linear models to evaluate outcomes and assessed potential effect modification by diabetes mellitus, vitamin D binding protein (DBP) genotype, obesity, dietary sodium intake, and use of renin-angiotensin-aldosterone system inhibitors. RESULTS: Among 5164 participants with 25(OH)D available, plasma 25(OH)D was 14.5 ± 6.5 ng/mL (mean ± SD), and eGFR was 94.1 ± 22.0 mL/min/1.73 m2. Over a median of 8 years, eGFR decline was 1.3 ± 2.0 mL/min/1.73 m2 per year in 3228 participants with complete data, and 220 out of 1803 eligible participants developed incident CKD. Overall, 25(OH)D was not associated with eGFR decline in fully adjusted models. However, higher 25(OH)D was associated with slower eGFR decline among those with diabetes: each 5 ng/mL higher 25(OH)D was associated with a 0.27 mL/min/1.73 m2/y slower eGFR decline (95% CI, 0.13 to 0.41; P < 0.001). Higher 25(OH)D was not associated with incident CKD overall, but it was associated with lower odds of incident CKD among participants with the GG or GT genotype at rs7041 in the gene encoding DBP [OR, 0.69 per 5 ng/mL higher 25(OH)D; 95% CI, 0.51 to 0.93; P-interaction = 0.005]. Other interactions were not significant. CONCLUSION: These findings support a potential benefit of higher 25(OH)D for kidney health in black Americans with diabetes or specific variants in DBP.

8.
Am J Epidemiol ; 188(6): 1033-1054, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698716

RESUMO

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

9.
Nat Commun ; 9(1): 5141, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30510157

RESUMO

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

10.
Circ Heart Fail ; 11(11): e005629, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30571193

RESUMO

BACKGROUND: Obesity is highly prevalent among blacks and is associated with a greater risk of heart failure (HF). However, the contribution of regional adiposity depots such as visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue toward risk of HF in blacks is unknown. METHODS AND RESULTS: We included 2602 participants (mean age: 59 years, 35% men) from the Jackson Heart Study without prevalent HF who underwent computed tomography quantification of VAT and subcutaneous adipose tissue during the second visit (2005-2009). The associations between different adiposity measures and HF were evaluated using adjusted Cox models. There were 122 incident HF events over a median follow-up of 7.1 years. Higher amounts of VAT were associated with greater risk of HF in age- and sex-adjusted analyses (hazard ratio [95% CI] per 1-SD higher VAT: 1.29 [1.09-1.52]). This association was attenuated and not significant after additional adjustment for traditional HF risk factors and body mass index. Overall obesity, represented by body mass index, was associated with higher risk of HF independent of risk factors and VAT (hazard ratio [95% CI] per 1-kg/m2 higher body mass index: 1.06 [1.02-1.11]). Subcutaneous adipose tissue was not associated with risk of HF in adjusted analyses. CONCLUSIONS: In a community-dwelling black population, higher amounts of overall and visceral adiposity are associated with higher risk of HF. The association between VAT and HF risk in blacks may reflect differences in traditional HF risk factor burden. Future studies are needed to confirm this observation and clarify the independent role of different measures of adiposity on HF outcomes.


Assuntos
Adiposidade/fisiologia , Insuficiência Cardíaca/fisiopatologia , Gordura Intra-Abdominal/patologia , Obesidade/patologia , Distribuição Tecidual/fisiologia , Afro-Americanos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Medição de Risco , Fatores de Risco
11.
Stress Health ; 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30407711

RESUMO

Leukocyte telomere length (LTL) is a biomarker of cellular aging. African Americans report more stress than other groups; however, the association of psychosocial stressors with biological aging among African Americans remains unclear. The current study evaluated the association of psychosocial factors (negative affect and stressors) with LTL in a large sample of African American men and women (n=2,516) from the Jackson Heart Study (JHS). Using multivariable linear regression, we examined the sex-specific associations of psychosocial factors (cynical distrust, anger-in and -out, depressive symptoms, negative affect summary scores, global stress, weekly stress, and major life events-MLEs, and stress summary scores) with LTL. Model 1 adjusted for demographics and education. Model 2 adjusted for model 1, smoking, alcohol intake, physical activity, diabetes, hypertension, and high-sensitivity C-reactive protein (hsCRP). Among women, high (vs. low) cynical distrust was associated with shorter mean LTL in model 1 (b = -0.12; p=0.039). Additionally, high (vs. low) anger-out and expressed negative affect summary scores were associated with shorter LTL among women after full adjustment (b = -0.13; p=0.011; b = -0.12, p=0.031, respectively). High levels of cynical distrust, anger out and negative affect summary scores may be risk factors for shorter LTL, particularly among African American women.

