Ανάλυση: Τα αντιυπερτασικά φάρμακα δεν καθιστούν τους ασθενείς πιο ευάλωτους στη λοίμωξη από κορωνοϊό

04/04/2020

Η πανδημία του κορωνοϊού έχει προκαλέσει πολλά ερωτήματα και έχει πυροδοτήσει την έρευνα για τους βιολογικούς μηχανισμούς διείσδυσης του ιού μέσα στα κύτταρα του ανθρώπινου οργανισμού.

Πρόσφατα δημοσιεύτηκαν στο έγκυρο περιοδικό Nature τα αποτελέσματα μια πειραματικής μελέτης του καθηγητή Φανγκ Λι, σύμφωνα με την οποία ο κορωνοϊός χρησιμοποιεί τους υποδοχείς του μετατρεπτικού ενζύμου της αγγειοτανσίνης (ACE 2) που εδράζονται στα κυψελιδικά κύτταρα των πνευμόνων. Ουσιαστικά οι ερευνητές διατείνονται ότι οι υποδοχείς ACE 2 αποτελούν τον «Δούρειο Ίππο» δια μέσω του οποίου ο κορωνοϊός διεισδύει μέσα στα ανθρώπινα κύτταρα και εν συνεχεία πολλαπλασιάζεται με ταχείς ρυθμούς. Στους ασθενείς που νοσούν αν και προεξέχουν τα συμπτώματα από το αναπνευστικό σύστημα, ιδίως πνευμονία και κατ΄επέκταση βαρεία αναπνευστική ανεπάρκεια, εντούτοις συχνά καταγράφονται μυοκαρδίτιδες, αρρυθμίες και νεφρική ανεπάρκεια, ευρήματα που σχετίζονται με την εκτεταμένη δράση του ACE 2.

Όμως τι είναι το ΑCE και ποιος είναι η βιολογική του δράση;

Στον ανθρώπινο οργανισμό υπάρχουν πολλαπλοί νευρο-ορμονικοί μηχανισμοί ρύθμισης της αρτηριακής πίεσης και της διατήρησης ισορροπίας υγρών και ηλεκτρολυτών. Ο βασικότερος μηχανισμός είναι το σύστημα ρενίνης-αγγειοτενσίνης-αλδοστερόνης.

Η ρενίνη παράγεται στους νεφρούς και μετατρέπει το αγγειοτενσινογόνο σε αγγειοτενσίνη Ι (δεκαπεπτίδιο). Εν συνεχεία το μετατρεπτικό ένζυμο της αγγειοτενσίνης (ACE) μετατρέπει την αγγειοτενσίνη Ι σε αγγειοτενσίνη ΙΙ (οκταπεπτίδιο).

Η αγγειοτενσίνη ΙΙ δρα ως ορμόνη που προκαλεί:

α) σύσπαση των αγγείων με αποτέλεσμα αύξηση της αρτηριακής πίεσης.

β) απελευθέρωση της αλδοστερόνης από τα επινεφρίδια. Η αλδοστερόνη προκαλεί κατακράτηση νατρίου και υγρών και κατά συνέπεια αυξάνει την αρτηριακή πίεση.

Tη δεκαετία του ’80 αναπτύχθηκαν οι αναστολείς του μετατρεπτικού ενζύμου της αγγειοτανσίνης (α-ΜΕΑ), ισχυρά και αποτελεσματικά φάρμακα που αποτέλεσαν επανάσταση στη θεραπεία της υπέρτασης. Μέχρι τότε η αγωγή βασιζόταν στη χορήγηση μεγάλων δόσεων διουρητικών και σε κεντρικώς δρώντα φάρμακα (δρούσαν σε υποδοχείς του εγκεφάλου), που είχαν πολλαπλές παρενέργειες και δεν είχαν εφάμιλλη αντιϋπερτασική δράση.

Τη δεκαετία του ΄90 αναπτύχθηκαν οι αναστολείς των υποδοχέων της αγγειοτανσίνης ΙΙ (σαρτάνες), επίσης αποτελεσματικά και ασφαλή φάρμακα. Οι δύο παραπάνω κατηγορίες φαρμάκων δοκιμάστηκαν με μεγάλη επιτυχία και στη θεραπεία ασθενών με καρδιακή ανεπάρκεια, ιδίως όσων είχαν υποστεί εκτεταμένο έμφραγμα μυοκαρδίου.

