Jacqueline D. Wright

Serum Total Homocysteine Concentrations in the Third National Health and Nutrition Examination Survey (1991-1994): Population Reference Ranges and Contribution of Vitamin Status to High Serum Concentrations

Homocysteine, a non-protein-forming sulfur amino acid, has attracted attention because elevated concentrations of circulating total homocysteine are associated with an increased risk for vascular disease (1, 2). Homocysteine is also a sensitive functional marker of inadequate cellular folate and vitamin B12 concentrations (3). Inadequate status of these vitamins has important health consequences that may be independent of their role in homocysteine metabolism. Low folate concentrations increase a womans risk for having a baby with a neural tube defect (4, 5), and an inadequate vitamin B12 concentration is known to produce various neurologic and cognitive effects (6, 7). Persons with low circulating folate or vitamin B12 concentrations have higher fasting total homocysteine concentrations (8-10), and elevated fasting total homocysteine concentrations are usually normalized by treatment with folic acid and vitamin B12 (6, 11-14). However, less is known about the importance of these vitamins as risk factors for high homocysteine concentration in the general population. Only three studies have examined the relation between homocysteine concentration and its vitamin determinants in samples that were designed to be representative of U.S. national (8) or regional (9, 10) populations. One of these studies (9) reported that approximately two thirds of all cases of moderately elevated total homocysteine concentrations were potentially attributable to low vitamin concentrations, but estimation of the proportion of cases with high homocysteine concentrations that can be attributed to inadequate vitamin status is complicated by the lack of a standard definition of a high total homocysteine concentration. In the absence of a definition based on increased risk for an adverse health outcome, such as vascular disease, upper reference limits from samples of healthy persons without established risk factors for high homocysteine concentrations have been used to define a high total homocysteine concentration (10, 15-17). We previously described the distribution of total serum homocysteine concentrations in participants 12 years of age or older from the third National Health and Nutrition Examination Survey (NHANES III), a population-based sample of U.S. residents (18). These data present a unique opportunity to develop population reference ranges for serum total homocysteine concentration and to determine the extent to which elevated homocysteine concentrations are associated with low circulating vitamin concentrations in a representative sample of U.S. residents. Methods Participants The NHANES III was developed to obtain nationally representative information on the health and nutritional status of the civilian, noninstitutionalized U.S. population (19, 20). Homocysteine concentrations were measured as part of an NHANES III surplus sera project on serum samples from participants 12 years of age or older who were seen during phase II of this survey (19911994). This project is described in greater detail elsewhere (18). Homocysteine concentrations were measured at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University by using the high-performance liquid chromatography method of Araki and Sako (21). The interassay coefficient of variation for this assay was 6%. Folate and vitamin B12 were determined for phase 2 specimens at the Centers for Disease Control and Prevention central laboratory by using a Quanta Phase II radioassay kit (Bio-Rad Laboratories, Hercules, California), and analyses are described in detail in the NHANES III Laboratory Procedures Manual (22). The coefficients of variation for folate and vitamin B12 were 6% and 7%, respectively. Informed consent was obtained from all respondents. The NHANES III protocol was approved by the National Center for Health Statistics NHANES Institutional Review Board, and measurement of serum homocysteine was approved by the Human Investigations Review Committee at the New England Medical Center. We used the following search strategy, combining Medical Subject Headings (MeSH terms) and text words, to identify all population-based studies relating vitamin status to circulating homocysteine concentrations: ([homocysteine (MeSH] OR homocysteine [Text Word]) AND (vitamins [MeSH] OR vitamin [Text Word]]) AND (epidemiologic studies [MeSH] OR data collection [MeSH] OR survey [Text Word]]. This search identified 137 citations, of which 16 were reviews. We selected original studies that 1) were designed to be representative of national, regional, or local populations and 2) described the relation between circulating homocysteine concentrations and either intake or circulating concentrations of folate or vitamin B12. As of 1 March 1999, 3 articles met our criteria (8-10). Statistical Analysis We used sample weights in analyses to account for unequal probability