RESUMO
Protease-activated receptor 4 (PAR4) (gene F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency is more common in Black individuals, and Black individuals have a higher incidence of ischemic stroke than White individuals. However, it is not known whether the A allele is responsible for worse stroke outcomes. To directly test the in vivo effect of this variant on stroke, we generated mice in which F2rl3 was replaced by F2RL3, thereby expressing human PAR4 (hPAR4) with either Thr120 or Ala120. Compared with hPAR4 Ala120 mice, hPAR4 Thr120 mice had worse stroke outcomes, mediated in part by enhanced platelet activation and platelet-neutrophil interactions. Analyses of 7,620 Black subjects with 487 incident ischemic strokes demonstrated the AA genotype was a risk for incident ischemic stroke and worse functional outcomes. In humanized mice, ticagrelor with or without aspirin improved stroke outcomes in hPAR4 Ala120 mice, but not in hPAR4 Thr120 mice. P selectin blockade improved stroke outcomes and reduced platelet-neutrophil interactions in hPAR4 Thr120 mice. Our results may explain some of the racial disparity in stroke and support the need for studies of nonstandard antiplatelet therapies for patients expressing PAR4 Thr120.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Animais , Camundongos , Receptores de Trombina/genética , Agregação Plaquetária/genética , Plaquetas/fisiologia , Inibidores da Agregação Plaquetária/farmacologia , Acidente Vascular Cerebral/genética , Receptor PAR-1RESUMO
BACKGROUND: Prior studies have identified an association between hypertension and hyperuricemia; however, there has been limited research on the association between hypertension severity and hyperuricemia. METHOD: We studied 997 Black and white adults with serum urate data from the reasons for geographic and racial differences in stroke (REGARDS) study. Hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg or self-reported use of antihypertensive medication. Apparent treatment-resistant hypertension (aTRH) was defined as a SBP ≥ 140 mmHg or DBP ≥ 90 mmHg with concurrent use of three classes of antihypertensive medications, or taking four or more classes of antihypertensive medication regardless of BP level. Controlled BP was defined as SBP <140 mmHg and DBP <90 mmHg. RESULTS: Overall 5.9% of participants had aTRH and 36.6% had hyperuricemia, defined as serum urate >7.0 mg/dl for men and >6.0 mg/dl for women. After full multivariable adjustment, the odds ratio (OR) for hyperuricemia associated with hypertension was 1.60 [95% confidence interval (95% CI): 1.06-2.40]. Compared to participants not taking antihypertensive medication, the ORs for hyperuricemia for participants taking one, two and three classes of antihypertensive medication without aTRH were 1.98 (95% CI: 1.23-3.20), 2.08 (95% CI: 1.25-3.43), 4.31 (95% CI: 2.07-8.97), respectively, and 3.96 (95% CI: 1.75-8.96) for aTRH. Compared to participants without hypertension, the odds ratios for hyperuricemia were 1.67 (95% CI: 1.08-2.58) and 1.46 (95% CI: 0.88-2.44) among those with hypertension with and without controlled BP, respectively. Diuretic use was associated with a higher odds of hyperuricemia. CONCLUSION: This study suggests that individuals taking more classes of antihypertensive medication may benefit from monitoring for hyperuricemia.
Assuntos
Hipertensão , Hiperuricemia , Acidente Vascular Cerebral , Masculino , Adulto , Humanos , Feminino , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Hiperuricemia/complicações , Hiperuricemia/tratamento farmacológico , Ácido Úrico , Fatores Raciais , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Pressão SanguíneaRESUMO
Introduction: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data. Methods: Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP (n = 1,705). A normotensive control group was defined as individuals with BP < 140/90 mmHg (n = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP < 140/ 90 mmHg (n = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American). Results: One variant in the known HTN locus, KCNK3, was a top finding in the multi-ethnic analysis (p = 8.23E-07) for the normotensive control group [rs12476527, odds ratio (95% confidence interval) = 0.80 (0.74-0.88)]. This variant was replicated in the Vanderbilt University Medical Center's DNA repository data. Aggregate gene-based signals included the genes AGTPBP, MYL4, PDCD4, BBS9, ERG, and IER3. Discussion: Additional work validating these loci in larger, more diverse populations, is warranted to determine whether these regions influence the pathobiology of aTRH.