12.
J Am Heart Assoc ; 7(20): e009515, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30371273

RESUMO

Background Blacks have more severe endothelial dysfunction and aortic stiffening as compared with whites. We aimed to investigate the association between aortic stiffness and microvascular function in the black community. Methods and Results We assessed the association between forearm vascular reactive hyperemia (an indicator of microvascular function) and aortic stiffness in 1458 black participants (N=965 [66% women]; mean age: 66±11 years) in the Jackson Heart Study. We evaluated 2 measures of aortic stiffness: brachial pulse pressure and carotid-femoral pulse wave velocity. Using high-resolution ultrasound and Doppler, we evaluated brachial blood flow at baseline and during reactive hyperemia after 5 minutes of forearm ischemia. Multiple cardiovascular risk factors were significantly related to baseline and hyperemic brachial flow velocity. Women had lower baseline flow across the entire age spectrum. During hyperemia, we observed a significant age-sex interaction for flow velocity ( P=0.02). Female sex was protective against microvascular dysfunction among younger participants, but older women exhibited a greater attenuation of the hyperemic flow reserve. In multivariable models that adjusted for cardiovascular disease risk factors and mean arterial pressure, higher carotid-femoral pulse wave velocity (ß=-0.106±0.033; P=0.001 was related to lower baseline flow. However, during reactive hyperemia, elevated brachial pulse pressure (ß=-0.070±0.031; P=0.03) and carotid-femoral pulse wave velocity (ß=-0.128±0.030; P<0.001) were both related to attenuated brachial flow velocity. Conclusions In a sample of blacks, higher aortic stiffness and pressure pulsatility were associated with lower flow reserve during reactive hyperemia, beyond changes attributable to traditional cardiovascular disease risk factors alone.

13.
BMC Nephrol ; 19(1): 239, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30236068

RESUMO

BACKGROUND: Few investigations have evaluated the incremental usefulness of multiple biomarkers representing varying physiological pathways for predicting risk of renal outcomes in African Americans. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We related a multi-marker panel to incident chronic kidney disease (CKD) and rapid kidney function decline (RKFD) in 2813 Jackson Heart Study participants without prevalent CKD at exam 1 (2000-2004) and with complete assays at exam 1 for 9 biomarkers: adiponectin, aldosterone, B-natriuretic peptide [BNP], cortisol, high sensitivity C-reactive protein (hsCRP), endothelin, homocysteine, plasma renin activity and mass. Incident CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at exam 3 while RKFD was defined as eGFR ≥30% loss between exams 1 and 3 (8.2 median years). We employed multiple logistic regression model to describe association between the panel and incident CKD and RKFD and used backward elimination strategy to estimate the most parsimonious biomarker model while controlling for conventional risk factors. RESULTS: The multi-marker panel predicted the risk for both incident CKD (odds ratios [OR], 2.72; 95% confidence intervals [CI], 1.63, 4.56; P = 0.001) and RKFD (2.61; 95% CI, 1.67, 4.08; P < 0.001). Per standard deviation increase in log biomarker concentrations were significantly (multivariable adjusted odds ratios, [95% confidence interval], p-value) associated with incident CKD: plasma adiponectin (1.24 [1.07, 1.44], p = 0.005) and leptin (1.3 [1.06, 1.61], p = 0.011), and with RKFD: plasma adiponectin (1.22 [1.06, 1.40], p = 0.006); hsCRP (1.17 [1.01, 1.36], p = 0.031) and aldosterone (0.85 [0.74, 0.96], p = 0.012). Moderate levels (3rd quartile) of aldosterone were inversely associated with incident CKD (0.54 [0.35, 0.82], p = 0.004) while leptin was associated with RKFD (1.64 [1.10, 2.44], p = 0.015). Biomarkers improved CKD risk prediction (P = 0.003) but not RKFD risk prediction (P = 0.10). CONCLUSION: In this community-based sample of African Americans, a multi-marker panel added only moderate predictive improvement compared to conventional risk factors.