of selection and nonresponse and to produce estimates of means and percentiles that were representative of the noninstitutionalized, civilian U.S. population. We used SUDAAN statistical software (23) to account for the complex survey design in the variance estimates. Because total homocysteine, folate, and vitamin B12 values were skewed, logarithmic transformations were applied. To show the relations between total homocysteine concentrations and vitamin concentrations, we classified participants into age- and sex-specific vitamin decile categories and estimated the geometric mean of the serum total homocysteine concentration within each decile. Analyses were adjusted for ethnicity and serum creatinine concentration. In addition, the relation between total homocysteine and folate concentrations was adjusted for vitamin B12 concentrations, and the relation between total homocysteine and vitamin B12 was adjusted for folate concentrations. We tested the associations between homocysteine and vitamins for interactions with age, sex, and ethnicity. We tested for trend of total homocysteine concentration across vitamin concentrations by using linear regression with the logarithm of the continuous vitamin concentration as the independent variable, adjusting as described above. We showed the trend by using the SYSTAT LOWESS procedure to fit smoothed curves (24) to the geometric mean total homocysteine concentrations in the vitamin decile categories (25). It has been suggested that population reference ranges for the total homocysteine concentration be established in samples of persons without established risk factors for a high homocysteine concentration (10, 15-17). For our reference sample, we included persons whom we assumed to be folate- and vitamin B12-replete (that is, their serum concentrations of both vitamins were above the 50th percentile) and had normal serum creatinine concentrations (<90 mol/L for women and<110 mol/L for men). Pregnant women were excluded. We used the 5th and the 95th percentiles from the reference sample to estimate population reference ranges. To identify the potential impact of low vitamin concentrations on high total homocysteine concentration, we needed to establish values for high total homocysteine and low vitamin concentrations. We used the sex-specific 95th percentiles in the participants 20 to 39 years of age (the reference sample) to define high total homocysteine concentrations for all age groups. We used this reference sample because homocysteine concentrations changed little with age in this group, unlike in the other age groups (18). We defined low vitamin concentrations as a folate concentration less than 11 nmol/L (26, 27) and a vitamin B12 concentration less than 185 pmol/L (28, 29). We calculated the prevalence of high total homocysteine concentration; the prevalence ratio for high total homocysteine concentration; the attributable risk percentage; and the population attributable risk percentage for persons with low concentrations of folate, vitamin B12, or both compared with persons who had adequate concentrations of both of these vitamins. The attributable risk percentage estimates the excess cases of high homocysteine concentrations among persons with low vitamin concentrations, whereas the population attributable risk percentage takes into account the prevalence of low vitamin concentrations in the population and estimates the excess of high homocysteine concentrations associated with low vitamin concentrations in the entire population. We used the design effect for total homocysteine concentration, which is the ratio of the complex sampling design variance derived by using SUDAAN software (23) to the simple random sample variance calculated by using SAS software (30), to determine the recommended minimum sample size needed to achieve stable estimates of means, proportions, and percentiles according to the National Center for Health Statistics analytic guidelines (19). On the basis of an average design effect of approximately 1.4 for our sample, means and medians derived from fewer than 42 participants, 10th and 90th percentiles derived from fewer than 112 participants, and 5th and 95th percentiles derived from fewer than 224 participants were deemed unstable. Sample size for stable estimates of the proportions varied by the magnitude of the proportion, ranging from 42 for proportions of 0.5 to 224 for proportions of 0.05 or 0.95. We indicate in the text and tables statistics that did not meet the appropriate sample size. We categorized participants into three ethnic groups: non-Hispanic white, non-Hispanic black, and Mexican American. We excluded persons from other ethnic groups (n=436) because their inclusion produced unstable estimates of mean total homocysteine concentration after adjustment for ethnicity. Our analyses are based on 8086 participants with complete data on serum total homocysteine, folate, vitamin B12, and creatinine concentrations. Results Table 1 shows selected characteristics of the sample by sex and ethnic group. On average, non-Hispanic white pa