RESUMO
Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in BP response to antihypertensive treatment, suggesting a genetic component. Utilizing data from 4297 AA participants randomized to chlorthalidone from the Genetics of Hypertension Associated Treatments (GenHAT) study, we aimed to identify variants associated with the efficacy of chlorthalidone. An additional aim was to find variants that contributed to changes in fasting glucose (FG) in these individuals. We performed genome-wide association analyses on the change of systolic and diastolic BP (SBP and DBP) over six months and FG levels over 24 months of treatment. We sought replication in the International Consortia of Pharmacogenomics Studies. We identified eight variants statistically associated with BP response and nine variants associated with FG response. One suggestive LINC02211-CDH9 intergenic variant was marginally replicated with the same direction of effect. Given the impact of hypertension in AAs, this study implies that understanding the genetic background for BP control and glucose changes during chlorthalidone treatment may help prevent adverse cardiovascular events in this population.
Assuntos
Clortalidona , Hipertensão , Negro ou Afro-Americano/genética , Clortalidona/efeitos adversos , Estudo de Associação Genômica Ampla , Glucose , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Estados UnidosRESUMO
Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10-8/132 = 4 × 10-10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p < 8.0 × 10-7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10-3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal.
Assuntos
Genômica , Hipolipemiantes/farmacologia , Lipidômica , Período Pós-Prandial/efeitos dos fármacos , Período Pós-Prandial/genética , Adulto , Idoso , Dessaturase de Ácido Graxo Delta-5/genética , Ácidos Graxos Dessaturases/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Lipídeos , Masculino , Refeições , Pessoa de Meia-Idade , Fenótipo , Plasma , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The American Heart Association created the Life's Simple 7 (LS7) metrics to promote cardiovascular health (CVH) by achieving optimal levels of blood pressure, cholesterol, blood sugar, physical activity, diet, weight, and smoking status. The degree to which psychosocial factors such as stress and depression impact one's ability to achieve optimal CVH is unclear, particularly among hypertensive African Americans. METHODS: Cross-sectional analyses included 1,819 African Americans with hypertension participating in the Jackson Heart Study (2000-2004). Outcomes were LS7 composite and individual component scores (defined as poor, intermediate, ideal). High perceived chronic stress was defined as the top quartile of Weekly Stress Inventory scores. High depressive symptoms were defined as Center for Epidemiologic Studies Depression scale scores of ≥16. We compared 4 groups: high stress alone; high depressive symptoms alone; high stress and high depressive symptoms; low stress and low depressive symptoms (reference) using linear regression for total LS7 scores and logistic regression for LS7 components. RESULTS: Participants with both high stress and depressive symptoms had lower composite LS7 scores (B [95% confidence interval] = -0.34 [-0.65 to -0.02]) than those with low stress and depressive symptoms in unadjusted and age/sex-adjusted models. They also had poorer health status for smoking (odds ratio [95% confidence interval] = 0.52 [0.35-0.78]) and physical activity (odds ratio [95% confidence interval] = 0.71 [0.52-0.95]) after full covariate adjustment. CONCLUSIONS: The combination of high stress and high depressive symptoms was associated with poorer LS7 metrics in hypertensive African Americans. Psychosocial interventions may increase the likelihood of engaging in behaviors that promote optimal CVH.