Οι πρώτες επιδημιολογικές μελέτες από την πόλη Wuhan της Κίνας, από όπου ξεκίνησε η πανδημία, κατέδειξαν ότι το 60% περίπου των ασθενών που νοσηλευόντουσαν στις μονάδες εντατικής θεραπείας και το 60% των ασθενών που κατέληξαν λαμβάναν αντιϋπερτασικά φάρμακα, γεγονός που έχει πυροδοτήσει τον επιστημονικό διάλογο για την ασφάλεια των προαναφερθέντων φαρμάκων (α-ΜΕΑ και σαρτάνες).

Θα πρέπει να γνωρίζουμε ότι οι υποδοχείς ACE 2 έχουν συγγένεια μόνο κατά 42% με τους αντίστοιχους του ΑCE. Επιπρόσθετα το υπόστρωμα και η δραστικότητα των δύο ενζύμων διαφοροποιείται σημαντικά. Τέλος δεν είναι τεκμηριωμένο ότι τα φάρμακα αποκλείουν τους υποδοχείς ACE 2 που εδράζονται στους πνεύμονες.

Δεν θα πρέπει να λησμονούμε το γεγονός ότι οι ασθενείς που λαμβάναν αντιϋπερτασικά συνηθέστερα έχουν συνοσηρρότητες (π.χ. διαβήτης) ή πιθανόν έχουν υποστεί στο παρελθόν έμφραγμα μυοκαρδίου-αγγειακό εγκεφαλικό επεισόδιο.

Πάντως ακόμη δε γνωρίζουμε αν η υπέρταση είναι πραγματικός παράγοντας κινδύνου (ανεξάρτητα από την ηλικία) για την ανάπτυξη της λοίμωξης από κορωνοϊό ή ένας παράγοντας που καθορίζει τη σοβαρότητα της ασθένειας. Δεν υπάρχουν κλινικά δεδομένα για να υποστηριχθεί ότι η λήψη α-ΜΕΑ/σαρτατών αυξάνει τον κίνδυνο και ούτε επιστημονικά δεδομένα τεκμηριώνουν μία σαφή συσχέτιση.

Το μόνο βέβαιο είναι ότι το ACE 2 αποτελεί σαφή θεραπευτικό στόχο και ήδη διεξάγεται κλινική μελέτη στην Κίνα με χορήγηση ανασυνδυασμένου ΑCE 2 από ανθρώπινα κύτταρα.

Με βάση τα παραπάνω, στην τρέχουσα φάση τόσο η Ελληνική Καρδιολογική Εταιρεία (ΕΚΕ) όσο και η Ευρωπαϊκή Καρδιολογική Εταιρεία (ESC) αλλά και η Αμερικάνικη Καρδιολογική Εταιρεία (ΑΗΑ)  δεν συνιστούν διακοπή ή αλλαγή των αντιϋπερτασικών φαρμάκων, τονίζοντας ότι είναι αναγκαία περαιτέρω έρευνα για την επίδραση της υπέρτασης και της αντιϋπερτασικής θεραπείας στην έκβαση των ασθενών που μολύνθηκαν από κορωνοϊό.

Ειδικότερα η διακοπή της θεραπείας σε ασθενείς με καρδιακή ανεπάρκεια ή ιστορικό εμφράγματος μυοκαρδίου εγκυμονεί κίνδυνο απορρύθμισης και δυσμενούς έκβασης.

Επισημαίνεται ότι ομάδες υψηλού κινδύνου σε περίπτωση λοίμωξης από κορωνοϊό θεωρούνται:

α) ηλικιωμένοι ασθενείς

β) ανοσοκατασταλμένοι ασθενείς (π.χ. καρκινοπαθείς, υπό κορτιζόνη, αυτοάνοσα νοσήματα).

γ) καρδιαγγειακά νοσήματα (ιδίως καρδιακή ανεπάρκεια, μη ρυθμιζόμενος σακχαρώδης διαβήτης σε συνδυασμό με άλλα νοσήματα)

δ) ασθενείς με χρόνια αποφρακτική πνευμονοπάθεια.

Συνοψίζοντας, τα τρέχοντα επιστημονικά δεδομένα συγκλείνουν στη συνέχιση της φαρμακευτικής αγωγής με αντιϋπερτασικά φάρμακα (α-ΜΕΑ, σαρτάνες) τόσο στους ασθενείς που νοσούν από κορωνοϊό όσο και στους ασθενείς υψηλού κινδύνου.

