Harsha S. Nagarajarao

The relation of C - reactive protein to chronic kidney disease in African Americans: the Jackson Heart Study

BackgroundAfrican Americans have an increased incidence and worse prognosis with chronic kidney disease (CKD - estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) than their counterparts of European-descent. Inflammation has been related to renal disease in non-Hispanic whites, but there are limited data on the role of inflammation in renal dysfunction in African Americans in the community.MethodsWe examined the cross-sectional relation of log transformed C-reactive protein (CRP) to renal function (eGFR by Modification of Diet and Renal Disease equation) in African American participants of the community-based Jackson Heart Studys first examination (2000 to 2004). We conducted multivariable linear regression relating CRP to eGFR adjusting for age, sex, body mass index, systolic and diastolic blood pressure, diabetes, total/HDL cholesterol, triglycerides, smoking, antihypertensive therapy, lipid lowering therapy, hormone replacement therapy, and prevalent cardiovascular disease events. In a secondary analysis we assessed the association of CRP with albuminuria (defined as albumin-to-creatinine ratio > 30 mg/g).ResultsParticipants (n = 4320, 63.2% women) had a mean age ± SD of 54.0 ± 12.8 years. The prevalence of CKD was 5.2% (n = 228 cases). In multivariable regression, CRP concentrations were higher in those with CKD compared to those without CKD (mean CRP 3.2 ± 1.1 mg/L vs. 2.4 ± 1.0 mg/L, respectively p < 0.0001). CRP was significantly associated with albuminuria in sex and age adjusted model however not in the multivariable adjusted model (p > 0.05).ConclusionCRP was associated with CKD however not albuminuria in multivariable-adjusted analyses. The study of inflammation in the progression of renal disease in African Americans merits further investigation.

The Predictive Value of Left Atrial Size for Incident Ischemic Stroke and All-Cause Mortality in African Americans. The Atherosclerosis Risk in Communities (ARIC) Study

Background and Purpose— The association between left atrial (LA) size, ischemic stroke, and death has not been well established in African Americans despite their disproportionately higher rates of stroke and cardiovascular mortality compared to non-Hispanic whites. Methods— For the analysis, participants in the Jackson cohort of the Atherosclerosis Risk in Communities Study were followed from the date of the echocardiogram in cycle three to the date of the first ischemic stroke event (or death) or to December 31, 2004 if no ischemic stroke event (or death) was detected. Results— There were 1886 participants in the study population (mean age 58.9 years, 65% women). Participants in the top quintile of LA diameter indexed to height (LA diameter/height; 2.57 to 3.55 cm/m) were more likely women, hypertensive, diabetic, and obese compared to those not in the top quintile. Over a median follow-up of 9.8 years for ischemic stroke and 9.9 years for all-cause mortality, there were 106 strokes and 242 deaths. In a multivariable model adjusting for traditional clinical risk factors, the top quintile of LA diameter/height was significantly related to ischemic stroke (HR 1.7; 95% CI: 1.1, 2.7) and all-cause mortality (HR 2.0; 95% CI: 1.5, 2.7). After further adjustment for left ventricular (LV) hypertrophy and low LV ejection fraction, the top quintile remained significantly related to all-cause mortality (HR 1.8; 95% CI: 1.3, 2.5). Conclusions— In this population-based cohort of African Americans, LA size was a predictor of all-cause mortality after adjusting for traditional cardiovascular risk factors, LV hypertrophy, and low LV ejection fraction.

Relation of Obesity to Circulating B-Type Natriuretic Peptide Concentrations in Blacks The Jackson Heart Study

Background— Lower plasma B-type natriuretic peptide (BNP) concentrations in obese individuals (“natriuretic handicap”) may play a role in the pathogenesis of obesity-related hypertension. Whether this phenomenon may contribute to hypertension in blacks is unknown. We tested the hypothesis that body mass index is inversely related to BNP concentrations in blacks. Methods and Results— We examined the relation of plasma BNP to body mass index in 3742 Jackson Heart Study participants (mean age, 55±13; 62% women) without heart failure using multivariable linear and logistic regression, adjusting for clinical and echocardiographic covariates. The multivariable-adjusted mean BNP was higher for lean participants compared with obese participants in both normotensive (P<0.0001) and hypertensive (P<0.0012) groups. In sex-specific analyses, the adjusted mean BNP was higher in lean hypertensive individuals compared with obese hypertensive individuals for both men (20.5 versus 10.9 pg/mL, respectively; P=0.0009) and women (20.0 versus 13.8 pg/mL; P=0.011). The differences between lean and obese participants were more pronounced in normotensive participants (men, 9.0 versus 4.4 pg/mL; P<0.0001; women, 12.8 versus 8.4 pg/mL; P=0.0005). For both hypertensive and normotensive individuals in the pooled sample, multivariable-adjusted BNP was significantly related to both continuous body mass index (P<0.05 and P<0.0001, respectively) and categorical body mass index (P for trend <0.006 and <0.0001, respectively). Conclusion— Our cross-sectional study of a large community-based sample of blacks demonstrates that higher body mass index is associated with lower circulating BNP concentrations, thereby extending the concept of a natriuretic handicap in obese individuals observed in non-Hispanic whites to this high-risk population.