Assuntos
Doenças Cardiovasculares , Hipertensão , Negro ou Afro-Americano , Pressão Sanguínea , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Estudos Longitudinais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals. Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs aiming to evaluate cross-ethnic performance. Results: We identified 10 statistically significant (p < 5.00E-08) and 90 additional suggestive (p < 1.00E-06) variants associated with incident stroke in the meta-analysis. Six of the top 10 variants were located in an intergenic region on chromosome 18 (LINC01443-LOC644669). Additional variants of interest were located in or near the COL12A1, SNTG1, PCDH7, TMTC1, and NTM genes. Replication was conducted in the Warfarin Pharmacogenomics Cohort (WPC), and while none of the variants were directly validated, seven intronic variants of NTM proximal to our target variants, had a p-value <5.00E-04 in the WPC. The inclusion of the PRS did not improve the prediction accuracy compared to a reference model adjusting for age, sex, and genetic ancestry in either study and had lower predictive accuracy compared to models accounting for established stroke risk factors. These results demonstrate the necessity for PRS derivation in AAs, particularly for diseases that affect AAs disproportionately. Conclusion: This study highlights biologically plausible genetic determinants for incident stroke in hypertensive AAs. Ultimately, a better understanding of genetic risk factors for stroke in AAs may give new insight into stroke burden and potential clinical tools for those among the highest at risk.
RESUMO
BACKGROUND: Guidelines recommend adults who discontinue statin therapy because of statin-associated symptoms be reinitiated. Low-density lipoprotein cholesterol (LDL-C) levels achieved after statin reinitiation are unknown. OBJECTIVE: The objective of this study was to determine LDL-C levels after statin reinitiation. METHODS: We analyzed data from 5498 participants in the REasons for Geographic And Racial Differences in Stroke study who reported ever taking a statin. We categorized participants according to their pattern of statin use including those taking a statin who did not experience statin-associated symptoms and continued treatment, and those who discontinued statins because of statin-associated symptoms and were not reinitiated, reinitiated and remained on treatment, and discontinued treatment after being reinitiated. Mortality and vascular event reduction with statin reinitiation was estimated using data from the Cholesterol-Lowering Treatment Trialists Collaboration. RESULTS: After multivariable adjustment, LDL-C was 14.1 (95% CI: 9.9-18.3) mg/dL higher among participants reinitiated and taking a statin compared with those without statin-associated symptoms who continued statin therapy. Mean LDL-C was 18.1 mg/dL (95% CI: 13.0-23.1) and 27.5 mg/dL (95% CI: 20.7-34.4) lower among participants reinitiated and taking a statin compared with those who discontinued statin therapy and were not reinitiated and those who discontinued statins after being reinitiated, respectively. An LDL-C reduction of 18.1 mg/dL with statin reinitiation was projected to reduce all-cause and coronary heart disease mortality by 5.6% and 8.9%, respectively, and myocardial infarction or coronary heart disease death and major vascular events by 10.7% and 9.8%, respectively, over 5 years. CONCLUSION: Reinitiating individuals who discontinue statin therapy may reduce LDL-C and cardiovascular risk.
Assuntos
LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Infarto do Miocárdio/sangue , Retratamento , Acidente Vascular Cerebral/sangueRESUMO
Objectives. To determine factors that explain the higher Black:White cardiovascular disease (CVD) mortality rates among US adults.Methods. We analyzed data from the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2017 to estimate Black:White hazard ratios (HRs) for CVD mortality within subgroups younger than 65 years and aged 65 years or older.Results. Among 29 054 participants, 41.0% who were Black and 54.9% who were women, 1549 CVD deaths occurred. Among participants younger than 65 years, the demographic-adjusted Black:White CVD mortality HR was 2.23 (95% confidence interval [CI] = 1.87, 2.65) and 1.21 (95% CI = 1.00, 1.47) after full adjustment. Among participants aged 65 years or older, the demographic-adjusted Black:White CVD mortality HR was 1.58 (95% CI = 1.39, 1.79) and 1.12 (95% CI = 0.97, 1.29) after full adjustment. When we used mediation analysis, socioeconomic status explained 21.2% (95% CI = 13.6%, 31.4%) and 38.0% (95% CI = 20.9%, 61.7%) of the Black:White CVD mortality risk difference among participants younger than 65 years and aged 65 years or older, respectively. CVD risk factors explained 56.6% (95% CI = 42.0%, 77.2%) and 41.3% (95% CI = 22.9%, 65.3%) of the Black:White CVD mortality difference for participants younger than 65 years and aged 65 years or older, respectively.Conclusions. The higher Black:White CVD mortality risk is primarily explained by racial differences in socioeconomic status and CVD risk factors.