Dissertation committee:
Αθανάσιος Πρωτογέρου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αθανάσιος Τζιούφας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Γιαννακούλια, Καθηγήτρια, Τμήμα Επιστήμης Διαιτολογίας-Διατροφής, Χαροκόπειο Πανεπιστήμιο
Χαράλαμπος Βλαχόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Θεόδωρος Παπαϊωάννου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καλλιόπη Καράτζη, Επίκουρη Καθηγήτρια, Τμήμα Επιστήμης Τροφίμων και Διατροφής του Ανθρώπου, Γεωπονικό Πανεπιστήμιο Αθηνών
Καλλιόπη-Άννα Πούλια, Επίκουρη Καθηγήτρια, Τμήμα Επιστήμης Τροφίμων και Διατροφής του Ανθρώπου, Γεωπονικό Πανεπιστήμιο ΑΘηνών
Original Title:
Μελέτη της διατροφικής πρόσληψης νατρίου σε πληθυσμούς με αυξημένο καρδιαγγειακό κίνδυνο: α. συμπεριφορική και ποσοτική ανάλυση, β. σύγκριση των μεθόδων εκτίμησής της, γ. συσχέτιση με την υποκλινική αγγειακή βλάβη
Summary:
Subclinical vascular damage (SVD) [arteriosclerosis (arterial stiffening), arterial remodeling and atheromatosis (arterial plaques)] pre-exists decades before cardiovascular disease (CVD) onset and represents a non-invasive method to evaluate CVD risk. Worldwide, sodium (Na) intake is almost double than international recommendations and has been linked with CVD and death, although sometimes in a J-shape manner. Until today, the available data on humans regarding SVD and dietary Na remain limited, especially for particular types of SVD like atheromatosis. Moreover, accurate and easy to use methods for dietary Na assessment in population level are lacking.
The present study was conducted in medium-to-high CVD risk Greek populations (arterial hypertension, diabetes mellitus, chronic inflammatory/ autoimmune diseases, HIV) to:
(i) record and quantify dietary Na intake through all the available assessment methods [dietary methods (e.g., multiple 24h dietary recalls (24DR) and food frequency questionnaires (FFQ) and urinary methods (e.g., spot urine samples using different formulas and 24h urine collection (24UC)];
(ii) compare all the examined Na assessment methods regarding their accuracy versus the gold-standard 24UC;
(iii) design and develop a new more accurate dietary tool to record Na intake (FFQ, food items rich in Na and salt-related questions were added in a standard questionnaire (NaFFQ)) and to improve the existing dietary methods (discretionary Na quantification using salt-related questions or adding extra 15% in total Na intake);
(iv) investigate the association between dietary Na intake and major types of SVD in our cohort study, using state-of-the-art methods to record SVD biomarkers (tonometry to assess arterial stiffness using the cfPWV and b-mode ultrasonography to detect arterial plaques);
(v) as well as to investigate this association through a systematic literature review according to PRISMA criteria on 36 interventional and observational studies.
The present study led to the following findings:
(i) In 901 individuals (age: 52.4±13.8 years, 45.2% males) [Cohort A], mean dietary Na intake, recorded from two 24h dietary recalls was 2442.6±1317.5 mg/day for men and 1615.8±810.6 mg/day for women. In regard to the other Na assessment methods, in 122 high cardiovascular risk subjects (56.0±12.6 years; 55.7% males) [Cohort B], mean 24h Na excretion was 2810±1304 mg/day.
(ii) Spot urine methods overestimated the 24h Na excretion (bias range: -1781 to -492 mg) and were moderately correlated to 24UC (r=0.469-0.596, p≤0.01). Dietary methods underestimated the 24h Na excretion (bias range: 877 to 1212mg) and were weakly correlated with 24UC. The improved dietary methods underestimated the 24h Na excretion (bias range: 877 to 923mg).
(iii) The new NaFFQ presented the smallest bias (-290±1336mg) and the strongest correlation with 24UC (r=0.497, p≤0.01), but wide limits of agreement in Bland-Altman plots (-2909mg; 2329mg), like all the other methods did.
(iv) Regarding the association between arterial pathologies and dietary Na, females -but not males- at 3rd and 4th quartile of total Na intake (derived from food and discretionary salt) had significantly lower probability to present femoral plaques compared to those at 1st quartile (751.0±215.5 mg/day), even in the full-adjusted model [0.462(0.229-0.935), p=0.032 3rd quartile; 0.274(0.118-0.638), p=0.003 4th quartile] (Cohort A). On the contrary, male and female individuals at 3rd quartile had significantly higher probability to present arteriosclerosis (PWV>10 m/sec) compared to those at 1st quartile [1.991(1.047-3.785), p=0.036] (Cohort A).
(v) The systematic literature review led to the following observations regarding Na and SVD: (a) Although several studies exist, the evidence does not clearly support a clinically meaningful and direct (independent from blood pressure) effect of Na on arterial wall stiffening; (b) data regarding the association of dietary Na with arterial remodeling are limited, mostly suggesting a positive trend between dietary Na and arterial hypertrophy but still inconclusive; (c) as regards to atheromatosis, data are scarce and the available studies present high heterogeneity.
Overall, the present study indicates that very low Na intake is associated with: i) accelerated atheromatosis, verifying findings from animal models, providing a possible explanation of the modern epidemiology, and ii) lower arteriosclerosis, which is in line with previous human findings, therefore suggesting a diverging effect of Na in the two major arterial pathologies. Regarding dietary Na assessment, the present analysis found out that the existing methods exhibit poor accuracy. Further improvement of the newly developed NaFFQ could be promising for more accurate estimation of mean dietary Na intake in epidemiological studies. Further state-of-the-art studies must address the remaining controversies and gaps in knowledge as well.
