Table 6.

Study characteristics, urine biomarker methods, and qualitative results of recent prospective cohort studies of sodium intake and health outcomes, by type of cohort^a

Study population and follow-up				Urine biomarker used to assess Na intake					Health outcome	Association with Na intake
First author (reference)	N	Age (y)	Follow-upb (y)	Type	Duration of Na assessmentc (d)	Number of specimens per person	Adjustment/equation used to estimate individual sodium intake	Na intake levels assessed (g/d)
General population
Cook (26)	2,275	30–54	10–15	24 h	547–1,460	1–7e	Mean of 1–7 measured 24-h urine Na, Na/K, Na/Cr excretion	q 1.0 <2.3 2.3–<3.6 3.6–<4.8 (ref) ≥4.8	CVD CVD	P* N
Joosten (72)	7,543	28–75	10–11	24 h	2 (48 h)	2	Mean of 2 measured 24-h urine Na excretions	q 1.0, sex-specific quartiles, lowest (ref)	CHD	N (total) P (HTN) P (NT- proBNP level >median)
O’Donnell (113)	101,945	35–70	3.7, 1.7–2.7f	Spot, fasting, morning	1 (30–90 in 448)g	1 (up to 2 in 448)g	Estimated 24-h urine Na and K excretion, Kawasaki prediction equationsh	<3.0 3.0–3.9 4–5.9 (ref) 6–6.9 ≥7.0	CVD CVD + death Total death Stroke	J J J J
Stolarz-Skrzypek (136)	3,681	41i	7.9	24 h	1	1	No adjustment	Tertiles	Stroke CHD CVD CVD death Total death	N N N I N
Geleijnse (48)	7,983	55+	5.0	Overnight, timed	1	1	Standardized to 24 hours using recorded collection time, Na, and Na/K	1 SD Na (1.6 g), 1 unit Na/K ratio	MI Stroke CVD death Total death	N N N N
Tuomilehto (142)	2,436	25–64	8–13	24 h	1	1	Adjusted for regression dilution bias using data from other studies	q 2.3 g	Stroke CHD CVD death Total death	N P P P
Pre-existing disease
Cardiovascular disease or diabetes mellitus
O’Donnell (114)	28,880	67i	4.7	Spot, morning, fasting	1 (up to 730 on 2,625)j	1 (up to 2 on 2,625)j	Estimated 24-h urine Na and K excretion using Kawasaki prediction equationsh	<2.0 2.0–3.9 4–5.9, ref 6–8 >8	CVD/CHF Stroke MI CHF CVD death Total death	J N(L), P(H) N(L), P(H) J J N(L), P(H)
Diabetes mellitus
Thomas (139)	2,807	39i	10	24 h	1	1	No adjustment	<2.3 2.3–4.3 (ref) >4.3	Total death ESRD	J I
Ekinci (36)	638	64i	9.9	24 h	Up to 365k	1–5k	Mean of 1–5 measured 24-h urine Na excretions	q 2.3	CVD death Total death	I I
Chronic heart failure
Lennie (87)	302	23–97	1	24 h, timed	1	1	No adjustment	>3 g ≤3 g	Cardiac event	I (I/II) P (III/IV)
Son (133)	232	40–87	1	24 h, timed	1	1	No adjustment	<3.0 ≥3.0	Cardiac event	P
Chronic kidney disease
McQuarrie (104)	448	51	1	24 h	385	Up to 2 on 154	Na/Cr ratio	<16.0 ≥16.0 Stratified by albumin excretion	Total death RRT RRT + death	P* N P*
Vegter (144)	500	18–70	4.25	24 h	796l	5.4l	Mean of multiple measured 24-h urinary Na/Cr ratio, mEq/g	<2.9m 2.9–5.75 >5.75	ESRD	P

^aAbbreviations: CHF, chronic heart failure; CHD, coronary heart disease; Cr, creatinine; ref, referent (comparison) group; CVD, cardiovascular disease; ESRD, end-stage renal disease; H, high sodium; HTN, hypertension; I/II or III/IV correspond to New York Heart Association class of heart failure, III/IV is advanced; K, potassium; L, low sodium; MI, myocardial infarction; N, number of participants; Na, sodium; NT-ProBNP, N-terminal pro-B-type natriuretic peptide; RRT, renal replacement therapy.

^bFollow-up time from baseline Na assessment to outcome assessment in years.

^cDuration in days from first to last time Na is assessed, i.e., the duration of Na exposure period.

^dPattern of association with sodium intake: P, a direct positive association; N, null or not statistically significant; J, J-shaped association increased risk at low and high sodium intake; I, inverse association;

^*some groups or analyses the association is not significant, parentheses indicate subgroups related to the association.

^eMedian of five measurements per person over a period of 18 to 48 months (26).

^fPost hoc sensitivity analysis excluding people with CA at baseline; with CVD, CA at baseline or follow-up; DM, who were prescribed CVD medications or who were smokers; with CVD events in years 1 and 2 (113).

^gIn a separate analysis, investigators reported within-person day-to-day variability was adjusted based on a <1% sample of 448 participants with a second spot urine collected at an unspecified time after the first measurement (113).

^hKawasaki prediction equation for sodium is as follows: 24-h urinary Na = 23 × (16.3 × XNa^0.5), where XNa = [spot Na (mmol/L)/spot Cr (mg/dl) × 10] × [Pr24hCr (mg/day)] (113, 114).

ⁱMean age as range is not reported (36, 39, 114, 136).

^jIn a subsample of 9% of study participants, a second spot urine was measured two years after the first and used to adjust sodium intake for within-person day-to-day variability in secondary sensitivity analysis (114).

^kOne to five (median two) 24-hour urine collections were used to assess average sodium excretion for each individual. The timing of measurements were not specified but occurred anytime during the year 2001 (36).

^lTwenty-four-hour urine was collected at baseline, and then at 3 months, 6 months, and every 6 months thereafter for a period of 26.2 months. The minimum and maximum number of measures was not specified, but the average number of collections per person was 5.4 (144).

^mBased on <100 mEq/g, 100–200 mEq/g, and >200 mEq/g, which according to the authors is about 125 and 250 mEq Na/d (144).