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Doenças Cardiovasculares/etnologia , População Branca/estatística & dados numéricos , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/mortalidade , Comorbidade , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVES: Recent guidelines recommend out-of-clinic BP measurements. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared the prevalence of BP phenotypes between 561 black patients, with and without CKD, taking antihypertensive medication who underwent ambulatory BP monitoring at baseline (between 2000 and 2004) in the Jackson Heart Study. CKD was defined as an albumin-to-creatinine ratio ≥30 mg/g or eGFR <60 ml/min per 1.73 m2. Sustained controlled BP was defined by BP at goal both inside and outside of the clinic and sustained uncontrolled BP as BP above goal both inside and outside of the clinic. Masked uncontrolled hypertension was defined by controlled clinic-measured BP with uncontrolled out-of-clinic BP. RESULTS: CKD was associated with a higher multivariable-adjusted prevalence ratio for uncontrolled versus controlled clinic BP (prevalence ratio, 1.44; 95% CI, 1.02 to 2.02) and sustained uncontrolled BP versus sustained controlled BP (prevalence ratio, 1.66; 95% CI, 1.16 to 2.36). There were no statistically significant differences in the prevalence of uncontrolled daytime or nighttime BP, nondipping BP, white-coat effect, and masked uncontrolled hypertension between participants with and without CKD after multivariable adjustment. After multivariable adjustment, reduced eGFR was associated with masked uncontrolled hypertension versus sustained controlled BP (prevalence ratio, 1.42; 95% CI, 1.00 to 2.00), whereas albuminuria was associated with uncontrolled clinic BP (prevalence ratio, 1.76; 95% CI, 1.20 to 2.60) and sustained uncontrolled BP versus sustained controlled BP (prevalence ratio, 2.02; 95% CI, 1.36 to 2.99). CONCLUSIONS: The prevalence of BP phenotypes defined using ambulatory BP monitoring is high among adults with CKD taking antihypertensive medication.
Assuntos
Anti-Hipertensivos/uso terapêutico , Negro ou Afro-Americano , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Rim/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Albuminúria/diagnóstico , Albuminúria/etnologia , Albuminúria/fisiopatologia , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/etnologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Fenótipo , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etnologia , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Recent studies have suggested that prediabetes is associated with an increased risk for cardiovascular disease (CVD) only among individuals with concomitant hypertension. RESEARCH DESIGN AND METHODS: We analyzed the association between prediabetes and CVD by hypertension status among 3,313 black adults in the Jackson Heart Study (JHS) without diabetes or a history of CVD at baseline (2000-2004). Prediabetes was defined as fasting plasma glucose between 100 and 125 mg/dL or hemoglobin A1c between 5.7 and 6.4% (39 and 46 mmol/mol). Hypertension was defined as systolic/diastolic blood pressure ≥140/90 mmHg and/or self-reported antihypertensive medication use. Participants were followed for incident CVD events and all-cause mortality through 31 December 2014. RESULTS: Overall, 35% of JHS participants did not have prediabetes or hypertension, 18% had prediabetes alone, 22% had hypertension alone, and 25% had both prediabetes and hypertension. Compared with participants without either condition, the multivariable-adjusted hazard ratios for CVD events among participants with prediabetes alone, hypertension alone, and both prediabetes and hypertension were 0.86 (95% CI 0.51, 1.45), 2.09 (1.39, 3.14), and 1.93 (1.28, 2.90), respectively. Among participants with and without hypertension, there was no association between prediabetes and an increased risk for CVD (0.78 [0.46, 1.34] and 0.94 [0.70, 1.26], respectively). No association was present between prediabetes and all-cause mortality among participants with or without hypertension. CONCLUSIONS: Regardless of hypertension status, prediabetes was not associated with an increased risk for CVD or all-cause mortality in this cohort of black adults.