The Relation of Diabetes, Impaired Fasting Blood Glucose, and Insulin Resistance to Left Ventricular Structure and Function in African Americans: The Jackson Heart Study

OBJECTIVE We assessed the relation of diabetes and insulin resistance (IR) on left ventricular (LV) structure and function in African Americans. RESEARCH DESIGN AND METHODS Among those receiving echocardiograms in cycle 1 of the Jackson Heart Study, we assessed the sex-specific relation of fasting blood glucose (FBG), diabetes, and IR to LV structure and function, adjusting for age, systolic blood pressure, antihypertensive medications, and BMI. RESULTS Among 2,399 participants, LV mass index (Pwomen = 0.0002 and Pmen = 0.02), posterior wall thickness (Pwomen = 0.01 and Pmen = 0.05), and interventricular septal wall thickness (Pwomen = 0.01) were related to FBG categories. Among those with normal FBG and no diabetes, concentric remodeling and low ejection fraction in women and LV mass index and posterior wall thickness in men were related to IR. CONCLUSIONS In the largest study of its kind in a community-based cohort of African Americans, we found a relation of FBG category and IR to LV structure and function.

Association of Plasma B-Type Natriuretic Peptide Concentrations With Longitudinal Blood Pressure Tracking in African Americans Findings From the Jackson Heart Study

Water and sodium retention precedes the development of high blood pressure (BP) and explains a compensatory rise in B-type natriuretic peptide (BNP) concentrations. It is unclear whether BNP concentrations antedate the BP progression. We hypothesized that higher BNP concentrations in our African American cohort will be associated with longitudinal increases in BP, progression of BP stage, and incident hypertension. Our study sample consisted of 888 normotensive (based on BP at examination 1 [2000–2004]) participants of the Jackson Heart Study (mean age, 47±12 years; 61% women). We examined the relation of BNP concentrations at the baseline examination to change in systolic and diastolic BPs, BP progression (an increase by 1 BP stage as defined by THE sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and incident hypertension by examination 2 (2005–2008) adjusting for baseline BP stages, systolic and diastolic BPS, traditional risk factors, and echocardiographic left ventricular mass. Over a median follow-up period of 5.0±0.8 years, 36.9% progressed to a higher BP stage and 19.3% developed hypertension. In multivariable regression models, higher log-BNP concentrations at examination 1 were significantly and positively associated with changes in systolic and diastolic BPs (P<0.05 for both). Baseline log-BNP was significantly associated with BP progression (P=0.046). Every SD increase in baseline log BNP was associated with a 12% increased risk of BP progression. Log-BNP was not significantly associated with incident hypertension (P=0.12). In our community-based sample of African Americans, higher BNP concentrations predicted a longitudinal increase in systolic and diastolic BPs and progression of BP stage.

Unusual presentation of chronic myelogenous leukemia as multiple skin chloromas: report of a case with clinical and cytologic correlation.

BACKGROUND Chronic myelogenous leukemia (CML) presenting as multiple skin chloromas is an extremely rare manifestation. Though often seen in acute myelogenous leukemia, to date there have been no reported cases of CML presenting as multiple skin chloromas in the chronic phase. Chloromas in blastic phase of CML at different body sites have been reported previously. CASE A 53-year-old African American male presented to his primary care provider with multiple skin nodules. A complete blood cound showed a high white cell count, for which he was transferred to a university tertiary care center. Fine needle aspiration (FNA) of the skin lesion revealed cellular smears consisting of immature myeloid cells of CML. Based on these findings, and with clinical correlation, a preliminary diagnosis of chloroma was made and confirmed by ancillary studies. CONCLUSION This rare manifestation should alert a clinician to include CML in chronic phase in the differential diagnosis of patients presenting with multiple nonpigmented, nonpruritic skin nodules. FNA with ancillary studies can provide a rapid diagnosis.

C-reactive protein and subclinical cardiovascular disease among African-Americans: (the Jackson Heart Study).

Objective Systemic inflammation has been implicated as an early marker for subclinical cardiovascular disease; however, findings have been inconsistent in the African−American population. Methods We examined the relation of C-reactive protein (CRP) to subclinical disease in African−American participants of the Jackson Heart Study first examination. Subclinical disease evaluated included aortic valve calcification (AVC), carotid intima-medial thickness (IMT) and peripheral arterial disease (PAD). We assessed the relation of CRP to subclinical disease, adjusting for age, BMI, sex, SBP and DBP, diabetes, total/high-density lipoprotein cholesterol, triglycerides, smoking, antihypertensive therapy, lipid-lowering therapy and hormone replacement therapy. Results In the study population approximately, 5.1% of participants had AVC and 6.7% had PAD. In the age-adjusted and sex-adjusted model, CRP was significantly related to AVC (P = 0.02) and carotid IMT (P = 0.02). However, in the multivariable-adjusted logistic regression analysis, CRP was significantly related to AVC (P = 0.02) and to PAD (P = 0.04) but not to carotid IMT (P = 0.18). Conclusion We describe significant associations between CRP and AVC and PAD in a population-based cohort of African−Americans.