* Χρήστος Καϊρης, Καρδιολόγος, Δράμα -chriskairis@hotmail.com
* Γιάννης Γουδέβενος, Καθηγητής Καρδιολογίας, Πρόεδρος της Ελληνικής Καρδιολογικής Εταιρείας – igoudev@gmail.com

Πηγή: kathimerini.gr

Expert Opinion: “Crazy for Ketones” – The Ketogenic Diet in Athletes: Variable Effects on Athletic Performance with Potential for Cardiovascular Harm

01/04/2020
Tamanna Singh, MD, FACC

Athletic performance and physique have been closely associated with diet and nutrition for ages. From the high-carbohydrate, predominantly vegetarian diet of gladiators, warriors referred to as hordearii meaning “barley men,” to the creation of Gatorade in 1965, there is a countless number of diet plans touted as ideal for maximizing athletic performance.^[1,2] One such diet is the ketogenic diet, increasingly favored by many athletes. Despite its growing recognition, in my opinion, I do not recommend athletes follow this diet due to the high variability in performance results and its capacity to cause detrimental cardiovascular effects.

Traditional fueling strategies have emphasized high carbohydrate utilization for maximal athletic performance in endurance sports. However, in recent years, the ketogenic diet has grown in popularity due to reported benefits from reducing carbohydrate availability and maximizing fatty acid activation as the predominant fuel source for exercise.^[3] The original ketogenic diet is centered upon 75-80% fat intake, 15% protein, and less than 5% carbohydrates per day. This anticipates that glucose reserves will be depleted after as little as five days, thus halting normal fat oxidation and glucose supply to the brain and central nervous system and leading to the accumulation of ketone bodies.^[4,5]

Although there are no long-term studies comparing the effects of ketogenic to high carbohydrate diets on athletic performance, conclusions from short-duration studies are mixed. One study examining the effects of high-fat and high-carbohydrate diets on metabolism and athletic performance in endurance cyclists showed that high-fat conditions over a 2-week period were associated with greater lipolysis and fuel availability, lower plasma insulin concentration before exercise, and a 2.5 to 2.9-fold significant increase in fat-oxidation rates. Additionally, power increased by 2% for every 10% energy increase in fat, though this result was not statistically significant.^[6] In contrast, oxygen demand at a specific speed in elite race walkers, who were adapted to a ketogenic low carbohydrate-high fat diet over 3 weeks, increased and effectively negated the significant improvement in oxygen consumption.^[7] Ultimately, the variability in performance in athletes following a ketogenic diet is highly dependent upon exercise intensity with greater impairment seen in high intensity, anaerobic exercise. In Dr. Stephen Phinney’s 1980’s study of five well-trained cyclists following a high fat diet with significant carbohydrate restriction (<20 grams/day), their ability to exercise anaerobically was significantly impaired.^[8,9] While endurance training may enhance an athlete’s capacity for fat oxidation, the increase in fatty acid availability for fuel cannot compensate for the low muscle glycogen stores, which can subsequently impair exercise capacity.^[10]

An individual athlete generally decides his/her preference for sport nutrition based upon performance goals. However, as sports cardiologists, it is imperative that we discuss the longitudinal impact of specific diets on an athlete’s cardiovascular health, particularly since diets that increase cardiac risk may hinder future athletic performance. The ketogenic diet is predicated on high fat consumption for fat-adaptive fueling as well as increased protein consumption, with carbohydrate intake typically less than 30 grams per day.^[11] Consequently, the type of fat (saturated versus unsaturated) and protein (animal versus plant) can influence cardiovascular risk. While mitigating cardiovascular risk is important for athletes of all ages, masters athletes (age 35 years or greater) are particularly susceptible to greater risk of cardiovascular morbidity and mortality with ketogenic diets that incorporate high saturated fat and animal protein consumption. Additionally, athletes with a family history of premature coronary artery disease and myocardial infarction should also be counseled on reducing animal-based food sources to reduce saturated fat intake and inherently cardiac risk.

Not only does diet impact athletic performance, but it also provides a means to develop sport-specific body composition that supports the level of athleticism required. For instance, athletic performance in weightlifters is predicated upon building muscle mass, and thus the macronutrient composition (protein, fat, carbohydrate) of their diets is skewed towards high protein and low carbohydrate intake. Although a low carbohydrate-ketogenic diet shows benefit in achieving an optimal power-to-weight ratio without compromising lifting performance, the cardiovascular consequences persist depending upon food source (plant versus animal).^[12] American football linemen require an increase in both muscle mass and total body mass, often relying on heavy intake of all macronutrients, which is synonymous with increased caloric intake. Fat, being the most calorically dense macronutrient, is a key component to these athletes’ diet, and more often than not, saturated fat intake far outweighs unsaturated fat intake. In a study assessing dietary composition in 88 National Collegiate Athletic Association (NCAA) Division III (DIII) football players, players consumed an excessive amount of saturated fat with dietary cholesterol intake three times greater than the recommended amount. Over 80% of football players consumed dairy products daily. Additionally, consumption of cardioprotective foods such as plant-based carbohydrates, fiber, and unsaturated fats was quite low.^[13]