14.
Basic Res Cardiol ; 113(5): 40, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30132266

RESUMO

Sex differences in heart failure development following myocardial infarction (MI) are not fully understood. We hypothesized that differential MI signaling could explain variations in outcomes. Analysis of the mouse heart attack research tool 1.0 (422 mice; young = 5.4 ± 0.1; old = 23.3 ± 0.1 months of age) was used to dissect MI signaling pathways, which was validated in a new cohort of mice (4.8 ± 0.2 months of age); and substantiated in humans. Plasma collected at visit 2 from the MI subset of the Jackson Heart Study (JHS; a community-based study consisting of middle aged and older adults of African ancestry) underwent glycoproteomics grouped by outcome: (1) heart failure hospitalization after visit 2 (n = 3 men/12 women) and (2) without hospitalization through 2012 (n = 24 men/21 women). Compared to young male mice, the infarct region of young females had fewer, but more efficient tissue clearing neutrophils with reduced pro-inflammatory gene expression. Apolipoprotein (Apo) F, which acts upstream of the liver X receptors/retinoid X receptor (LXR/RXR) pathway, was elevated in the day 7 infarcts of old mice compared to young controls and was increased in both men and women with heart failure. In vitro, Apo F stimulated CD36 and peroxisome proliferator-activated receptor (PPAR)γ activation in male neutrophils to turn off NF-κB activation and stimulate LXR/RXR signaling to initiate resolution. Female neutrophils were desensitized to Apo F and instead relied on thrombospondin-1 stimulation of CD36 to upregulate AMP-activated protein kinase, resulting in an overall better wound healing strategy. With age, female mice were desensitized to LXR/RXR signaling, resulting in enhanced interleukin-6 activation, a finding replicated in the JHS community cohort. This is the first report to uncover sex differences in post-MI neutrophil signaling that yielded better outcomes in young females and worse outcomes with age.

15.
PLoS One ; 13(6): e0198166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29912962

RESUMO

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

16.
Diabetol Metab Syndr ; 10: 42, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29796112

RESUMO

Background: The severity of the metabolic syndrome (MetS) predicts future coronary heart disease (CHD) and diabetes independent of the individual MetS components. Our aim was to evaluate whether MetS severity conferred additional discrimination to existing scoring systems for cardiovascular disease (CVD) and diabetes risk. Methods: We assessed Cox proportional hazard models of CHD- and diabetes risk among 13,141 participants of the Atherosclerosis Risk in Communities Study and the Jackson Heart Study, using the Framingham Risk Calculator, the American Heart Association's Atherosclerotic CVD calculator, the American Diabetes Association diabetes risk score and an additional diabetes risk score derived from ARIC data. We then added a MetS-severity Z-score to these models and assessed for added risk discrimination by assessing Akaike information criterion, c-statistic, integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI). Results: The MetS severity score appears to add to the predictive ability of individual CHD and diabetes risk scores. Using the IDI, MetS improved risk prediction for diabetes but not CHD risk. In all 4 scoring systems, MetS severity had a significant non-event NRI, improving the ability to exclude individuals without events. Assessing interactions between risk scores and MetS severity revealed that MetS severity was more highly associated with disease risk among those in the lowest quintiles of risk score, suggesting that MetS was particularly able to identify risk among individuals judged to be of low risk by existing algorithms. Conclusions: Mets severity improved prediction of diabetes more so than CHD. Incorporation of multiple risk predictors into electronic health records may help in better identifying those at high disease risk, who can then be placed earlier on preventative therapy.