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Doenças Cardiovasculares/etiologia , Hipertensão/epidemiologia , Estado Pré-Diabético/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipertensão/etiologia , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described. METHODS: We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (<140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL. RESULTS: The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 × 10-8) and in the race-combined analysis (P = 1.5 × 10-9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95% confidence interval: 0.6-0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls. CONCLUSION: This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/genética , Proteínas de Ligação a DNA/genética , Resistência a Medicamentos/genética , Hipertensão/tratamento farmacológico , Hipertensão/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Negro ou Afro-Americano/genética , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Proteínas Associadas à Distrofina/genética , Europa (Continente)/epidemiologia , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/etnologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética , Neuropeptídeos/genética , Farmacogenética , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia , População Branca/genéticaRESUMO
Importance: Little is known regarding health outcomes associated with higher blood pressure (BP) levels measured outside the clinic among African American individuals. Objective: To examine whether daytime and nighttime BP levels measured outside the clinic among African American individuals are associated with cardiovascular disease (CVD) and all-cause mortality independent of BP levels measured inside the clinic. Design, Setting, and Participants: This prospective cohort study analyzed data from 1034 African American participants in the Jackson Heart Study who completed ambulatory BP monitoring at baseline (September 26, 2000, to March 31, 2004). Mean daytime and nighttime BPs were calculated based on measurements taken while participants were awake and asleep, respectively. Data were analyzed from July 1, 2017, to April 30, 2019. Main Outcomes and Measures: Cardiovascular disease events, including coronary heart disease and stroke, experienced through December 31, 2014, and all-cause mortality experienced through December 31, 2016, were adjudicated. The associations of daytime BP and nighttime BP, separately, with CVD events and all-cause mortality were determined using Cox proportional hazards regression models. Results: A total of 1034 participants (mean [SD] age, 58.9 [10.9] years; 337 [32.6%] male; and 583 [56.4%] taking antihypertensive medication) were included in the study. The mean daytime systolic BP (SBP)/diastolic BP (DBP) was 129.4/77.6 mm Hg, and the mean nighttime SBP/DBP was 121.3/68.4 mm Hg. During follow-up (median [interquartile range], 12.5 [11.1-13.6] years for CVD and 14.8 [13.7-15.6] years for all-cause mortality), 113 CVD events and 194 deaths occurred. After multivariable adjustment, including in-clinic SBP and DBP, the hazard ratios (HRs) for CVD events for each SD higher level were 1.53 (95% CI, 1.24-1.88) for daytime SBP (per 13.5 mm Hg), 1.48 (95% CI, 1.22-1.80) for nighttime SBP (per 15.5 mm Hg), 1.25 (95% CI, 1.02-1.51) for daytime DBP (per 9.3 mm Hg), and 1.30 (95% CI, 1.06-1.59) for nighttime DBP (per 9.5 mm Hg). Nighttime SBP was associated with all-cause mortality (HR per 1-SD higher level, 1.24; 95% CI, 1.06-1.45), but no association was present for daytime SBP (HR, 1.13; 95% CI, 0.97-1.33) and daytime (HR, 0.95; 95% CI, 0.81-1.10) and nighttime (HR, 1.06; 95% CI, 0.90-1.24) DBP. Conclusions and Relevance: Among African American individuals, higher daytime and nighttime SBPs were associated with an increased risk for CVD events and all-cause mortality independent of BP levels measured in the clinic. Measurement of daytime and nighttime BP using ambulatory monitoring during a 24-hour period may help identify African American individuals who have an increased cardiovascular disease risk.