An athlete’s biological age is also important for determining the appropriate composition of macronutrients needed to support performance goals within the confines of growth and changes in body composition with aging. For instance, adolescent athletes require energy deposition in growing tissues and energy expenditure for tissue synthesis. Protein intake must remain adequate to avoid its use as an energy substrate. Carbohydrate intake must also be sufficient to accommodate the wide variability in competition intensity, frequency, and format and to fuel athletes who participate in multiple different sports of varying intensities.^[14] Upon reaching age 20-30 years, muscle mass and strength peaks and then begins to decline at 40-50 years. As a result, the dietary needs for optimal athletic performance in masters athletes is quite different from that of adolescents and is influenced by gender. Male masters athletes require greater total protein intake (1.6-1.8 g/kg daily) to maintain strength and power while women require 25% less intake due to a decrease in amino acid oxidation that is mediated by estrogen. As females exit menopause, protein intake requirements become similar to male counterparts. Carbohydrate supplementation of greater than 8.0 g/kg daily is also beneficial to masters athletes, particularly in female masters endurance athletes where carbohydrate intake appears to be reduced and can contribute to the development of syndromes associated with low energy availability (e.g. Relative Energy Deficiency in Sports, RED-S) that inevitably lead to poor athletic performance and increased risk of physical and multisystem injury.^[14]

A significant number of animal and human studies use saturated fats as the predominant fat source when examining effects of the ketogenic diet. The primary storage units for body fat include intramuscular triglyceride, blood lipids, and adipose tissue.^[10,11] There is a general consensus that diets high in saturated fat contribute to increases in LDL-C concentration and overall cardiovascular mortality.^[15,16] Thus, a ketogenic diet dependent upon high saturated fat intake will likely contribute to dyslipidemia, a well-known cardiovascular risk factor and mediator for progressive atherosclerosis and cardiac events.^[11] In a meta-analysis of 13 studies investigating cardiovascular risk management and weight loss in a very low carbohydrate ketogenic diet (maximum of 50 grams of carbohydrates daily) versus a low-fat diet (less than 30% of daily energy from fat), individuals following a very low carbohydrate ketogenic diet over a 12-month period had significantly increased LDL-C and HDL-C levels.^[17] An additional meta-analysis comparing low-carbohydrate to low-fat diets revealed similar findings with increased LDL-C levels, despite weight loss, suggesting that ketogenic diets may not be beneficial to individuals with heightened cardiovascular risk.^[18] Fortunately, replacing saturated fat with polyunsaturated fat is associated with lower risk of cardiovascular disease. In an analysis of a summed cohort of 222,234 adults in the Health Professionals Follow-Up, Nurses’ Health Study and the Nurses Health Study II, a 24% reduction in cardiovascular disease risk was seen by replacing 5% of energy intake from dairy fat with polyunsaturated fat.^[19] An additional meta-analysis investigating low- vs high-fat diets and effect on lipid profiles also revealed that lower saturated fat intake was associated with lower LDL-C levels.^[20]

In addition to increased fat consumption, the proportion of protein for total energy intake is also increased. With a near-complete elimination of carbohydrates, pure protein sources are limited to animal sources or synthetic protein powder, as most plant proteins are compound macronutrients. The source of protein – whether animal or plant – dictates cardiovascular risk. In a prospective cohort study of 131,342 health care professionals, higher animal protein intake was associated with significantly higher cardiovascular disease mortality, whereas higher plant protein intake was associated with lower cardiovascular mortality. In a subgroup analysis comparing individuals with healthy lifestyle behaviors to those with unhealthy behaviors, there was greater association between animal protein consumption and increased cardiovascular risk with the unhealthy group.^[21]

By markedly reducing carbohydrate intake in ketogenic diets, foods rich in complex carbohydrates such as fruits, vegetables, and legumes are virtually eliminated from consumption. Authors of a meta-analysis of eight prospective studies assessing legume consumption within the Mediterranean diet showed significant reduction in cardiovascular disease outcomes, including cardiovascular mortality, coronary artery disease, myocardial infarction, and stroke.^[22] Additional meta-analyses and randomized controlled trials demonstrated that legume consumption was inversely associated with coronary artery disease risk, improved glycemic control by reducing postprandial blood glucose, reduction in LDL-C, and reduction in systolic blood pressure.^[23,24]