Zinc Intake of the U.S. Population: Findings from the Third National Health and Nutrition Examination Survey, 1988–1994

National survey data for 29,103 examinees in the third National Health and Nutrition Examination Survey were used to estimate mean and percentile distributions of dietary and total zinc intakes based on 24-h dietary recalls and vitamin/supplement use. Mean daily total intakes ranged from 5.5 mg in non-breast-feeding infants to 13 mg in adults and were higher in adolescent and adult males than in females (P <0.01). Mean total zinc intakes (22 mg) were approximately 10 mg higher in pregnant and lactating females than in nonpregnant, nonlactating females of the same age. Mean total zinc intakes were 0. 7 mg higher in adolescents (11.1 mg) and 2.5-3.5 mg higher in adults (13 mg) compared with mean dietary intakes, indicating the average contribution of supplements to total zinc intake. Mean total zinc intakes were significantly higher in non-Hispanic whites than in non-Hispanic blacks (P<0.01) and Mexican Americans (P<0.01) for men and women aged 51-70 y and > or =71 y due to higher zinc supplement use. The prevalence of zinc-containing supplements use ranged from 0. 1% in infants to 20.5% in adults. Adequate zinc intake in this survey population was 55.6% based on total intakes of >77% of the 1989 recommended dietary allowance. Young children aged 1-3 y, adolescent females aged 12-19 y and persons aged > or =71 y were at the greatest risk of inadequate zinc intakes.

Awareness of Federal Dietary Guidance in Persons Aged 16 Years and Older: Results from the National Health and Nutrition Examination Survey 2005-2006

The National Health and Nutrition Examination Survey 2005-2006 included questions on awareness of the Dietary Guidelines for Americans (DGA), the Food Guide Pyramid, and the 5 A Day for Better Health Program. Prevalence of awareness of federal dietary guidance was estimated and differences were tested across demographic traits, health characteristics, and diet-related attitudes and behavior. The continuous National Health and Nutrition Examination Survey uses a nationally representative cross-sectional sample design. The analytic sample consisted of 5,499 persons aged 16 years and older with complete data. Among persons aged 16 years and older, 83.8% had heard of at least one of the initiatives: 49.2% had heard of the DGA, 80.6% had heard of the Food Guide Pyramid, and 51.2% had heard of the 5 A Day program. There was a linear trend of decreasing awareness of at least one of the guidance efforts with increasing age. Differences by sex, race/ethnicity, education, and income were also observed. Differences by body mass index were not statistically significant; however, significant differences were seen with fatalistic beliefs about body weight. Differences by smoking, self-assessed diet quality, and eating out frequency were not statistically significant after adjustment for sex, age, race/ethnicity, education, and income. These results may be useful in promotion of the upcoming edition of the DGA and to suggest population groups that may benefit from strengthened and more innovative education efforts at the public health program level and at the clinic level.

Feasibility of collecting 24-h urine to monitor sodium intake in the National Health and Nutrition Examination Survey

BACKGROUNDnTwenty-four-hour urine sodium excretion is recommended for monitoring population sodium intake. Because of concerns about participation and completion, sodium excretion has not been collected previously in US nationally representative surveys.nnnOBJECTIVEnWe assessed the feasibility of implementing 24-h urine collections as part of a nationally representative survey.nnnDESIGNnWe selected a random half sample of nonpregnant US adults aged 20-69 y in 3 geographic locations of the 2013 NHANES. Participants received explicit instructions, started and ended the urine collection in a urine study mobile examination center, and answered questions about their collection. Among those with a complete 24-h urine collection, a random one-half were asked to collect a second 24-h urine sample. Sodium, potassium, chloride, and creatinine excretion were analyzed.nnnRESULTSnThe final NHANES examination response rate for adults aged 20-69 y in these 3 study locations was 71%. Of those examined (n = 476), 282 (59%) were randomly selected to participate in the 24-h urine collection. Of these, 212 persons [75% of those selected for 24-h urine collection; 53% (equal to 71% × 75% of those selected for the NHANES)] collected a complete initial 24-h specimen and 92 persons (85% of 108 selected) collected a second complete 24-h urine sample. More men than women completed an initial collection (P = 0.04); otherwise, completion did not vary by sociodemographic characteristics, body mass index, education, or employment status for either collection. Mean 24-h urine volume and sodium excretion were 1964 ± 1228 mL and 3657 ± 2003 mg, respectively, for the first 24-h urine sample, and 2048 ± 1288 mL and 3773 ± 1891 mg, respectively, for the second collection.nnnCONCLUSIONnGiven the 53% final component response rate and 75% completion rate, 24-h urine collections were deemed feasible and implemented in the NHANES 2014 on a subsample of adults aged 20-69 y to assess population sodium intake. This study was registered at clinicaltrials.gov as NCT02723682.

