Connor Iapoce is an assistant editor for 

 and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at 

Connor Iapoce

, most studies on associations between high low-density lipoprotein cholesterol (LDL-C) levels and CVD are only measured at one time point in life, leaving a lack of data on long-term exposure to LDL-C.

In a recent cohort study, investigators, led by Yiyi Zhang, PhD, Division of General Medicine, Columbia University Medical Center, looked to evaluate the association of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age, with incident CVD in later life.

Results from the study showed cumulative LDL-C and TWA LDL-C during these time periods were associated with the risk of incident CVD, regardless of LDL-C level at midlife.

The study conducted an analysis of 4 large, community-based prospective cohort studies in the United states, including the Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis.

For inclusion criteria, participants were included with ≥2 LDL-C measures that were at least 2 years apart between ages 18 - 60 years, with 1 of the LDL-measures taking place in middle age (40 - 60 years).

The team defined the index visit as the last visit during the middle-age period with an observed LDL-C measurement.

Further, the defined primary exposures of interest as cumulative exposure to LDL-C, TWA LDL-C, and LDL-C scope from ages 18 - 60 years. Then, primary outcomes of interest for the present analysis were incident Exposure to LDL-C in Young Adults Linked to Risk of Incident Coronary Heart Disease (CHD), ischemic stroke, and heart failure (HF).

Additionally, investigators used cox proportional hazards regression models to examine associations between LDL-C exposure and incident CVD events.

Out of the 4 cohort studies, a total of 18,288 participants were included. They had a mean age of 56.4 years at index visit, including 10,309 women (56.4%) and 7979 men (43.6%). 

Through a median follow-up of 16 years, investigators observed a total of 1165 incident CHD, 599 ischemic stroke, and 1145 HF events. 

Further, the team used the multivariable Cox proportional hazards regression model that adjusted for most recent LDL-C levels measured during middle age and other CVD risk factors.

As a result, the hazard ratios for CHD included 1.57 (95% CI, 1.10 - 2.23, 

 = .01), for cumulative LDL-C level, 1.69 (95% CI, 1.23 - 2.31, 

 <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69 - 1.12, 

Investigators noted a lack of association between any LDL-C variables and ischemic stroke or heart failure.

They found that associations were similar in women (HR 1.82; 95% CI, 1.07 - 3.10) and in men (HR 1.67; 95% CI, 1.06 - 2.64).

In participants who never used lipid-lowering medication (n = 15,626), data show TWA LDL-C level remained significantly associated with incident CHD (HR 1.54; 95% CI, 1.08 - 2.18).

As a result, greater exposure to LDL-C and TWA-C at young adulthood and middle age were associated with an increased risk of CHD, which remained after adjustment for the most recent LDL-C level during middle age.

“These findings suggest that previous levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels throughout young adulthood and middle age may reduce the lifetime risk of developing atherosclerotic CVD,” investigators wrote.

Association Between Cumulative Low-Density Lipoprotein Cholesterol Exposure During Young Adulthood and Middle Age and Risk of Cardiovascular Events

Articles

Hazard ratios for CHD included 1.57 for cumulative LDL-C level, 1.69 for TWA LDL-C level, and 0.88 for LDL-C slope. 

Exposure to LDL-C in Young Adults Linked to Risk of Incident Coronary Heart Disease

4:05 - What is the multidisciplinary approach?

If the crisis point is the moment where a crisis will worsen or begins to get better, the question remains: Where are we now?

, a comprehensive look at the public health crises affecting the United States today, with global implications tomorrow. 

 of the series took on the scope of the obesity crisis and the larger framework of the disease space.

This episode goes beyond that - to the actual structure of care that clinicians in this medical space deal with on a daily basis.

We discuss the multidisciplinary approach, bariatric surgical options, and body mass index (BMI), with a lens focusing on the clinical burdens that these clinicians face in the pursuit of care.

Once again, we are joined by the experts and advocates in the obesity care space who share their expertise and knowledge on the subject.