Whether we, as sports cardiologists, can extrapolate data collected in non-athletic populations to competitive athletes and highly recreational individuals, is debatable. However, the evidence demonstrating benefits and harm of specific sources of macronutrients appears to be quite generalizable. While a ketogenic diet may be favorable for maximizing fatty acid utilization in prolonged endurance sports, the incorporation of healthy, cardiovascular risk-reducing plant-based complex carbohydrates and plant protein is compromised for the sake of performance. The short-term effects of this dietary commitment may not lead to a measurable increase in cardiovascular risk. However, while there is a paucity of longitudinal investigations of the ketogenic diet and cardiovascular risk in athletes, I suspect that consuming a ketogenic diet as a long-term strategy to maximize athletic performance increases the risk of progressive atherogenesis and poor cardiovascular outcomes that would ultimately impede athletic performance. Should an athlete still aspire to incorporate a ketogenic diet to maximize athletic performance, I recommend using a shared-decision making model to generate a list of macronutrient sources that do not increase risk of cardiovascular disease (Figure 1).

Figure 1

Dietary sources of macronutrients in a ketogenic diet, “heart-healthy” diet, and combination ketogenic-cardiac diet (DI = daily intake).12

Summary of Author Recommendations:

• Sports cardiologists should regularly inquire about an athlete’s nutritional preference to determine whether the diet type supports an athlete’s energy demands without compromising systemic and cardiovascular health.
• Age, gender, and sport-type influence an athlete’s dietary needs.
• The ketogenic diet is not a favorable choice in athletes who prefer to consume saturated fats and predominantly animal-based protein, as evidence suggests both of these forms of macronutrients are associated with increased risk of developing cardiovascular disease.
• Athletes whose dietary intake predominantly consists of unsaturated fats and plant-based proteins may be able to follow a ketogenic diet to meet performance goals in endurance and weight-lifting events, provided that they understand the limitations this diet poses in high-intensity/anaerobic-metabolic states of exercise.
• A shared-decision model is ideal when discussing diet types and macronutrient sources that will best support athletic performance and reduce cardiovascular disease risk.

Πηγή: medscape.com

Effects of Omega-3 Fatty Acid Supplements on Arrhythmias

2020
Sarah Parish, DPhil; Marion Mafham, MRCP, MD; Alison Offer, PhD; Jill Barton; Karl Wallendszus, MSc; William Stevens, PhD; Georgina Buck, MSc; Richard Haynes, DM; Rory Collins, MBBS, MSc; Louise Bowman, MD, MRCP; Jane Armitage, MRCP, MFPH

For several decades there has been interest in the possible role of omega-3 fatty acids (FAs) in the prevention of cardiovascular disease and the possibility that they have antiarrhythmic effects. Higher consumption of fish (which contains the long-chain omega-3 FAs, eicosapentaenoic acid, and docosahexaenoic acid) is associated with lower risks of coronary heart disease events, and particularly of cardiac deaths in observational studies, but meta-analyses in 2018 of randomized trials of &frac12; to 2 g omega-3 FA supplementation for a mean of 4 to 5 years failed to show convincing benefits on cardiovascular outcomes.^[1] However, recently, the REDUCE-IT trial (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial) of a daily dose of 4 g icosapent ethyl (a purified form of eicosapentaenoic acid) in participants with high triglycerides reported a highly statistically significant 25% proportional reduction in various cardiovascular outcomes.^[2] The results in both low and high dose large trials are consistent with a pro rata to dose reduction in coronary heart disease events of 7% to 8% per 1 g eicosapentaenoic acid + docosahexaenoic acid supplementation.^[1,2] However, in REDUCE-IT,^[2] supplementation was also associated with a nominally statistically significant (without adjustment for multiple comparisons) ≈50% increase in hospitalization for atrial fibrillation (AF) or flutter. It is not clear whether this excess is reflected in the low dose trials.^[2] In ASCEND (A Study of Cardiovascular Events in Diabetes), we previously reported the effects of omega-3 FA on participant-reported arrhythmia adverse events, but here we report more comprehensively on AF and other arrhythmias, using additional data extracted from linked electronic health records.^[3]

ASCEND was a large mail-based randomized trial that assessed the effect of daily 1 g omega-3 FA supplementation (containing 0.84 g eicosapentaenoic acid + docosahexaenoic acid) on the risk of serious vascular events in people with diabetes mellitus but without known atherosclerotic cardiovascular disease (and, in a 2×2 factorial design, also the effects of low-dose aspirin; current Controlled Trials number, ISRCTN60635500; ClinicalTrials.gov number, NCT00135226.).^[3] The protocol was approved by the North West Multi-centre Research Ethics Committee and all of the participants provided written informed consent. Anticoagulant use at randomization was an exclusion criterion (because of the aspirin comparison), and this would have excluded most people with known AF (as anticoagulant use is recommended in AF). The main results on omega-3 FA supplementation, reported previously, showed no significant effect on the primary outcome.^[3] This investigation includes added data extracted from electronic record linkage to hospital episodes, available for 97% of participants both during the trial and for 14 years before randomization.

