Prevalence of Elevated NT-proBNP and its Prognostic Value by Blood Pressure Treatment and Control- National Health and Nutrition Examination Survey, 1999-2004.

Background: The prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population. Methods: We measured NT-proBNP among adults aged 20 years who participated in the 1999-2004 National Health and Nutrition Examination Survey. In adults without a history of cardiovascular disease, we assessed the prevalence of elevated NT-pro-BNP by blood pressure (BP) treatment and control categories. We examined the extent to which NT-proBNP identifies participants at higher risk for mortality across BP treatment and control categories. Results: The number of US adults without CVD with elevated NT-proBNP (≥125 pg/ml) was 6.2 million among those with untreated hypertension, 4.6 million among those with treated controlled hypertension, and 5.4 million among those with treated uncontrolled hypertension. After adjusting for age, sex, body mass index, and race/ethnicity, participants with treated controlled hypertension and elevated NT-proBNP had increased risk of all-cause mortality (HR 2.29, 95% CI 1.79, 2.95) and increased risk of cardiovascular mortality (HR 3.83, 95% CI: 2.34, 6.29), compared to those without hypertension and with low levels of NT-proBNP (<125 pg/ml). Among those on antihypertensive medication, those with SBP 130-139 mm Hg and elevated NT-proBNP had increased risk of all-cause mortality, compared to those with SBP<120 mm Hg and low levels of NT-proBNP. Conclusions: Among a general population of adults free of cardiovascular disease, NT-proBNP can provide additional prognostic information within and across categories of BP. Measurement of NT-proBNP may have potential for clinical use to optimize hypertension treatment.

Serum magnesium, bone-mineral metabolism markers and their interactions with kidney function on subsequent risk of peripheral artery disease: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium-PAD relationship is independent of or modified by kidney function. METHODS: A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990-92) was studied. We investigated the association of serum magnesium and other bone-mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression. RESULTS: Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40-2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n = 233) with P-for-interaction 0.03. Among bone-mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2. CONCLUSIONS: Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population.

Hypertension Awareness, Treatment, and Control in US Adults: Trends in the Hypertension Control Cascade by Population Subgroup (National Health and Nutrition Examination Survey, 1999-2016).

Examination of changes in hypertension awareness, treatment, and control (i.e., the hypertension control cascade) by population subgroup can inform targeted efforts to improve hypertension control and reduce disparities. We analyzed 1999-2016 data from the National Health and Nutrition Examination Survey and examined trends across 6-year periods in hypertension awareness, treatment, and control by age, sex, and race/ethnicity. We included 39,589 participants (16,141 with hypertension). Hypertension awareness, treatment, and control increased from 1999 to 2016 among all age groups. However, there were few changes after 2010. Across all time periods, awareness, treatment, and control were higher among younger women (ages 25-44 years) than among younger men, while control was higher among older men (ages ≥65 years) than among older women. Hypertension control was persistently lower for blacks than for whites of all ages, and awareness, treatment, and control were lower among younger Hispanics. There have been few changes in hypertension awareness, treatment, and control since 2010. Disparities in hypertension control by sex highlight the need for effective interventions among younger men and older women. Concerted efforts are also needed to reduce persistent racial/ethnic disparities, particularly to improve treatment control among blacks and to further address gaps at all stages among younger Hispanics.

Dietary phosphorus intake and blood pressure in adults: a systematic review of randomized trials and prospective observational studies.

BACKGROUND: Elevated blood pressure (BP) is a major cause of preventable disease in the United States and around the world. It has been postulated that phosphorus intake may affect BP, with some studies suggesting a direct and others an inverse association. OBJECTIVES: We systematically reviewed the literature on the association of dietary phosphorus with BP in adults and performed a qualitative synthesis. METHODS: We included randomized and nonrandomized behavioral intervention and feeding studies (intervention studies) and prospective observational studies that measured dietary phosphorus intake or urinary phosphorus excretion and BP. We excluded studies of supplements, children, or individuals with major medical conditions. We searched PubMed, Embase, Cochrane Trials, and clinicaltrials.gov on 1 June, 2017 and 22 August, 2018. We assessed studies' risk of bias in their assessment of phosphorus exposure and BP. RESULTS: We reviewed 4759 publications and included 14 intervention studies (2497 participants), 3 prospective observational cohorts (17,795 participants), and 2 ongoing trials. No included intervention studies were designed specifically to achieve a phosphorus contrast. Two studies found a significant positive association of dietary phosphorus with systolic BP, 4 a significant inverse association, and 8 no significant association. Four studies found a significant inverse association with diastolic BP and 10 no significant associations. Two cohorts found lower risk of incident hypertension comparing the highest with the lowest quintiles of phosphorus intake and 1 found no significant difference: HR: 0.86 (95% CI: 0.75, 0.98); HR: 0.83 (95% CI: 0.68, 1.02); and HR: 0.75 (95% CI: 0.45, 1.27), respectively. CONCLUSIONS: We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association. This trial was registered at www.crd.york.ac.uk/prospero/ as CRD42017062489.

