Accurate quantification of pulmonary perfusion ratio in children with congenital heart disease using partial volume corrected 4D flow cardiac magnetic resonance.

Background: In children with congenital heart disease (CHD), lung scintigraphy is the reference standard for evaluation of pulmonary perfusion. 4D flow CMR offers a non-ionizing alternative. Due to the intrinsic limitation in the spatial resolution, however, 4D flow may display clinically unacceptable differences compared to the reference standard. This case study aims to highlight the importance of correcting for such partial volume errors to accurately evaluate pulmonary perfusion in small pulmonary arteries. Methods: Children with CHD, mainly those with transposition of the great arteries or tetralogy-of-Fallot, referred to CMR from 2020 to 2022 at our clinic, were retrospectively reviewed; n = 37. All patients had been examined with a free breathing, motion-corrected 4D flow protocol. Comparison in pulmonary perfusion (PPR: relative flow through right and left pulmonary arteries) with scintigraphy were performed both for 4D flow before and after partial volume correction. Results: Patients with large pulmonary arteries, 76%, displayed small differences in PPR between modalities (<20%), while patients with arteries of only a few pixels, 24%, displayed differences up to 178%, depending on the relative difference in size between the right and left pulmonary artery. Differences were effectively reduced after partial volume correction (<21%). Conclusion: The present report shows that 4D flow is a promising tool to accurately evaluate the pulmonary perfusion in children with CHD, but that partial volume correction is warranted to overcome its limitation in the spatial resolution. Without such correction, lung scintigraphy is still recommended to ensure high diagnostic certainty in children with small pulmonary arteries.

Childhood BMI trajectories predict cardiometabolic risk and perceived stress at age 13 years: the STARS cohort.

OBJECTIVE: The aim of this study was to examine BMI trajectories from birth throughout childhood, associations with health outcomes at age 13 years, and time frames during which early-life BMI influenced adolescent health. METHODS: Participants (1902, 44% male) reported perceived stress and psychosomatic symptoms and were examined for waist circumference (WC), systolic blood pressure (SBP), pulse wave velocity, and white blood cell counts (WBC). BMI trajectory was analyzed using group-based trajectory modeling of retrospective data of weight/height from birth throughout childhood. The authors performed linear regression to assess associations between BMI trajectories and health outcomes at age 13 years, presented as estimated mean differences with 95% CI among trajectories. RESULTS: Three BMI trajectories were identified: normal; moderate; and excessive gain. Adjusting for covariates, adolescents with excessive gain had higher WC (19.2 [95% CI: 18.4-20.0] cm), SBP (3.6 [95% CI: 2.4-4.4] mm Hg), WBC (0.7 [95% CI: 0.4-0.9] × 109 /L), and stress (1.1 [95% CI: 0.2-1.9]) than adolescents with normal gain. Higher WC (6.4 [95% CI: 5.8-6.9] cm), SBP (1.8 [95% CI: 1.0-2.5] mm Hg), and stress (0.7 [95% CI: 0.1-1.2]) were found in adolescents with moderate versus normal gain. The association of early-life BMI with SBP started around age 6 years with the excessive gain group, which was earlier than in the normal and moderate gain groups, in which it started at age 12 years. CONCLUSIONS: An excessive gain BMI trajectory from birth predicts cardiometabolic risk and stress in 13-year-old individuals.

Association between childhood BMI trajectories and cardiometabolic risk and mental health problems at the age of 13 years: the cohort STudy of Adolescence Resilience and Stress (STARS).