Arrhythmia outcomes were defined based on either hospitalizations or serious episodes reported by the participants during follow-up or from International Classification of Diseases, Tenth Revision diagnoses or OPCS Classification of Interventions and Procedures, Version 4 procedure codes in the electronic data. AF diagnoses in hospital episodes before randomization were used to define previously known AF. Arrhythmia outcomes considered are AF (among participants without any previously known AF) and nonfatal ventricular arrhythmia. We only considered nonfatal ventricular arrhythmias, with survival to the next day, because we could not reliably ascertain all arrhythmias contributing to death, and it was not possible to determine which cardiac arrests without resuscitation had involved an arrhythmia. Therefore, we also consider the outcome cardiac deaths overall, which would include sudden deaths attributable to fatal cardiac arrhythmias (see Arrhythmia Outcome Definitions on the ASCEND study web page: https://ascend.medsci.ox.ac.uk/professionals). Statistical methods are as used in the main study report.^[3] P values <0.01 were considered statistically significant in this secondary analysis.

Among 15 480 participants randomized in ASCEND, less than 1% had a previous hospital admission with an AF diagnosis. Among the remaining 99%, AF was recorded from either electronic health records or participant reports in 1177 participants, compared with 287 by self report alone. AF occurred in 7.7% of participants in the omega-3 FA group and in 7.6% in the placebo group, with a nonsignificant rate ratio (RR) of 1.02 (95% CI, 0.91 to 1.15). A non-fatal ventricular arrhythmia was recorded in nonsignificantly more participants in the omega-3 FA group than in the placebo group (81 vs 54; RR, 1.49; 95% CI, 1.06 to 2.09; P=0.02). Most (106/135) of the nonfatal ventricular arrhythmias required intervention (resuscitation, ablation, or implantable cardioverter defibrillator); sensitivity analyses restricting to these ventricular arrhythmias yielded a similar RR of 1.90 (95% CI, 1.30 to 2.77). Cardiac death occurred in fewer participants in the omega-3 FA group than in the placebo group (1.7% vs 2.2%; P=0.04).

The 47% proportional excess of hospitalization for AF observed in REDUCE-IT with 4-g daily supplementation corresponds to a 10% (95% CI, 3% to 18%) proportional excess per 1 g, and 2 other of the 10 large low-dose trials have reported on AF and found nonsignificant positive associations with hospitalization for AF (Figure).^[2,4,5] The association in the low-dose trials, including ASCEND, in combination is not statistically significant, but does not exclude the level of effect per gram seen in REDUCE-IT.

Figure.

Effects of omega-3 fatty acid supplementation on atrial fibrillation in large trials.
The atrial fibrillation (AF) outcomes were: GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca – Heart Failure),⁴ among participants without ECG evidence of AF at randomization, AF in the ECGs taken at each visit during the trial or an event between visits causing or worsening heart failure/hospitalization; Risk and Prevention Study,⁵ hospitalization for AF; ASCEND (A Study of Cardiovascular Events in Diabetes), new onset of AF; REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial),² hospitalization for AF or atrial flutter. The risk ratio and CI in REDUCE-IT were estimated from the reported percentages getting the outcome in each group and the P value (3.1% vs 2.1%, supplementation vs placebo, P=0.004). DHA indicates docosahexaenoic acid; and EPA, eicosapentaenoic acid.

In conclusion, evidence from large trials now suggests that omega-3 FA supplementation may have a dose-related protective effect on coronary events. However, systematic reporting of arrhythmia outcomes in existing and future trials is required to clarify whether supplementation also has any adverse effects on nonfatal arrhythmias.

Πηγή: medscape.com

E3: A ‘Glimmer of Hope’ and Renewed Concerns Over E-Cigarettes

01/04/2020
Patrice Wendling

The first large North American study to directly test the question of whether e-cigarettes help tobacco smokers quit suggests an early benefit but with little long-term data to allay growing safety concerns.

The Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation (E3) trial was conducted at 17 Canadian centers and randomly assigned 376 adults who had smoked for 35 years to individual counseling alone or with an e-cigarette with refill cartridges containing nicotine or cartridges without nicotine.

Progress among the participants (mean age, 52 years; 53% male) was checked during three phone calls and two clinic visits that included carbon monoxide testing.

At the 12-week visit, 22% of participants assigned nicotine e-cigarettes quit smoking traditional cigarettes, compared with 9% given counseling alone. With non-nicotine e-cigarettes, the proportion fell in between at 17%.