The Percentage of Dietary Phosphorus Excreted in the Urine Varies by Dietary Pattern in a Randomized Feeding Study in Adults.

BACKGROUND: Urinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors. OBJECTIVE: We assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial. METHODS: DASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test. RESULTS: At the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P = 0.74 control vs. FV, P < 0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). CONCLUSIONS: These findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054.

Coffee consumption and liver-related hospitalizations and deaths in the ARIC study.

BACKGROUND/OBJECTIVES: Coffee consumption has been found to be associated with reduced risk of chronic conditions such as liver disease. However, less is known about the association between coffee and liver-related hospitalizations and deaths. SUBJECTS/METHODS: We conducted a prospective analysis on 14,208 participants aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study. Coffee consumption (cups/day) was assessed using food frequency questionnaires at visit 1 (1987-89) and visit 3 (1993-95). Liver-related hospitalizations were defined as a hospitalization with any International Classification of Diseases, Ninth Revision (ICD-9) code related to liver disease identified through cohort surveillance. Liver-related death was defined as any death with a liver disease ICD-9 code listed anywhere on the death certificate form. RESULTS: There were 833 incident cases of liver-related hospitalizations over a median follow-up of 24 years and 152 liver-related deaths over a median follow-up of 25 years. Participants who were in the highest category of coffee consumption (≥ 3 cups/day) were more likely to be men, whites, current smokers, and current alcohol drinkers. In our fully adjusted model, consuming ≥ 3 cups/day of coffee was significantly associated with a reduced risk of liver-related hospitalizations compared with never drinkers (hazard ratio: 0.79, 95% CI: 0.63-0.99). There were no significant associations between coffee consumption and liver-related deaths after adjusting for covariates. CONCLUSIONS: Coffee drinkers may be at lower risk for liver-related hospitalizations. This supports current evidence that low and moderate levels of coffee may be protective to the liver.

Coffee Consumption and Incident Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Moderate coffee consumption has been suggested to be associated with lower risk for chronic conditions such as diabetes, a major precursor to chronic kidney disease (CKD). However, the association between coffee and CKD has not been fully established. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 14,209 participants aged 45 to 64 years from the Atherosclerosis Risk in Communities (ARIC) Study. PREDICTORS: Coffee consumption (cups per day) was assessed at visits 1 (1987-1989) and 3 (1993-1995) using food frequency questionnaires. OUTCOMES: Incident CKD defined as estimated glomerular filtration rate < 60mL/min/1.73m2 accompanied by ≥25% estimated glomerular filtration rate decline, CKD-related hospitalization or death, or end-stage renal disease. RESULTS: There were 3,845 cases of incident CKD over a median of 24 years of follow-up. Men, whites, current smokers, and participants without comorbid conditions were more likely to consume higher amounts of coffee per day. After adjustment for demographic, clinical, and dietary factors, higher categories of coffee consumption were associated with lower risk for incident CKD compared with those who never consumed coffee (HR for <1 cup per day, 0.90 [95% CI, 0.82-0.99]; 1-<2 cups per day, 0.90 [95% CI, 0.82-0.99]; 2-<3 cups per day, 0.87 [95% CI, 0.77-0.97]; and ≥3 cups per day, 0.84 [95% CI, 0.75-0.94]). In continuous analysis, for each additional cup of coffee consumed per day, risk for incident CKD was lower by 3% (HR, 0.97; 95% CI, 0.95-0.99; P<0.001). LIMITATIONS: Self-reported coffee consumption and observational design. CONCLUSIONS: Participants who drank higher amounts of coffee had lower risk for incident CKD after adjusting for covariates. Coffee consumers may not be at adverse risk for kidney disease.

Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

BACKGROUND AND AIMS: Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. METHODS: Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS: During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS: Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.

