Brigham and Women's Hospital, Boston, Massachusetts.
Akershus University Hospital, Lørenskog, Norway.
JAMA Cardiol. 2018 Oct 1;3(10):1000-1005. doi: 10.1001/jamacardio.2018.2568.
Contemporary clinical trials of heart failure with preserved ejection fraction (HFpEF) apply natriuretic peptide (NP) thresholds to identify patients who are more likely to have the disease of interest and to enrich the baseline risk of the enrolled cohort.
To determine whether age, race/ethnicity, obesity, renal function, and atrial fibrillation (AF) affect the levels of NPs in HFpEF and whether the prognostic significance of NPs varies in these clinically important subgroups.
DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT) evaluated the distribution and prognostic significance of NPs across 6 subgroups comprising 1057 adult patients (60%) in the Americas region of TOPCAT with symptomatic heart failure (HF) and a left ventricular ejection fraction of 45% or more with available NPs at baseline.
Natriuretic peptides were log-transformed and standardized (expressed per 1 SD, z score) and assessed in 6 subgroups: age (cutoff, 70 years), black race, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared; cutoff, 30 kg/m2), waist circumference (cutoff, 102 cm for men, 88 cm for women), estimated glomerular filtration rate (cutoff, 60 mL/min/1.73 m2), and a history of AF.
Time to composite cardiovascular death, hospitalization for HF, or aborted cardiac arrest at mean (SD) 2.4-year (1.5) follow-up.
Of 1057 participants, the mean (SD) age was 72 (10) years, 183 (17.3%) were black, the mean (SD) BMI was 33.4 (8.6) kg/m2, the mean (SD) estimated glomerular filtration rate was 64.6 (21.8) mL/min/1.73 m2, and 472 (45%) had a history of AF. Median B-type NP (n = 698) and N-terminal pro-B-type NP concentrations (n = 359) were 257 (interquartile range, 149-443) ng/L and 959 (interquartile range, 554-2015) ng/L, respectively. Natriuretic peptide concentrations varied by up to 0.5 SD within the 6 subgroups, being higher in older patients with nonblack race, a lower BMI, a lower waist circumference, a lower estimated glomerular filtration rate, and a history of AF. Elevated NP levels (per 1-SD increase) were independently associated with an increased risk of the primary outcome (adjusted hazard ratio, 1.36; 95% CI, 1.22-1.54; P < .001) consistently across all investigated subgroups (interaction P > .05). In TOPCAT Americas (n = 1767), 791 (45%) were enrolled based on elevated NP levels as the qualifying criterion (as opposed to a history of HF hospitalization). This proportion was 31% (93 of 302), 34% (258 of 760), and 39% (443 of 1144) for black race, younger than 70 years, and a BMI of 30 kg/m2 or greater, respectively.
Natriuretic peptides remain important biomarkers of prognosis in HFpEF, even in subgroups who tend to have lower NP levels. A single, absolute NP threshold for inclusion in contemporary HFpEF trials may lead to an underrepresentation of certain demographic and clinical subgroups.
ClinicalTrials.gov Identifier: NCT00094302.
心力衰竭伴射血分数保留（HFpEF）的当代临床试验应用利钠肽（NP）阈值来识别更有可能患有该疾病的患者，并丰富入组队列的基线风险。
确定年龄、种族/民族、肥胖、肾功能和心房颤动（AF）是否影响 HFpEF 中 NPs 的水平，以及 NPs 的预后意义是否在这些临床重要亚组中存在差异。
设计、地点和参与者：这项对醛固酮拮抗剂治疗保留心功能心力衰竭试验（TOPCAT）的二次分析评估了 NP 在 6 个亚组中的分布和预后意义，该亚组包括 1057 名成年患者（60%），这些患者来自 TOPCAT 的美洲地区，患有有症状的心力衰竭（HF），左心室射血分数为 45%或更高，且基线时可获得 NP。
利钠肽经对数转换和标准化（表示为每 1 个标准差，z 分数），并在 6 个亚组中进行评估：年龄（截止值为 70 岁）、黑人种族、体重指数（BMI；计算为体重除以身高的平方，体重指数的截止值为 30kg/m2）、腰围（男性截止值为 102cm，女性截止值为 88cm）、估算肾小球滤过率（截止值为 60ml/min/1.73m2）和 AF 病史。
平均（标准差）2.4 年（1.5）随访期间复合心血管死亡、HF 住院或心脏骤停中止的时间。
在 1057 名参与者中，平均（标准差）年龄为 72（10）岁，183 人（17.3%）为黑人，平均（标准差）BMI 为 33.4（8.6）kg/m2，平均（标准差）估算肾小球滤过率为 64.6（21.8）ml/min/1.73m2，472 人（45%）有 AF 病史。中位 B 型 NP（n=698）和 N 端前 B 型 NP 浓度（n=359）分别为 257（四分位距，149-443）ng/L 和 959（四分位距，554-2015）ng/L。NP 浓度在 6 个亚组中相差 0.5 个标准差，年龄较大、非黑人种族、BMI 较低、腰围较小、估算肾小球滤过率较低和有 AF 病史的患者 NP 浓度较高。升高的 NP 水平（每 1 个标准差增加）与主要结局的风险增加独立相关（调整后的危险比，1.36；95%CI，1.22-1.54；P<0.001），在所有研究的亚组中一致（交互 P>0.05）。在 TOPCAT 美洲（n=1767）中，根据升高的 NP 水平作为合格标准（而不是 HF 住院史）入组了 791 人（45%）。这一比例分别为黑人种族、年龄小于 70 岁和 BMI 为 30kg/m2 或更高的 31%（93/302）、34%（258/760）和 39%（443/1144）。
即使在 NP 水平较低的亚组中，利钠肽仍然是 HFpEF 预后的重要生物标志物。当代 HFpEF 试验中纳入的 NP 单一、绝对阈值可能导致某些人口统计学和临床亚组代表性不足。
ClinicalTrials.gov 标识符：NCT00094302。