BACKGROUND: Research on BMI trajectories has been focused mainly on childhood and adolescence, missing birth and infancy, which are also relevant in the development of cardiometabolic disease in adulthood. We aimed to identify trajectories of BMI from birth throughout childhood, and to examine whether BMI trajectories predict health outcomes at the age of 13 years; and, if so, whether differences exist among trajectories regarding timeframes during which BMI in early life influences health outcomes. METHODS: Participants recruited from schools in the Västra Götaland region of Sweden completed questionnaires of perceived stress and psychosomatic symptoms and were examined for the following cardiometabolic risk factors: BMI, waist circumference, systolic blood pressure, pulse-wave velocity, and white blood cell counts. We collected ten retrospective measures of weight and height, from birth to the age of 12 years. Participants with at least five measures (at birth, one at age 6-18 months, two at age 2-8 years, and one at age 10-13 years) were included in the analyses. We used group-based trajectory modelling to identify BMI trajectories, ANOVA to compare different trajectories, and linear regression to assess associations. FINDINGS: We recruited 1902 participants (829 [44%] boys and 1073 [56%] girls, median age 13·6 years (IQR 13·3-13·8). We identified and named three BMI trajectories, and categorised participants accordingly: normal gain (847 [44%] participants), moderate gain (815 [43%] participants), and excessive gain (240 [13%] participants). Differences distinguishing these trajectories were established before the age of 2 years. After adjustments for sex, age, migrant background, and parental income, respondents with excessive gain had a higher waist circumference (mean difference 19·2 cm [95% CI 18·4-20·0]), higher systolic blood pressure (mean difference 3·6 mm Hg [95% CI 2·4-4·4]), more white blood cells (mean difference 0·7 × 109 cells per L [95% CI 0·4-0·9]), and higher stress scores (mean difference 1·1 [95% CI 0·2-1·9]), but similar pulse-wave velocity compared with adolescents with normal gain. Higher waist circumference (mean difference 6·4 cm [95% CI 5·8-6·9]), higher systolic blood pressure (mean difference 1·8 mm Hg [95% CI 1·0-2·5]), and a higher stress score (mean difference 0·7 [95% CI 0·1-1·2]) were also found in adolescents with moderate gain, compared with adolescents with normal gain. Regarding timeframes, we observed that a significant positive correlation of early life BMI with systolic blood pressure started approximately at the age 6 years for participants with excessive gain, much earlier than for participants with normal gain and moderate gain, for which it started at the age of 12 years. For waist circumference, white blood cell counts, stress, and psychosomatic symptoms, the timeframes were similar across the three BMI trajectories. INTERPRETATION: Excessive gain BMI trajectory from birth can predict both cardiometabolic risk and stress and psychosomatic symptoms in adolescents before the age of 13 years. FUNDING: Swedish Research Council (grant reference 2014-10086).

Longitudinal follow-up on vascular morphology and function in children with kidney transplants.

AIM: Our aim was to evaluate cardiovascular risk profile in 42 children with kidney transplants (KT) at the Queen Silvia Children's Hospital, Gothenburg Sweden. METHODS: Forty-two children (7.1-18 years) with KT, time from transplantation 3.5 (0.9-13) years, were examined at inclusion and annually for three consecutive years. Eighteen matched controls were examined once. Cardiovascular phenotyping included ultra-high-frequency ultrasound (UHFUS), pulse wave velocity (PWV), and endothelial function. RESULTS: Children with KT had higher body mass index (BMI) z-score and blood pressure (BP) z-score than healthy controls (BMI z-score: 0.4 ± 1.0 and - 0.2 ± 0.9, respectively, p = 0.02; SBP z-score: 0.5 ± 0.9 and - 0.8 ± 0.7; DBP z-score: 0.7 ± 0.7 and - 0.3 ± 0.5, respectively, p < 0.001). BP z-score decreased significantly over 3 years; other vascular markers remained unchanged. PWV and carotid intima thickness (IT) were higher in children with KT compared to healthy controls. Children with pre-emptive KT had lower radial IT and dorsal pedal media thickness (MT) compared to children with preceding dialysis. CONCLUSION: Children with KT show increased cardiovascular risk parameters, not increasing over time. Children on dialysis before KT have more pronounced vascular changes than those with pre-emptive KT, suggesting pre-emptive transplantation more beneficial for cardiovascular health.

Treatment decision in a 4-year-old-boy with left ventricular outpouching after advanced hemodynamical flow evaluation with 4Dflow CMR: A case report.