Hans Schmidt, MD, Division Chief, Bariatric Surgery, Hackensack University Medical Center

Jun Tashiro, MD, Pediatric Surgeon, Hassenfeld Children’s Hospital, NYU Langone Health

Jose Aleman, MD, Assistant Professor, NYU Langone Health

Louis Aronne, MD, Chief Medical Officer of Intellihealth and Medical Director, Comprehensive Weight Control Center, Weill Cornell Medical Center.

Next week’s episode will tackle the regional differences found in obesity care, from location and demographics to food options and nutritional ability.

Thanks for watching and stay tuned for more from 

Videos

Episode 2 of HCPLive Crisis Point tackles the clinical aspects and potential burdens clinicians face in the pursuit of obesity care. 

Burdens of Clinical Care in the Obesity Crisis 

 has shifted toward vascular endothelial growth factor (VEGF) inhibitors, there is limited data showing significantly improved vision in routine clinical care.

A team of investigators, led by Adrian Hunt, MBBS, The Save Sight Institute, Sydney Medical School, University of Sydney, aimed to compare 12-month treatment outcomes of aflibercept or ranibizumab for macular edema secondary to central retinal vein occlusion (CRVO) in routine clinical care.

The team observed both agents, aflibercept and ranibizumab, improved visual acuity (VA) and reduced central subfield thickness (CST) in eyes with CRVO in routine clinical practice.

Investigators performed a retrospective analysis of eyes with CRVO treated with intravitreal anti-VEGF agents. The patients were considered treatment-naive and managed at clinics in Australia, France, Switzerland, and the United Kingdom.

At each clinical visit, data was collected including the number of letters read on a logarithm of the minimum angle of resolution (logMAR) VA Chart, the active of cystoid macular edema, CST measured using spectral-domain optical coherence tomography (OCT), and treatment given.

Additionally, information on treatment-naive eyes that started treatment with ranibizumab or aflibercept for macular edema secondary to CRVO were recruited from centers using the prospectively designed Fight Retinal Blindness (FRB) Registry.

The primary outcome was the mean change in VA at 12 months between anti-VEGF agents, while secondary outcomes included mean changes in CST, injections and visits, time to first grading of inactivity, switching and non-completion from baseline to 12 months.

In identification of participants, investigators found 296 treatment-naive patient eyes (125 ranibizumab and 171 aflibercept) in 291 patients with cystoid macular edema secondary to CRVO. Patients started treatment from June 2014 - June 2019.

Additionally, investigators noted baseline VA had slight improvement in aflibercept versus ranibizumab treated eyes (42.5 ± 25.5 letters versus 36.9 ± 26 letters; 

Data show the mean crude VA improvement was higher for aflibercept versus ranibizumab (+13.1 letters versus +9.9, 

Moreover, data also show the 12-month adjusted mean VA change was +16.6 (95% CI, 12.9 - 20.4) letters for aflibercept in comparison to +9.8 (95% CI, 5.5 - 14.1) letters for ranibizumab, all 

Further, investigators found a similar CST (614 μm versus 616 μm, P = .95), but at 12 months, the mean CST was significantly lower in the aflibercept group compared to the ranibizumab group (313 μm versus 370 μm).

In eyes presenting with poor VA, the mean adjusted change in CST had significantly greater changes in aflibercept versus ranibizumab-treated eyes (304 μm versus 252 μm, 

In addition, both groups had a median of 7 injections and 10 visits. Investigators noted aflibercept-treated eyes received some more injections, but was not considered statistically significant.

Further, the cox-proportional hazards model predicted aflibercept (9 eyes, 5%) became inactive at a quicker pace than ranibizumab (26 eyes, 21%), all 

Ultimately, investigators noted that eyes receiving aflibercept had larger visual gains and reductions in CST.

“The combination of stronger and potentially longer VEGF suppression of aflibercept may be one of the main drivers for better clinical outcomes since the more prolonged suppression may compensate for the somewhat lower number of injections,” investigators wrote.

12-month outcomes of ranibizumab versus aflibercept for macular oedema in central retinal vein occlusion: data from the FRB Registry

Baseline VA show slight improvement in aflibercept versus ranibizumab treated eyes, (42.5 letters versus 36.9 letters). 