18.
Kidney Blood Press Res ; 43(2): 555-567, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29642060

RESUMO

BACKGROUND/AIMS: The metabolic syndrome (MetS), as assessed using dichotomous criteria, is associated with increased risk of future chronic kidney disease (CKD), though this relationship is unclear among African Americans, who have lower risk for MetS but higher risk for CKD. METHODS: We performed logistic regression using a sex- and race-specific MetS-severity z-score to assess risk of incident CKD among 2,627 African-American participants of the Jackson Heart Study, assessed at baseline and 8 years later. Based on quartile of baseline MetS severity, we further assessed prevalence of being in the lowest quartile of baseline GFR, the lowest quartile of relative GFR at follow-up, microalbuminuria and incident CKD. RESULTS: Higher MetS-severity was associated with higher prevalence of GFR in the lowest quartile at baseline among males and females. Among African-American females but not males, higher baseline MetS-severity was associated with a higher prevalence of baseline elevations in microabuminuria (p<0.01), steep decline in GFR (p<0.001) and a higher incidence of CKD (p<0.0001). Women in increasing quartiles of baseline MetS-severity exhibited a linear trend toward higher odds of future CKD (p<0.05), with those in the 4th quartile of MetS-severity (compared to the 1st) having an odds ratio of 2.47 (95% confidence interval 1.13, 5.37); no such relationship was seen among men (p value for trend 0.49). CONCLUSION: MetS-severity exhibited sex-based interactions regarding risk for future GFR deterioration and CKD, with increasing risk in women but not men. These data may have implications for triggering CKD screening among African-American women with higher degrees of MetS-severity.


Assuntos
Taxa de Filtração Glomerular , Síndrome Metabólica/diagnóstico , Insuficiência Renal Crônica/etiologia , Índice de Gravidade de Doença , Adulto , Afro-Americanos , Idoso , Albuminúria , Grupos de Populações Continentais , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/etnologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etnologia , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologia
19.
Psychoneuroendocrinology ; 90: 141-147, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29494952

RESUMO

INTRODUCTION: Using Jackson Heart Study (JHS) data, we assessed the association between perceived psychosocial stressors and metabolic syndrome (MetS) severity in African American adults. METHODS: Participants included 3870 African American JHS participants aged 21-95 years (63.1% women; mean age 53.8 ±â€¯13.0). Psychosocial stressors assessed included: major life events (MLEs); global stress; and weekly stress inventory. Each stress measure was classified into tertiles (low, medium, and high). Associations of psychosocial stressors with a sex- and race/ethnic-specific MetS severity Z-score were examined after adjustment for demographics and MetS risk factors (i.e., nutrition, physical activity, smoking status, and alcohol consumption). RESULTS: Independent of lifestyle factors, participants who reported high (versus low) perceived global stress and MLEs had significantly greater MetS severity (p = .0207 and p = .0105, respectively). Weekly stress was not associated with MetS severity. Compared to men, women reported significantly higher global stress and MLEs (p < 0.0001). A significant interaction between sex and MLEs (p = .0456) demonstrated men significantly increased their MetS severity at medium levels of stress, whereas women's MetS severity was significantly increased at high levels of MLEs. CONCLUSIONS: In the total sample, higher reported global stress and MLEs were associated with increased risk of MetS severity, while weekly stress was not. Men's and women's stress responses to MLEs were differentially associated with MetS severity, with male MetS severity increasing significantly at lower levels of MLEs relative to women's MetS severity. These data may have implications for targeting stress-related factors in interventions to improve cardiometabolic health in African American adults.

20.
Metabolism ; 83: 68-74, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29410278

RESUMO

BACKGROUND: Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease. METHODS: To formulate the MetS-Z-BMI, we performed confirmatory factor analysis on a sex- and race/ethnicity-specific basis on MetS-related data for 6870 adult participants of the National Health and Nutrition Survey 1999-2010. We then validated this score and compared it to MetS-Z-WC in assessing correlations with future coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM) using Cox proportional hazard analysis of 13,094 participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study. RESULTS: Loading factors, which represent the relative contribution of each component to the latent MetS factor, were lower for BMI than for WC in formulating the two respective scores (MetS-Z-BMI and MetS-Z-WC). Nevertheless, MetS-Z-BMI and MetS-Z-WC exhibited similar hazard ratios (HR) toward future disease. For each one standard-deviation-unit increase in MetS-Z-BMI, HR for CHD was 1.76 (95% confidence interval [CI]: 1.65, 1.88) and HR for T2DM was 3.39 (CI 3.16, 3.63) (both p < 0.0001). There were no meaningful differences between the MetS-Z-WC and MetS-Z-BMI scores in their associations with future CHD and T2DM. CONCLUSIONS: A MetS severity Z-score utilizing BMI as its measure of adiposity operated similarly to a WC-based score in predicting future CHD and T2DM, suggesting overall similarity in MetS-based risk as estimated by both measures of adiposity. This indicates potential clinical usefulness of MetS-Z-BMI in assessing and following MetS-related risk over time.

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