Background: The present study presents a diagnostic course for the characterization of a congenital left ventricular outpouching (LVO) in a 4-year-old boy with severe neonatal heart failure, evaluating the added value of cardiac magnetic resonance (CMR) 4Dflow. Case presentation: A boy, born at full term, presented with heart failure immediately after birth. Echocardiography showed dilated left ventricle with poor function and LVO was initially interpreted as an aneurysm. No infection, inflammation, or other cause for heart failure was found. With intensive medical treatment, the heart function returned to normal, and eventually, all medication was terminated. At follow-up, surgical treatment of the LVO was discussed but after CMR 4Dflow, a thorough evaluation of the function of the left ventricle as well as the LVO was possible and the LVO was determined a double-chambered left ventricle with a good prognosis. Conclusions: The present case demonstrates the clinical usability of CMR 4Dflow for improved decision-making and risk assessment, revealing advanced hemodynamic flow patterns with no need for operation.

Radial artery lumen diameter and intima thickness in patients with abdominal aortic aneurysm.

Objective: Abdominal aortic aneurysm (AAA) is associated with dilatation of central elastic arteries, while it is uncertain whether peripheral muscular arteries are affected. The aim of this study was to investigate radial artery diastolic lumen diameter (LD), wall thickness, and circumferential wall stress (CWS) in patients with AAA. Methods: We included 130 men with AAA (mean age, 70.4 ± 3.5 years) and 61 men without AAA (mean age, 70.5 ± 3.2 years) in the study. High-frequency ultrasound examination (50 MHz) was used to measure radial artery diameter, wall thickness, and CWS was calculated. Results: Men with AAA exhibited smaller radial artery LD (2.34 ± 0.42 mm vs 2.50 ± 0.38 mm; P < .01), thicker intima (0.094 ± 0.024 mm vs 0.081 ± 0.018 mm; P < .001), similar intima-media (0.28 ± 0.05 vs 0.26 ± 0.05 mm; P = NS), and lower CWS (42.9 ± 10.2 kPa vs 48.6 ± 11.4 kPa; P < .001), compared with controls. Subgroup analyses including all patients showed smaller LD and thicker intima in patients on statin therapy versus no statin therapy and current/ex-smoking versus never smoking. Individuals with hypertension versus no hypertension also presented with thicker intima, but with no difference in LD. Conclusions: AAAs demonstrated a smaller LD and thicker intima in the radial artery, in contrast with the theory of a general dilating diathesis of the arteries. Apart from AAA, other factors such as atherosclerosis, smoking habits, and hypertension might also be determinants of radial artery caliber and thickness. Clinical Relevance: The clinical relevance of this study is the added insight into the pathophysiology of abdominal aortic aneurysm (AAA). Today, the management of AAA is focused on reduction of general cardiovascular risk factors and treatment is based on surgical approaches when the AAA is already manifest. By shedding light on unknown pathophysiological aspects of AAA, it will eventually be possible to develop targeted pharmacological treatments to prevent the formation of AAA, to halt disease progression, and to find early cardiovascular markers of AAA.

Longitudinal Follow-Up on Cardiopulmonary Exercise Capacity Related to Cardio-Metabolic Risk Factors in Children With Renal Transplants.

Background: Children with chronic kidney disease, including those treated with kidney transplantation (KT), have an increased risk of cardiovascular disease. The aim of this study was to examine the cardiopulmonary exercise capacity after KT compared to matched controls, to relate the results to physical activity, blood pressure and biochemical findings and to follow exercise capacity over time. Methods: Patients with KT (n = 38, age 7.7-18 years), with a mean time from transplantation of 3.7 years (0.9-13.0) and mean time in dialysis 0.8 years, were examined at inclusion and annually for up to three years. Healthy controls (n = 17, age 7.3-18.6 years) were examined once. All subjects underwent a cardiopulmonary exercise test, resting blood pressure measurement, anthropometry and activity assessment. Patients also underwent echocardiography, dual-energy X-ray absorptiometry (DXA), 24-h ambulatory BP measurements (ABPM), assessment of glomerular filtration rate (GFR) and blood sampling annually. Results: As compared to healthy controls, KT patients showed decreased exercise capacity measured both as VO2peak (34.5 vs. 43.9 ml/kg/min, p < 0.001) and maximal load (2.6 vs. 3.5 W/kg, p < 0.0001), similarly as when results were converted to z-scores. No significant difference was found in weight, but the KT patients were shorter and had higher BMI z-score than controls, as well as increased resting SBP and DBP z-scores. The patient or parent reported physical activity was significantly lower in the KT group compared to controls (p < 0.001) In the combined group, the major determinants for exercise capacity z-scores were activity score and BMI z-score (ß = 0.79, p < 0.0001 and ß = -0.38, p = 0.007, respectively). Within the KT group, low exercise capacity was associated with high fat mass index (FMI), low activity score, low GFR and high blood lipids. In the multivariate analysis FMI and low GFR remained predictors of low exercise capacity. The longitudinal data for the KT patients showed no change in exercise capacity z-scores over time. Conclusion: Patients with KT showed decreased exercise capacity and increased BP as compared to healthy controls. Exercise capacity was associated to GFR, physical activity, FMI and blood lipids. It did not improve during follow-up.