“We asked subjects at 12 weeks whether they thought they got an e-cigarette with or without nicotine and only 50% of them were right in both arms; they couldn’t tell,” lead author Mark J. Eisenberg, MD, McGill University, Montreal, told theheart.org | Medscape Cardiology. “It’s interesting, just having that e-cigarette helped a lot of people give up cigarettes, at least for 12 weeks.”

Even with the use of pharmacologic or behavioral therapy, well over two-thirds of those attempting to quit return to smoking within 1 year, he noted during his late-breaking presentation at the virtual American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.

Indeed, 91% of the participants had previously tried to quit, 80% had used aids, such as smoking-cessation medications or behavioral therapy, and 36% had already tried e-cigarettes.

Compared with counseling alone, the absolute risk difference in 12-week quit rates was 12.8% with nicotine e-cigarettes (relative risk [RR], 2.4; 95% CI, 1.3 – 4.6) and 8.2% with non-nicotine e-cigarettes (RR, 1.9; 95% CI, 1.0 – 3.8).

The researchers also measured continuous abstinence, in which participants were counted as having failed if they reported smoking even one puff of cigarette at week 1. By this more rigorous measure, the nicotine and non-nicotine e-cigarette groups did slightly better than the counseling-alone group at each time point, with rates reaching 5%, 3%, and 1%, respectively, at 12 weeks, Eisenberg said.

The average number of cigarettes smoked per day fell from 21 at baseline to 14 at 12 weeks in the counseling-alone group, 10 in the non-nicotine e-cigarette group, and eight in the nicotine e-cigarette group. As expected, dropout was more common in the counseling-only group because many people enrolled hoping to get e-cigarettes, he noted.

Given that relapse is known to be very common after quitting, panelist Nancy Rigotti, MD, Massachusetts General Hospital, Boston, observed that the norm for smoking-cessation trials is to present at least 6 months and ideally 12 months of follow-up to ensure the intervention leads to permanent cessation.

“Twelve weeks is really the ‘end of treatment’ point,” she said.

E3 was planned to run for 52 weeks, but a prolonged e-cigarette manufacturing delay forced enrolment to be halted at 77% of the planned enrollment and the timing of the primary end point was changed to 12 weeks, given the reduction in power, Eisenberg explained. Longer-term 6- and 12-month data will be assessed to “determine if the benefits we saw persist over time.”

Safety Data

At 12 weeks, there were few serious adverse events, which were adjudicated and determined to be unrelated to the interventions, Eisenberg said. They were one COPD exacerbation in the nicotine e-cigarette group; appendicitis, neoplastic cecal lesion, myocardial infarction, chest pain, and epistaxis (one each) in the non-nicotine e-cigarette group; and one critical limb ischemia and one urinary tract infection in the counseling group.

Still, clinicians are struggling over whether to recommend e-cigarettes for smoking cessation. In addition to reports of e-cigarette or vaping-associated lung injury (EVALI), data are emerging suggesting increased risks for pulmonary disease and cardiovascular events.

The devices used in the study were closed units, so it was not possible to adulterate the liquid with vitamin E acetate or other additives, Eisenberg said in an interview. E-cigarette liquid can expose users to ultrafine particles, aldehydes, but levels are lower than in traditional cigarettes, he noted.

“I’m pretty sure how the e-cigarette makers will tout this study and that concerns me,” Martha Gulati, MD, chief of cardiology at the University of Arizona College of Medicine, Phoenix, told theheart.org | Medscape Cardiology. “They will say they help people quit and they’re going to tell us that’s evidence enough.

“This is a small study, it’s only 12 weeks, it doesn’t answer the question that it [an e-cigarette] is effective in helping people quit, nor does it address anything about safety,” she added. “The long-term ability of this to help people quit is one part, and the safety is, of course, a second and equal part. Because if something makes you quit but its gonna kill you in a different way, we need to know that too.”

Gulati said she strongly believes the US Food and Drug Administration (FDA) should regulate e-cigarettes. E-cigarettes are recommended as a smoking-cessation tool in the United Kingdom, but the ACC and American Heart Association have yet to endorse their use because of the lack of data, she noted.

Speaking to theheart.org | Medscape Cardiology, preventive cardiologist Pamela Morris, MD, Medical University of South Carolina, Charleston, said the study offers a “glimmer of hope,” but that she shares Gulati’s concerns about how the results will be interpreted.

“If I knew I had a highly regulated product that had controlled manufacturing and a good definition of nicotine content and the other substances that are within the suspension of the nicotine, I could be someone who would be optimistic that it provides a potential tool, ultimately,” she said. “But I think we have to be careful not to let this be the wild, wild West, and that is what I’m afraid of — that headlines could overhype these things.”

