2 Minute Medicine Rewind Jan 25, 2021

Independent and Synergistic Effects of High Blood Pressure and Obesity on Retinal Vasculature in Young Children: The Hong Kong Children Eye Study

1. Hypertension and overweight to obese BMI in children were associated with changes in retinal microvasculature.

Evidence Rating Level: 2 (Good)

Hypertension and obesity, two of the most important risk for cardiovascular diseases, are growing increasingly prevalent in childhood due to a shift in health behaviours towards a sedentary lifestyle, poor dietary patterns, and increased screen time. Less is known about the impact of blood pressure and/or weight, specifically fat distribution, on retinal microvasculature at a younger age. In this ongoing population-based cohort study, as a subset of the Hong Kong Children Eye Study, 1006 children aged 6 to 8 years underwent full ophthalmic and physical examinations as well as standardized interviews. Retinal photographs visualized retinal vessel calibers, and sitting blood pressure, BMI, and weight-to-height ratio (WHtR) were measured. Compared to overweight and normal weight children, obese children had the smallest arteriolar fractal dimensions (1.211 vs 1.234 and 1.240, p-trend=0.004). Hypertensive systolic blood pressure was significantly associated with the narrowest central retinal arteriolar equivalents (CRAE) over elevated or normotensive systolic blood pressure (162.4 vs 164.6 and 167.1um, p-trend <0.001). Moreover, children with hypertension who were either overweight or obese had the narrowest CRAE(p-trend <0.001) and smallest arteriolar Df value, or the simplest vascular network (p-trend=0.007). While weight-to-height ratio was not associated with retinal vascular parameters, both overweight to obese BMI and hypertensive blood pressure were independent and synergestic factors in changing retinal microvasculature in children. Although longitudinal studies would be necessary to study how these microvasculature changes may predict cardiovascular events, these results support the implementation of initiatives to lower childhood cardiovascular risk in schools and communities.


Liver Fibrosis Scoring Systems as Novel Tools for Predicting Cardiovascular Outcomes in Patients Following Elective Percutaneous Coronary Intervention

1. Post-PCI patients with intermediate to high liver fibrosis scores were observed to experience higher incidences of major cardiovascular events.

Evidence Rating Level: 1 (Excellent)

While the introduction of percutaneous coronary interventions (PCI) have significantly reduced the rate of major cardiovascular events in patients with coronary artery disease, patients post-PCI continue to have a high risk for recurrent events and cardiovascular-related mortality. There is growing evidence that in both patients with non-alcoholic fatty liver disease (NAFLD) and the general population, the degree of liver fibrosis is a strong predictor for cardiovascular risk, of disease, events, as well as related and all-cause mortality. Although the gold standard for diagnosis of liver fibrosis is a liver biopsy, this study investigated whether noninvasive scoring systems may be a safe and accessible screening tool to predict long-term cardiovascular outcomes, particularly in patients without symptoms of or history of liver disease. In this multicentre, prospective study, 4003 patients (mean age 56.8+ 10.5 years, 76.5% male) with stable coronary artery disease undergoing PCI were assessed by eight current liver fibrosis scores (LFS) at baseline, before being followed for an average of 5.0 + 1.6 years. At 6month intervals, patients would be interviewed to assess for incidence of the primary endpoint, a composite of cardiovascular-related death, non-fatal myocardial infarction, and ischemic stroke, as well as the secondary endpoint, which included the composite primary endpoint in addition to unplanned revascularization and hospitalized unstable angina. Patients with confirmed diagnosis of liver disease and/or excessive alcohol consumption were excluded. 315 major cardiovascular events and 83 cardiovascular-related deaths were reported. Those who developed these cardiac events were more likely to have intermediate or high LFSs, based on NAFLD fibrosis score, fibrosis-4 score, BMI, AST/ALT ratio, and diabetes melitus score (BARD). Patients with intermediate to high score levels were at a significantly elevated risk, by 1.57-1.92 fold, of experiencing cardiovascular events included in the primary endpoint over patients with low LFSs. 1-SD increment on the NAFLD fibrosis score, fibrosis-4 score, AST/ALT ratio, or the BARD was associated with a 7%-59% increased risk of experiencing cardiovascular events, even after adjusting for sex, age, cardiovascular-related comorbidities, and diabetes. Adding NAFLD fibrosis score, fibrosis-4 score, and BARD to a model of established cardiovascular risk factors improved its predictability of the primary endpoint; only the NAFLD fibrosis score was independently associated with the risk of secondary endpoint events. Continued follow-up on liver fibrosis scores after baseline and conducting liver biopsies to find any unrecognized liver diseases may strengthen the results. Nonetheless, these findings support liver fibrosis scores as non-invasive, novel tools to identify high-risk patients post-PCI and aid clinical decision-making in cardiovascular risk prevention.