The Impact of Differences in Methodology and Population Characteristics on the Prevalence of Hypertension in US Adults in 1976–1980 and 1999–2002

BACKGROUNDnResults from the National Health and Nutrition Examination Survey (NHANES) indicate that hypertension prevalence declined by 9% points from 34% in 1976-1980 to 25% in 1999-2002 in adults 20-74 years. The purpose of this study was to estimate the impact on hypertension prevalence of measurement error and selected risk factors.nnnMETHODSnUsing cross-sectional survey data from NHANES, we estimated the effect on hypertension of incorrect blood pressure (BP) cuff size and zero end-digit preference and the effect of changes in the distribution of age, body mass index (BMI), sex, race-ethnicity, smoking, and education. The analytic sample of persons 20-74 years consisted of 11,563 from 1976-1980 and 7,901 from 1999-2002 NHANES. Covariate-adjusted prevalences were calculated using log-linear regression models to produce predictive margins.nnnRESULTSnAfter adjustment to age, BMI, sex, race-ethnicity, smoking, and education, the prevalence difference became higher, changing from -9% (95% confidence interval (CI): -11, -6) to -14% (95 CI: -17, -11). After adjustment to these risk factors and correction for measurement error the prevalence difference was -9% (95 CI: -11, -6).nnnCONCLUSIONSnMeasurement error, mainly from cuff size differences, inflated the temporal decline in hypertension prevalence. The results indicate that age, sex, race-ethnicity, smoking, or education did not fully explain the lower prevalence of measured hypertension in all BMI groups and suggest that a change in some unmeasured factor or factors contributed to the decline.

Heart Failure Stages Among Older Adults in the CommunityClinical Perspective: The Atherosclerosis Risk in Communities Study

Background: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear.nnMethods: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67–91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization).nnResults: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index ( P =0.028) and integrated discrimination index ( P =0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e’, E/e’, and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants.nnConclusions: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.nn# Clinical Perspective {#article-title-62}Background: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear. Methods: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67–91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization). Results: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index (P=0.028) and integrated discrimination index (P=0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e’, E/e’, and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. Conclusions: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.

Heart Failure Stages Among Older Adults in the CommunityClinical Perspective

Background: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear.nnMethods: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67–91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization).nnResults: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index ( P =0.028) and integrated discrimination index ( P =0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e’, E/e’, and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants.nnConclusions: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.nn# Clinical Perspective {#article-title-62}Background: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear. Methods: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67–91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization). Results: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index (P=0.028) and integrated discrimination index (P=0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e’, E/e’, and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. Conclusions: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.

Contemporary Assessment of Left Ventricular Diastolic Function in Older AdultsClinical Perspective: The Atherosclerosis Risk in Communities Study

Background: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk. Methods: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67–90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e’, E/e’, and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. Results: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e’ (4.6 and 5.2 cm/s for septal and lateral TDI e’, respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e’ and left atrial size demonstrated good agreement with guideline cut points. TDI e’ was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y). Conclusions: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.Background: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk.nnMethods: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67–90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e’, E/e’, and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors.nnResults: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e’ (4.6 and 5.2 cm/s for septal and lateral TDI e’, respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e’ and left atrial size demonstrated good agreement with guideline cut points. TDI e’ was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement ( P <0.001) and continuous net reclassification improvement ( P <0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y).nnConclusions: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.nn# Clinical Perspective {#article-title-44}

Contemporary Assessment of Left Ventricular Diastolic Function in Older AdultsClinical Perspective

Background: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk. Methods: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67–90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e’, E/e’, and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. Results: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e’ (4.6 and 5.2 cm/s for septal and lateral TDI e’, respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e’ and left atrial size demonstrated good agreement with guideline cut points. TDI e’ was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y). Conclusions: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.Background: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk.nnMethods: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67–90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e’, E/e’, and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors.nnResults: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e’ (4.6 and 5.2 cm/s for septal and lateral TDI e’, respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e’ and left atrial size demonstrated good agreement with guideline cut points. TDI e’ was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement ( P <0.001) and continuous net reclassification improvement ( P <0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y).nnConclusions: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.nn# Clinical Perspective {#article-title-44}