Morris also called for more regulation, beginning with a clear definition of what constitutes an e-cigarette.

“We’re going to have to define what is an e-cigarette because it’s not any product out there and any product out there used any way you please,” she said. “Then we’re also going to have to weigh it in the balance of the risk to youth and the risk to nonsmokers who may be tempted to take these products.

“There’s some reassuring information that there’s safety and benefit with a controlled product in a controlled setting along with counseling and careful supervision,” she said. “But we need the long-term data and it all needs to be balanced against all of the other concerns.”

As part of the panel discussion, Rigotti also pointed out that e-cigarettes are a “moving target” and that their design is rapidly evolving. The best-selling products are now the pod mods sold by Juul Labs and others, which deliver a higher dose of nicotine and do so more rapidly than the second-generation device that was tested.

As such, might the results be different if a Juul e-cigarette were tested, she asked.

“My father was a doctor; he told me he liked to see 10 different studies in 10 different patient populations with 10 different products before he would consider accepting the results, so I think that’s true here,” Eisenberg replied.

The researchers actually contacted Juul when this began, “but they didn’t even want to talk to us to do a trial,” he said.

When interviewed, Eisenberg said he’d like to see a smoking-cessation trial comparing varenicline (Chantix) plus e-cigarettes, given the data from the EAGLES trial. And in the meantime?

“I tell my patients: ‘Look, e-cigarettes are not safe, they’re just much safer than conventional cigarettes’,” Eisenberg said.

“Personally, I think they should only be used by people who are trying to quit smoking,” he said. “I don’t think they should be used by youth; I don’t think they should be used by people who have never smoked. In fact, I could conceive of a situation where e-cigarettes were only prescribed by physicians for smoking cessation, in the same way we prescribe varenicline, bupropion, or a nicotine patch.”

As part of an ongoing lawsuit, e-cigarette manufacturers have until May 12 to apply to the FDA and demonstrate a public-health benefit in order to keep their products on the market. Because of the COVID-19 pandemic, however, the FDA has asked the court to extend that deadline until September 9, according to a statement issued today by several professional medical groups that are plaintiffs in the lawsuit. Last week, the FDA told Bloomberg News that vaping may leave users with underlying health conditions at higher risk for serious complications from COVID-19.

E3 was sponsored by McGill University . Coauthor Wilderman received financial compensation from Pfizer for his involvement in a smoking-cessation study using varenicline. The other authors, Gulati, and Harris reported having no relevant conflicts of interest.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC): Abstract 411.08. Presented March 30, 2020.

Πηγή: medscape.com

Vitamins and Supplements Are a Waste of Money

09/07/2019
F. Perry Wilson, MD, MSCE

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson.

Thirty billion dollars. That’s how much Americans spend every year on vitamins and supplements. And according to the most comprehensive analysis of their effects, most of that money is being wasted.

The “umbrella review,” appearing in the Annals of Internal Medicine,[1] is a comprehensive reporting of randomized trials of vitamins and supplements that examined their effects on cardiovascular disease and overall mortality.

Including only randomized trials was a great choice. Observational studies of vitamin and supplement usage are plagued by what’s known as “healthy user bias”: Individuals who choose to take vitamins often engage in other healthful behaviors. Time and again, vitamins that looked promising in observational studies failed in large randomized trials. I’m looking at you, vitamin D.

Now we have all of the best data surrounding vitamins and supplements in one place, which allows me to say the following: There is no high-quality evidence that any vitamin or supplement has a beneficial effect on overall mortality.

But okay, I’ll give you the details.

The analysis included studies of 24 different interventions—I’ve listed most of them here—comprising 277 randomized trials and nearly a million patients. And, basically, bupkis.

The only intervention that had even moderate-quality evidence for protection against all-cause mortality was reducing salt intake, which, frankly, doesn’t sound like a vitamin or supplement to me.

To give fair play to the other findings, there was low-quality evidence that omega-3 fatty acids might protect against myocardial infarction and heart disease, and that folic acid might protect against stroke. There was moderate-quality evidence that a combination of calcium and our old friend vitamin D increased the risk for stroke.

But all of these effects were pretty small.

Why? Well, let’s remember that vitamins were, by and large, identified via their deficiency syndromes. We know that vitamin C is vital for life because without it, people get scurvy. But there has never been much rationale as to why a super-intake of any of these chemicals would give super-benefits to health.

To be fair, this is only looking at mortality and cardiovascular outcomes. It remains possible that vitamins and supplements might improve subjective quality of life. But you know what else improves quality of life? Money. And based on this study, you might want to save yours when you’re walking down the vitamin aisle.

Πηγή: medscape.com