Alcohol consumption and risk of cardiovascular outcomes and bleeding in patients with established atrial fibrillation

1. Low to moderate alcohol intake was not significantly associated with risk of stroke or other cardiovascular outcomes in patients with atrial fibrillation.

Evidence Rating Level: 2 (Good)

“Holiday heart syndrome” describes the association found between excessive alcohol intake and incidence of atrial arrhythmias. Even low amounts of regular alcohol intake have been associated with an increased risk of incident atrial fibrillation (AF). With alcohol consumption associated with an increased stroke risk in patients without AF and likely to increase bleed risk, many physicians recommend patients with AF, who are already at an elevated stroke risk and taking anticoagulants, to abstain from alcohol. However, the effects of alcohol intake on the risk of adverse events in patients with AF has been poorly studied. Results from two comparable prospective cohort studies conducted in Switzerland, BEAT-AF and Swiss-AF,  were combined, following a total of 3 852 patients with AF (mean age 71 + 10 years, 28% women, 85% on anticoagulants) for a median of 3.0 years.Data was collected from yearly follow-up visits and hospital records, and standardized case report forms were used to collect baseline personal characteristics. Analyses were conducted using time-updated multivariable-adjusted Cox proportional hazards models, which included adjustments first for age and sex, then for social factors, comorbidities, health behaviours, type of AF, as well as health perception. For the primary outcome, a composite endpoint of stroke and systemic embolism incidence, 136 strokes and systemic embolisms were reported. Patients were categorized into cohorts of nondrinkers, those who consumed >0 to <1 drinks/day, 1-<2 drinks/day, and >2 drinks/day. Drinking from any cohort was not significantly associated with a higher incidence of the primary outcome compared to nondrinkers (aHR: 0.87 (95% CI 0.55-1.37), 0.70 (95% CI 0.39-1.25), 0.96 (95% CI 0.56-1.6) respectively). Neither was any association found between alcohol consumption and incidence of bleeding. However, there was a nonlinear association between alcohol consumption and hospital admission for heart failure (p for quadratic trend=0.01) and myocardial infarction (p for quadratic trend=0.007). Those drinking 1 to <2 drinks/day were also nonlinearly associated with having the lowest risk of death (p for quadratic trend=0.001). Limitations of this study include its observational nature, the sample population was mostly white, that drinking was measured by self-reporting and may have been underreported, and the lack of heavy or binge drinkers in the study population, to which these results may not be as applicable. Overall, as there was no significant association found between low to moderate alcohol intake with stroke risk, other cardiovascular events, or increased bleed risk, these findings do not support any special recommendations for AF patients regarding alcohol consumption.


Association between county level cannabis dispensary counts and opioid related mortality rates in the United States: panel data study

1. Increasing medical and recreational dispensary counts were associated with reduced opioid-related mortality rates per county in the United States.

Evidence Rating Level: 2 (Good)