Determinants of Intima-Media Thickness in the Young: The ALSPAC Study.

OBJECTIVES: This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years. BACKGROUND: Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. METHODS: Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences. RESULTS: Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: -0.0032; 95% CI: 0.004 to -0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor-associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor. CONCLUSIONS: Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.

The burden of alcohol on health care during COVID-19.

Alcohol's impact on global health is substantial and of a similar order of magnitude to that from COVID-19. Alcohol now also poses specific concerns, such as increased risk of severe lung infections, domestic violence, child abuse, depression and suicide. Its use is unlikely to aid physical distancing or other preventative behavioural measures. Globally, alcohol contributes to 20% of injury and 11.5% of non-injury emergency room presentations. We provide some broad comparisons between alcohol-attributable and COVID-19-related hospitalisations and deaths in North America using most recent data. For example, for Canada in 2017 it was recently estimated there were 105 065 alcohol-attributable hospitalisations which represent a substantially higher rate over time than the 10 521 COVID-19 hospitalisations reported during the first 5 months of the pandemic. Despite the current importance of protecting health-care services, most governments have deemed alcohol sales to be as essential as food, fuel and pharmaceuticals. In many countries, alcohol is now more readily available and affordable than ever before, a situation global alcohol producers benefit from and have helped engineer. We argue that to protect frontline health-care services and public health more generally, it is essential that modest, evidence-based restrictions on alcohol prices, availability and marketing are introduced. In particular, we recommend increases in excise taxation coupled with minimum unit pricing to both reduce impacts on health-care services and provide much-needed revenues for governments at this critical time.

Association between fat mass through adolescence and arterial stiffness: a population-based study from The Avon Longitudinal Study of Parents and Children.

BACKGROUND: The link between adiposity, metabolic abnormalities, and arterial disease progression in children and adolescents remains poorly defined. We aimed to assess whether persistent high adiposity levels are associated with increased arterial stiffness in adolescence and any mediation effects by common metabolic risk factors. METHODS: We included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had detailed adiposity measurements between the ages 9-17 years and arterial stiffness (carotid to femoral pulse wave velocity [PWV]) measured at age 17 years. Body-mass index (BMI) and waist-to-height ratio were calculated from weight, height, and waist circumference measurements whereas fat mass was assessed using repeated dual-energy x-ray absorptiometry (DEXA) scans. We used total and trunk fat mass indices (FMIs) to classify participants as normal (<75th percentile) or high (>75th percentile) FMI. We classified participants as being metabolically unhealthy if they had three or more of the following risk factors: high levels of systolic blood pressure, triglycerides, or glucose (all >75th percentile) or low levels of high-density lipoprotein (<25th percentile). We used multivariable linear regression analysis to assess the relationship between PWV and exposure to adiposity, and tested for linear trend of PVW levels across ordinal groups. We used latent class growth mixture modelling analysis to assess the effect of longitudinal changes in adiposity indices through adolescence on arterial stiffness. FINDINGS: We studied 3423 participants (1866 [54·5%] female and 1557 [45·5%] male). Total fat mass was positively associated with PWV at age 17 years (0·004 m/s per kg, 95% CI 0·001-0·006; p=0·0081). Persistently high total FMI and trunk FMI between ages 9 and 17 years were related to greater PWV (0·15 m/s per kg/m2, 0·05-0·24; p=0·0044 and 0·15 m/s per kg/m2, 0·06-0·25; p=0·0021) compared with lower FMI. Metabolic abnormalities amplified the adverse effect of high total FMI on arterial stiffness (PWV 6·0 m/s [95% CI 5·9-6·0] for metabolically healthy participants and 6·2 m/s [5·9-6·4] for metabolically unhealthy participants). Participants who restored normal total FMI in adolescence (PWV 5·8 m/s [5·7-5·9] for metabolically healthy and 5·9 m/s [5·6-6·1] for metabolically unhealthy) had comparable PWV to those who had normal FMI throughout (5·7 m/s [5·7-5·8] for metabolically healthy and 5·9 m/s [5·8-5·9] for metabolically unhealthy). INTERPRETATION: Persistently high fat mass during adolescence was associated with greater arterial stiffness and was further aggravated by an unfavourable metabolic profile. Reverting to normal FMI in adolescence was associated with normal PWV, suggesting adolescence as an important period for interventions to tackle obesity in the young to maximise long-term vascular health. FUNDING: UK Medical Research Council, Wellcome Trust, British Heart Foundation, and AFA Insurances.