Aflibercept, Ranbizumab Shown To Improve Visual Acuity in Eyes with CRVO 

Although an association between the risk of tuberculosis (TB) and 

 status has been considered likely from previous epidemiological studies, there is not well established data on the consideration of impaired fasting glucose or duration of diabetes.

In a recent study, Dong Wook Shin, MD, Supportive Care Center, Sungkyunkwan University School of Medicine and colleagues investigated the risk of TB incidence according to diabetes status in a nationwide database.

They found a longer diabetes duration had a greater association with the development of TB, while patients with new-onset diabetes had a higher level of incident TB with a fasting plasma glucose (FPG) level of ≥202 mg/dL.

Investigators performed a population-based cohort study using data from the Korean National Health Insurance System database, which covers 97% of the Korean population.

The study included adult participants (n = 5,292,827) who underwent a health screening in 2009, without a history of TB. Patient exclusions included diagnosis of anemia, cancer, end-stage kidney disease, as well as patients with a history of TB or a new TB diagnosis.

In determining diabetes status at baseline, patients were classified according to glycemic status. The 5 categories included normal glucose (FPG <100 mg/dL, IFG (FPG 100 - 125 mg/dL), new-onset diabetes (FPG ≥126 mg/dL without diabetes diagnosis), diabetes duration <5 years, and diabetes duration ≥5 years.

Moreover, study participants were followed from baseline to date of TB diagnosis, censoring, or the end of the study period in December 2018. The primary outcome was considered a new TB diagnosis.

In patients with new-onset diabetes, the FPG level was categorized by decile, with decile 1 (lowest) showing <128 mg/DL and decile 10 (highest) showing ≥202 mg/dL.

Investigators used cox proportional hazards models to evaluate the association of diabetes status with TB incidence. Data analysis took place from September 2019 - September 2020.

A total of 4,423,177 participants were included in the final study population, with a mean age of 46.5 years and 58.7% men (n = 2,597,142).

Data show the distribution of the study cohort included normal glucose (n = 3,030,004; 68.5%; IFG (n = 1,017,410; 23.0%); new-onset diabetes (n = 135,448, 3.1%); diabetes duration <5 years (n = 128 882, 2.9%); and diabetes duration ≥5 years (n = 111,433; 2.5%).

The team observed a total of 26,458 new cases of TB, consisting of 0.6% of the total population, over the median follow-up duration of 8.3 years.

Further, they saw the risk of TB was 48% higher in patients with diabetes compared to those without diabetes (adjusted hazard ratio aHR, 1.48; 95% CI. 1.42 - 1.53)

Additionally, participants with IFG showed no increased risk of TB incidence (aHR, 0.97; 95% CI, 0.93 - 1.01).

However, the risk of TB incidence was shown to increase with diabetes duration, consisting of new-onset diabetes (aHR, 1.32; 95% CI, 1.23 - 1.42), diabetes duration <5 years (aHR, 1.45; 95% CI, 1.36 - 1.54), diabetes duration ≥5 years (aHR, 1.57; 95% CI, 1.48 - 1.66).

A higher incidence of TB in patients with diabetes duration ≥5 years had strong associations in men (aHR, 1.84; 95% CI, 1.72 - 1.98) and younger participants aged <45 years (aHR, 4.61; 95% CI, 3.62 - 5.88).

Investigators concluded their results showed participants with diabetes had a 48% higher risk of TB incidence, while participants without diabetes and IFG had no increased risk for TB.

Additionally, they noted the association between diabetes and TB was stronger in patients with a longer diabetes duration.

“However, the effect of diabetes duration on TB risk has not been well established, and our study provides important implications that not only uncontrolled diabetes status but also diabetes duration can affect TB occurrence,” investigators wrote.

Diabetes Status and Association With Risk of Tuberculosis Among Korean Adults

The risk of TB was 48% higher in patients with diabetes compared to those without diabetes, while participants with IFG showed no increased risk of TB incidence. 