Assuntos
Negro ou Afro-Americano , Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Ritmo Circadiano/fisiologia , Pacientes Ambulatoriais , Adulto , Doenças Cardiovasculares/etnologia , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Background Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular disease (CVD) events and all-cause mortality. Many individuals without LVH have a left ventricular mass that exceeds the level predicted by their sex, body size, and cardiac workload, a condition called inappropriate left ventricular mass (iLVM). We investigated the association of iLVM with CVD events and all-cause mortality among blacks. Methods and Results We analyzed data from the Jackson Heart Study, a community-based cohort of blacks. The current analysis included 4424 participants without CVD and with an echocardiogram at baseline. Among this cohort, the prevalence of iLVM was 13.8%. There were 262 CVD events and 419 deaths over a median follow-up of 9.7 years (maximum, 12 years). Compared with participants without iLVM, participants with iLVM had a higher rate of CVD events and all-cause mortality. After multivariable adjustment, including for the presence of LVH, iLVM was associated with an increased risk of CVD events (hazard ratio, 1.87; 95% CI, 1.33-2.62). The multivariable-adjusted hazard ratio for all-cause mortality was 1.29 (95% CI, 0.98-1.70). Among participants without and with LVH, the multivariable-adjusted hazard ratios of iLVM for CVD events were 2.53 (95% CI, 1.68-3.81) and 1.21 (95% CI, 0.74-2.00), respectively (Pinteraction=0.029); and for all-cause mortality, the hazard ratios were 1.24 (95% CI, 0.81-1.89) and 1.26 (95% CI, 0.86-1.85), respectively (Pinteraction=0.664). Conclusions iLVM is associated with an increased risk for CVD events among blacks without LVH.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Mortalidade , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Causas de Morte , Estudos de Coortes , Ecocardiografia , Feminino , Ventrículos do Coração/patologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tamanho do Órgão , Modelos de Riscos Proporcionais , Volume Sistólico , Estados Unidos/epidemiologiaRESUMO
Background The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recognize cardiovascular disease and diabetes mellitus but not chronic kidney disease ( CKD ) as high-risk conditions warranting statin therapy. Statin use may be lower for adults with CKD compared with adults with conditions that have guideline indications for statin use. Methods and Results We analyzed data from the National Health and Nutrition Examination Surveys from 1999-2002 through 2011-2014 to determine trends in the percentage of US adults ≥20 years of age with and without CKD taking statins. CKD was defined by an estimated glomerular filtration rate <60 mL/min per 1.73m2 or albumin-to-creatinine ratio ≥30 mg/g. Statin use was identified through a medication inventory. Between 1999-2002 and 2011-2014, the percentage of adults taking statins increased from 17.6% to 35.7% among those with CKD and from 6.8% to 14.7% among those without CKD . After multivariable adjustment, adults with CKD were not more likely to be taking statins compared with those without CKD (prevalence ratio, 1.01; 95% CI] 0.96-1.08). Among adults without a history of cardiovascular disease, those with CKD but not diabetes mellitus were less likely to be taking statins compared with those with diabetes mellitus but not CKD (prevalence ratio, 0.54; 95% CI , 0.44-0.66). Among adults with a history of cardiovascular disease, there was no difference in statin use between those with CKD but not diabetes mellitus versus those with diabetes mellitus but not CKD (prevalence ratio, 0.95; 95% CI , 0.79-1.15). Conclusions CKD does not appear to be a major stimulus for statin use among US adults.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Previsões , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inquéritos Nutricionais , Insuficiência Renal Crônica/complicações , Adulto , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Blacks have a high prevalence of hypertension and uncontrolled blood pressure (BP), each of which may be partially explained by untreated sleep apnea. We investigated the association of sleep apnea with uncontrolled BP and resistant hypertension in blacks. METHODS: Between 2012 and 2016, Jackson Heart Sleep Study participants (N=913) underwent an in-home Type 3 sleep apnea study, clinic BP measurements, and anthropometry. Moderate or severe obstructive sleep apnea (OSA) was defined as a respiratory event index ≥15, and nocturnal hypoxemia was quantified as percent sleep time with <90% oxyhemoglobin saturation. Prevalent hypertension was defined as either a systolic BP ≥130 mm Hg or diastolic BP >80mm Hg, use of antihypertensive medication, or self-report of a diagnosis of hypertension. Controlled BP was defined as systolic BP <130 mm Hg and diastolic BP <80 mm Hg; uncontrolled BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with use of 1 to 2 classes of antihypertensive medication; and resistant BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with the use of ≥3 classes of antihypertensive medication (including a diuretic) or use of ≥4 classes of antihypertensive medication regardless of BP level. Multinomial logistic regression models were fit to determine the association between OSA severity and uncontrolled BP or resistant hypertension (versus controlled BP) after multivariable adjustment. RESULTS: The analytic sample with hypertension (N=664) had a mean age of 64.0 (SD,10.6) years, and were predominately female (69.1%), obese (58.6%), and college educated (51.3%). Among the sample, 25.7% had OSA, which was untreated in 94% of participants. Overall, 48% of participants had uncontrolled hypertension and 14% had resistant hypertension. After adjustment for confounders, participants with moderate or severe OSA had a 2.0 times higher odds of resistant hypertension (95% confidence interval [CI], 1.14-3.67). Each standard deviation higher than <90% oxyhemoglobin saturation was associated with an adjusted odds ratio for resistant hypertension of 1.25 (95% CI 1.01-1.55). OSA and <90% oxyhemoglobin saturation were not associated with uncontrolled BP. CONCLUSION: Untreated moderate or severe OSA is associated with increased odds of resistant hypertension. These results suggest that untreated OSA may contribute to inadequate BP control in blacks.