With opioid-related mortality rising sharply since 1999 and accounting for over two thirds of all US drug overdose deaths in 2018, research into how changes in the overall supply of other drug markets may affect this public health crisis. Some studies have found a negative association between opioid-related mortality rates and the legalization of medical and/or recreational cannabis, while other studies have found this association non-significant. This study examines whether legally authorizing storefront dispensaries to sell cannabis, medical and/or recreational, would impact opioid mortality rates per county. Using panel regression methods, US mortality data from Centres for Disease Control and Prevention, US census data, and data from Weedmaps.com on storefront dispensary operations were analyzed by county from 2014-2018, a period of considerable change in cannabis legalization in the country. Models included controls for whether a state allowed for recreational sales and what kinds of opioid interventions (ie naloxone access) were available. As opioid-related mortality rates have recently been largely driven by deaths from synthetic opioids like fentanyl, opioid-related deaths were also categorized by prescription opioids, heroin, and synthetic opioids other than methadone. While eight states and the District of Columbia have authorized selling recreational cannabis, fifteen states legalized selling only medical forms. Dispensary count by county (natural log) was negatively associated with the log-transformed, age-adjusted mortality rate from all opioid types (β=-0.17, 95% CI: -0.23 to -0.11). This association remained significant with numbers of medical and recreational dispensaries separately: an increase from one to two medical and recreational dispensaries corresponded to an estimated 15% and an estimated 11% reduction in deaths respectively. Overall, an increase from one to two dispensaries per county correlated with an estimated 17% reduction in opioid-related mortality rate. Increases in dispensary count were also significantly and negatively associated with synthetic, non-methadone opioids, with an increase from one to two medical dispensaries reducing mortality rates by 14% (β=−0.14, 95% CI: −0.21 to −0.07) and a similar increase in recreational dispensaries resulting in a 21% reduction (β=−0.21, 95% CI: −0.29 to −0.13). However, only medical dispensary count, not recreational, was negatively associated with heroin-related and prescription-related mortality rates. While no causal relationship can be established from this observed negative association between cannabis dispensary counts and opioid-related mortality rates, these findings support further investigation into how the accessibility and structure of other drug markets may impact opioid use and misuse.


Time restricted eating as a weight loss intervention in adults with obesity

1. Practicing time-restricted eating achieved modest weight loss in adults with obesity after 12 weeks.

Evidence Rating Level: 2 (Good)

Resistant hypertension, which is uncontrolled despite maximal medical therapy, affects up to 10% of patients diagnosed with hypertension. Renal artery denervation has been demonstrated in a number of smaller, nonrandomized and/or unblinded studies to significantly reduce blood pressure in patients with resistant hypertension. About 10% of morbidity and mortality in the UK results from ill health due to obesity. Intermittent fasting has shown promising results in both animals and humans for weight loss, as well as improvements in glucose metabolism and lipid profiles in people. However, this approach, which alternates total or partial energy restriction with non-restricted energy, is restrictive and demanding, and therefore not used in clinical practice. Time-restricted eating (TRE), or the 16:8 diet, is a less severe format which limits dieters to consume only within an 8-hour window every day. Small samples and varying results and trial protocols in previous studies give little information on the true effects of TRE on weight and lipid profile. In this pilot cohort study, 50 participants with obesity (mean age 50 years old, mean BMI = 35, 74% female) were asked to only eat during an 8-hour window every day, while water, diet drinks, or coffee or tea without sugar or milk were permitted for the remaining 16 hours. Participants completed questionnaires and had their weight taken at baseline, 6 weeks, and 12 weeks, in addition to their blood pressure and lipid profile measured at the beginning and end of the study. Weekly phone calls monitored their adherence from weeks 2-5. With the primary outcome as adherence, 80% and 78% provided data at 6 and 12 weeks, with 58% of participants continuing to adhere to TRE on at least 5 days/week by week 12. Those who provided follow-up data and adhered to the TRE intervention for at least 5 days/week recorded greater weight loss at 6 and 12 weeks, with 2.5+ 1.7 kg vs 1.0 + 1.3kg (p=0.003) at 6 weeks and 3.5+ 2.7 kg vs 1.3+ 2.0 kg, p=0.001 at 123 weeks. Overall, 26% of participants lost at least 5% of their body weight by 12 weeks. No effect on blood pressure or lipid profile was observed. The most common barriers to adherence reported were related to social activity, such as dining out, having visitors, and having drinks after work, while participants reported planning ahead, using distraction, and/or drinking water or black coffee to cope with hunger. While the magnitude of weight loss from TRE intervention was modest, previous studies using more complex regimens produced similar results. Overall, these findings are encouraging and conducting a randomized controlled trial using a similar TRE protocol with a longer follow-up could further support these results.

Image: PD

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