Early vascular damage from smoking and alcohol in teenage years: the ALSPAC study.

Aims: To determine the impact of smoking and alcohol exposure during adolescence on arterial stiffness at 17 years. Methods and results: Smoking and alcohol use were assessed by questionnaires at 13, 15, and 17 years in 1266 participants (425 males and 841 females) from the ALSPAC study. Smoking status (smokers and non-smoker) and intensity ('high' ≥100, 'moderate' 20-99, and 'low or never' <20 cigarettes in lifetime) were ascertained. Participants were classified by frequency (low or high) and intensity of drinking [light (LI <2), medium (MI 3-9), and heavy (HI >10 drinks on a typical drinking day)]. Carotid to femoral pulse wave velocity (PWV) was assessed at 17 years [mean ± standard deviation and/or mean difference (95% confidence intervals)]. Current smokers had higher PWV compared with non-smokers (P = 0.003). Higher smoking exposure was associated with higher PWV compared with non-smokers [5.81 ± 0.725 vs. 5.71 ± 0.677 m/s, mean adjusted difference 0.211 (0.087-0.334) m/s, P = 0.001]. Participants who stopped smoking had similar PWV to never smokers (P = 0.160). High-intensity drinkers had increased PWV [HI 5.85 ± 0.8 vs. LI 5.67 ± 0.604 m/s, mean adjusted difference 0.266 (0.055-0.476) m/s, P = 0.013]. There was an additive effect of smoking intensity and alcohol intensity, so that 'high' smokers who were also HI drinkers had higher PWV compared with never-smokers and LI drinkers [mean adjusted increase 0.603 (0.229-0.978) m/s, P = 0.002]. Conclusion: Smoking exposure even at low levels and intensity of alcohol use were associated individually and together with increased arterial stiffness. Public health strategies need to prevent adoption of these habits in adolescence to preserve or restore arterial health.

Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are exposed to both traditional 'Framingham' and uremia related cardiovascular risk factors that drive atherosclerotic and arteriosclerotic disease, but these cannot be differentiated using conventional ultrasound. We used ultra-high-frequency ultrasound (UHFUS) to differentiate medial thickness (MT) from intimal thickness (IT) in CKD patients, identify their determinants and monitor their progression. METHODS: Fifty-four children and adolescents with CKD and 12 healthy controls underwent UHFUS measurements using 55-70MHz transducers in common carotid and dorsal pedal arteries. Annual follow-up imaging was performed in 31 patients. RESULTS: CKD patients had higher carotid MT and dorsal pedal IT and MT compared to controls. The carotid MT in CKD correlated with serum phosphate (p<0.001, r = 0.42), PTH (p = 0.03, r = 0.36) and mean arterial pressure (p = 0.03, r = 0.34). Following multivariable analysis, being on dialysis, serum phosphate levels and mean arterial pressure remained the only independent predictors of carotid MT (R2 64%). Transplanted children had lower carotid and dorsal pedal MT compared to CKD and dialysis patients (p = 0.02 and p = 0.01 respectively). At 1-year follow-up, transplanted children had a decrease in carotid MT (p = 0.01), but an increase in dorsal pedal IT (p = 0.04) that independently correlated with annualized change in BMI. CONCLUSIONS: Using UHFUS, we have shown that CKD is associated with exclusively medial arterial changes that attenuate when the uremic milieu is ameliorated after transplantation. In contrast, after transplantation intimal disease develops as hypertension and obesity become prevalent, representing rapid vascular remodeling in response to a changing cardiovascular risk factor profile.