Assuntos
Negro ou Afro-Americano , Pressão Sanguínea , Hipertensão/etnologia , Síndromes da Apneia do Sono/etnologia , Sono , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Estudos Transversais , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns. METHODS: Our study included 973 African American adults enrolled in the Jackson Heart Study (2000-2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire as follows: (i) absolute daily intake, (ii) ratio of phosphorus-to-protein intake, (iii) phosphorus density, and (iv) energy-adjusted phosphorus intake. Using multivariable linear regression, we determined associations between dietary phosphorus intake and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure in clinic and over daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping was also assessed. Using logistic regression, we modeled relationships between dietary phosphorus intake and clinically relevant qualitative BP phenotypes, such as masked, sustained, or white-coat hypertension and normotension. RESULTS: There were no statistically significant associations between phosphorus intake and SBP or pulse pressure in adjusted models. Most metrics of higher phosphorus intake were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus intake was not associated with clinic or ABPM-defined hypertension overall, but most metrics of higher phosphorus intake were associated with lower odds of sustained hypertension compared to sustained normotension, white-coat hypertension, and masked hypertension. There were no associations between dietary phosphorus and nocturnal BP dipping. CONCLUSIONS: These data do not support a role for higher phosphorus intake and higher BP in African Americans.
Assuntos
Negro ou Afro-Americano , Pressão Sanguínea , Hipertensão/etnologia , Fósforo na Dieta/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
Guidelines recommend attempting to reinitiate statins in patients who discontinue treatment. Previous experiences while taking a statin, including side effects, may reduce a patient's willingness to reinitiate treatment. We determined the percentage of adults who are willing to reinitiate statin therapy after treatment discontinuation. Factors associated with willingness to reinitiate a statin were also examined. A statin questionnaire was administered and study examination conducted in black and white US adults enrolled in the nationwide REasons for Geographic And Racial Differences in Stroke study from 2013 to 2017. In participants who self-reported ever having taken a statin (nâ¯=â¯7,216, mean age 72 years, 53% women, 34% black), 1,081 (15%) reported having discontinued treatment. Among those who discontinued treatment, statin side effects, perceived lack of need for a statin, and cost were reported by 66%, 31%, and 3% of participants, respectively. Overall, 37% of participants who had discontinued treatment were willing to reinitiate statin therapy. Participants who discontinued treatment due to cost (prevalence ratio [PR] 1.61; 95% confidence interval (CI) 1.01, 2.57) were more likely to report a willingness to reinitiate therapy. Participants with a low-density lipoprotein-cholesterol ≥130 mg/dl versus <100 mg/dl (PR 0.69; 95% CI 0.53, 0. 88) and who discontinued treatment due to side effects (PR 0.51; 95% CI 0.41, 0.64) were less likely to report willingness to reinitiate statin therapy. In conclusion, a substantial proportion of participants who discontinued statin therapy were willing to reinitiate treatment. Healthcare providers should discuss reinitiation of statin therapy with their patients who have discontinued treatment.