Serum fibroblast growth factor-23 and incident hypertension: the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Elevated serum fibroblast growth factor-23 (FGF23), an endogenous hormone, is associated with disturbed mineral homeostasis, cardiovascular disease, and chronic kidney disease. It is unclear whether FGF23 impacts the development of incident hypertension. We examined the association between elevated FGF23 and incident hypertension in a community-based cohort. METHOD: We investigated the association of serum FGF23, measured at baseline (1990-1992), with incident hypertension at two follow-up visits (1993-1995 and 1996-1998) in 7948 middle-aged men and women without hypertension at baseline participating in the Atherosclerosis Risk in Communities Study. Incident hypertension was determined by measured blood pressure (DBP ≥ 90 mmHg or SBP ≥ 140 mmHg) and/or self-reported hypertension medication use at follow-up exams. Complementary log-log models that accounted for interval censoring were used to model the association between FGF23 and incident hypertension. RESULTS: During a median follow-up of 5.9 years, 27% (2152/7948) participants developed hypertension. A nonlinear association between serum FGF23 and incident hypertension was observed; only persons in the highest decile of serum FGF23 had an increased risk of incident hypertension. After adjustment for demographics, behaviors, and adiposity, the hazard ratio for incident hypertension was 1.24 (95% confidence interval: 1.11, 1.39) for the highest decile of FGF23 compared with the lowest quintile. The association was further attenuated in the final model after adjusting for renal function (hazard ratio: 1.21, 95% confidence interval: 1.08, 1.35). CONCLUSION: High levels (≥60.6 pg/ml) of FGF23 are associated with a modestly increased risk of incident hypertension in the general population, independent of kidney function.

Alternative HbA1c cutoffs to identify high-risk adults for diabetes prevention: a cost-effectiveness perspective.

BACKGROUND: New recommendations about the use of hemoglobin A1c (HbA1c) for diagnosing diabetes have stimulated a debate about the optimal HbA1c cutoff to identify prediabetes for preventive intervention. PURPOSE: To assess the cost effectiveness associated with the alternative HbA1c cutoffs for identifying prediabetes. METHODS: A Markov simulation model was used to examine the cost effectiveness associated with a progressive 0.1% decrease in the HbA1c cutoff from 6.4% to 5.5%. The target population was the U.S. nondiabetic population aged ≥18 years. The simulation sample was created using the data of nondiabetic American adults from the National Health and Nutritional Examination Survey (NHANES 1999-2006). People identified as having prediabetes were assumed to receive a preventive intervention, with effectiveness the same as that in the Diabetes Prevention Program study under a high-cost intervention (HCI) scenario and in the Promoting a Lifestyle of Activity and Nutrition for Working to Alter the Risk of Diabetes study under a low-cost intervention (LCI) scenario. The analysis was conducted for a lifetime horizon from a healthcare system perspective. RESULTS: Lowering the HbA1c cutoff would increase the health benefits of the preventive interventions at higher costs. For the HCI, lowering the HbA1c cutoff from 6.0% to 5.9% and from 5.9% to 5.8% would result in $27,000 and $34,000 per QALY gained, respectively. Continuing to decrease the cutoff from 5.8% to 5.7%, from 5.7% to 5.6%, and from 5.6% to 5.5% would cost $45,000, $58,000, and $96,000 per QALY gained, respectively. For the LCI, lowering the HbA1c cutoff from 6.0% to 5.9% and from 5.9% to 5.8% would result in $24,000 and $27,000 per QALY gained, respectively. Continuing to lower the cutoff from 5.8% to 5.7%, 5.7% to 5.6%, and 5.6% to 5.5% would cost $34,000, $43,000 and $70,000 per QALY gained, respectively. CONCLUSIONS: Lowering the HbA1c cutoff for prediabetes leads to less cost-effective preventive interventions. Assuming a conventional $50,000/QALY cost-effectiveness benchmark, the HbA1c cutoffs of 5.7% and higher were found to be cost effective. Lowering the cutoff from 5.7% to 5.6% also may be cost effective, however, if the costs of preventive interventions were to be lowered.

Statin drugs, serum cholesterol, and prostate-specific antigen in the National Health and Nutrition Examination Survey 2001-2004.

PURPOSE: We evaluated the associations of statins and serum cholesterol with PSA to understand whether the inverse associations of statins and low cholesterol with aggressive prostate cancer are explained by detection bias. METHODS: We analyzed data from 2,574 men aged > or =40 years without prostate cancer in The National Health and Nutrition Examination Survey 2001-2004. We estimated multivariable-adjusted geometric mean PSA by statin use and cholesterol quintiles. To limit the influence of correlates of statin use and cholesterol on PSA, we stratified by comorbidities. RESULTS: Statin users had a non-statistically significantly lower PSA than non-users (0.90 vs. 0.95 ng/mL, p = 0.22), especially in men without comorbidities (n = 1,680; 0.86 vs. 0.99 ng/mL p = 0.02). In men with comorbidities, statin users had a non-statistically significantly higher PSA than non-users (0.91 vs. 0.83 ng/mL, p = 0.14). Men with lower cholesterol had lower PSA (bottom vs. top quintile: 0.92, 1.02 ng/mL, p-trend = 0.06). CONCLUSION: Statin users and men with lower cholesterol may have lower PSA. If so, the probability of detecting asymptomatic prostate cancer might be lower at present, but these cases might be more likely to be diagnosed at an advanced stage in the future. Thus, PSA-associated bias is unlikely to explain the inverse association of statins with advanced prostate cancer.