Impact of psychological health on peripheral endothelial function and the HPA-axis activity in healthy adolescents.

BACKGROUND AND AIMS: The development of adolescence psychological health over a 3-year period and its relationship to peripheral endothelial function and the hypothalamic-pituitary-adrenal (HPA)-axis activity were examined in a cohort of healthy adolescents in a longitudinal study. METHODS: A total of 162 adolescents (94 females) participated in both baseline (mean age 14.5 ± 1 years) and three-year follow-up studies. Psychological health was evaluated by self-report using the Beck Youth Inventories of Emotional and Social Impairment and the psychosomatic problem scale. Peripheral endothelial function was assessed using a peripheral artery tonometry device. The HPA-axis activity measured as cortisol awakening response (CAR) was assessed only at follow-up by collecting two saliva samples, immediately after awakening and 15 min later. Physical activity, smoking and parental education were assessed by questionnaires. RESULTS: Adolescents reported increased depression and decreased anger over three years, while only females reported increased psychosomatic complaints. Reduced peripheral endothelial function was associated with high level of anger (ß = -0.332, p = 0.018) and disruptive behaviour (ß = -0.390, p = 0.006) over three years in males, but not in females, after adjusting for covariates. Blunted cortisol awakening response was associated with high level of anxiety (ß = -0.235, p = 0.017), depression (ß = -0.203, p = 0.038), anger (ß = -0.185, p = 0.048), and low level of self-concept (ß = 0.289, p = 0.002) after adjusting for covariates. CONCLUSIONS: High level of negative emotions during adolescence may have adverse effects on peripheral endothelial function and the regulation of the HPA-axis activity, while high level of self-concept might be protective.

Selection biases in observational studies affect associations between 'moderate' alcohol consumption and mortality.

Selection biases may lead to systematic overestimate of protective effects from 'moderate' alcohol consumption. Overall, most sources of selection bias favor low-volume drinkers in relation to non-drinkers. Studies that attempt to address these types of bias generally find attenuated or non-significant relationships between low-volume alcohol consumption and cardiovascular disease, which is the major source of possible protective effects on mortality from low-volume consumption. Furthermore, observed mortality effects among established low-volume consumers are of limited relevance to health-related decisions about whether to initiate consumption or to continue drinking purposefully into old age. Short of randomized trials with mortality end-points, there are a number of approaches that can minimize selection bias involving low-volume alcohol consumption.

[Moderate alcohol consumption brings no positive effect on health. A critical research analysis]. / Måttlig alkohol-konsumtion ger ingen positiv hälsoeffekt - En kritisk forskningsanalys.

The evidence for the beneficial health effects of moderate drinking is weaker than commonly perceived. No randomised controlled trials have been done. Observational studies suffer from unavoidable methodological limitations, chiefly from confounding and misclassification. Clinical advice to patients as well as public health recommendations should discourage initiation of alcohol consumption, as well as recommend the reduction of excessive drinking. The absence of health benefits strengthens the the arguments for effective population-level policies, e.g. raising alcohol prices and restricting the physical availability of alcohol.

Has the leaning tower of presumed health benefits from 'moderate' alcohol use finally collapsed?

The evolving epidemiological literature, including improved methodology for assessing causality in observational studies, is raising doubts about whether moderate alcohol consumption has a protective effect on health.