Relation of Obesity to Circulating B-Type Natriuretic Peptide Concentrations in Blacks

Background— Lower plasma B-type natriuretic peptide (BNP) concentrations in obese individuals (“natriuretic handicap”) may play a role in the pathogenesis of obesity-related hypertension. Whether this phenomenon may contribute to hypertension in blacks is unknown. We tested the hypothesis that body mass index is inversely related to BNP concentrations in blacks. Methods and Results— We examined the relation of plasma BNP to body mass index in 3742 Jackson Heart Study participants (mean age, 55±13; 62% women) without heart failure using multivariable linear and logistic regression, adjusting for clinical and echocardiographic covariates. The multivariable-adjusted mean BNP was higher for lean participants compared with obese participants in both normotensive (P<0.0001) and hypertensive (P<0.0012) groups. In sex-specific analyses, the adjusted mean BNP was higher in lean hypertensive individuals compared with obese hypertensive individuals for both men (20.5 versus 10.9 pg/mL, respectively; P=0.0009) and women (20.0 versus 13.8 pg/mL; P=0.011). The differences between lean and obese participants were more pronounced in normotensive participants (men, 9.0 versus 4.4 pg/mL; P<0.0001; women, 12.8 versus 8.4 pg/mL; P=0.0005). For both hypertensive and normotensive individuals in the pooled sample, multivariable-adjusted BNP was significantly related to both continuous body mass index (P<0.05 and P<0.0001, respectively) and categorical body mass index (P for trend <0.006 and <0.0001, respectively). Conclusion— Our cross-sectional study of a large community-based sample of blacks demonstrates that higher body mass index is associated with lower circulating BNP concentrations, thereby extending the concept of a natriuretic handicap in obese individuals observed in non-Hispanic whites to this high-risk population.

Association of Plasma B-Type Natriuretic Peptide Concentrations With Longitudinal Blood Pressure Tracking in African Americans

Water and sodium retention precedes the development of high blood pressure (BP) and explains a compensatory rise in B-type natriuretic peptide (BNP) concentrations. It is unclear whether BNP concentrations antedate the BP progression. We hypothesized that higher BNP concentrations in our African American cohort will be associated with longitudinal increases in BP, progression of BP stage, and incident hypertension. Our study sample consisted of 888 normotensive (based on BP at examination 1 [2000–2004]) participants of the Jackson Heart Study (mean age, 47±12 years; 61% women). We examined the relation of BNP concentrations at the baseline examination to change in systolic and diastolic BPs, BP progression (an increase by 1 BP stage as defined by THE sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and incident hypertension by examination 2 (2005–2008) adjusting for baseline BP stages, systolic and diastolic BPS, traditional risk factors, and echocardiographic left ventricular mass. Over a median follow-up period of 5.0±0.8 years, 36.9% progressed to a higher BP stage and 19.3% developed hypertension. In multivariable regression models, higher log-BNP concentrations at examination 1 were significantly and positively associated with changes in systolic and diastolic BPs (P<0.05 for both). Baseline log-BNP was significantly associated with BP progression (P=0.046). Every SD increase in baseline log BNP was associated with a 12% increased risk of BP progression. Log-BNP was not significantly associated with incident hypertension (P=0.12). In our community-based sample of African Americans, higher BNP concentrations predicted a longitudinal increase in systolic and diastolic BPs and progression of BP stage.

Association of Plasma B-Type Natriuretic Peptide Concentrations With Longitudinal Blood Pressure Tracking in African AmericansNovelty and Significance

Water and sodium retention precedes the development of high blood pressure (BP) and explains a compensatory rise in B-type natriuretic peptide (BNP) concentrations. It is unclear whether BNP concentrations antedate the BP progression. We hypothesized that higher BNP concentrations in our African American cohort will be associated with longitudinal increases in BP, progression of BP stage, and incident hypertension. Our study sample consisted of 888 normotensive (based on BP at examination 1 [2000–2004]) participants of the Jackson Heart Study (mean age, 47±12 years; 61% women). We examined the relation of BNP concentrations at the baseline examination to change in systolic and diastolic BPs, BP progression (an increase by 1 BP stage as defined by THE sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and incident hypertension by examination 2 (2005–2008) adjusting for baseline BP stages, systolic and diastolic BPS, traditional risk factors, and echocardiographic left ventricular mass. Over a median follow-up period of 5.0±0.8 years, 36.9% progressed to a higher BP stage and 19.3% developed hypertension. In multivariable regression models, higher log-BNP concentrations at examination 1 were significantly and positively associated with changes in systolic and diastolic BPs (P<0.05 for both). Baseline log-BNP was significantly associated with BP progression (P=0.046). Every SD increase in baseline log BNP was associated with a 12% increased risk of BP progression. Log-BNP was not significantly associated with incident hypertension (P=0.12). In our community-based sample of African Americans, higher BNP concentrations predicted a longitudinal increase in systolic and diastolic BPs and progression of BP stage.