Minding the Gaps: Projecting the Consequences of Altering ASCVD Risk Thresholds on Type 2 Diabetes and ASCVD

While the cardioprotective effect of statins are undeniable, experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk. However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we aimed to project the benefits and harms of statin treatment in primary prevention adult populations newly eligible for statin treatment using four proposed statin treatment recommendations. First, we conducted a meta-analysis of statin-associated T2D risk among randomized controlled trials (RCTSs) and observational studies (OBSs), excluding studies conducted among secondary prevention populations. We identified 23 studies (35% RCTs) of n=4,012,555 participants. There was little evidence for publication bias (P>0.1); however, evidence of heterogeneity was observed overall and among OBSs and RCTs (PCochran=<0.05). Findings from the meta-analysis provided us with statin-associated T2D risks to be used to project the benefits and harms of statin treatment. A series of simulations were constructed using Markov models and contemporary data from biracial (African American and Caucasian), adult (aged 40-75) national population-based surveys and published meta-analyses. Statin treatment eligibility for each of four recommendations was determined by 10-year atherosclerosis cardiovascular disease (ASCVD) risk and, for one recommendation, age. This simulation framework was used to project statin-associated absolute benefit, quantified as the number needed to treat (NNT) to prevent one ASCVD event, absolute harm, quantified as number needed to harm (NNH) to incur one incident T2D, and relative benefit, quantified as the likelihood to be helped or harmed (LHH, NNH/NNT). Overall, the number of ASCVD events prevented was at least twice as large as the number of incident T2D incurred (LHH range: 2.10-2.90). However, the relative benefit of statin treatment decreased when higher statin-associated T2D RRs were assumed. Findings highlight the higher relative burden of T2D occurred among female and younger adult populations, with disparities widening as statin-associated T2D RR increased, underscoring the need for more research quantifying statin-associated benefits and harms.Doctor of Public Healt

Disparities in Early Transitions to Obesity in Contemporary Multi-Ethnic U.S. Populations

Few studies have examined weight transitions in contemporary multi-ethnic populations spanning early childhood through adulthood despite the ability of such research to inform obesity prevention, control, and disparities reduction

Projections of incident atherosclerotic cardiovascular disease and incident type 2 diabetes across evolving statin treatment guidelines and recommendations: A modelling study

BACKGROUND: Experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation. METHODS AND FINDINGS: Simulations were conducted using Markov models that integrated data from contemporary population-based studies of non-Hispanic African American and white adults aged 40–75 years with published meta-analyses. Statin treatment eligibility was determined by predicted 10-year ASCVD risk (5%, 7.5%, or 10%). We calculated the number needed to treat (NNT) to prevent one ASCVD event and the number needed to harm (NNH) to incur one incident case of T2D. The likelihood to be helped or harmed (LHH) was calculated as ratio of NNH to NNT. Heterogeneity in statin-associated benefit was examined by sex, age, and statin-associated T2D relative risk (RR) (range: 1.11–1.55). A total of 61,125,042 U.S. adults (58.5% female; 89.4% white; mean age = 54.7 years) composed our primary prevention population, among whom 13–28 million adults were eligible for statin initiation. Overall, the number of ASCVD events prevented was at least twice as large as the number of incident cases of T2D incurred (LHH range: 2.26–2.90). However, the number of T2D cases incurred surpassed the number of ASCVD events prevented when higher statin-associated T2D RRs were assumed (LHH range: 0.72–0.94). In addition, females (LHH range: 1.74–2.40) and adults aged 40–50 years (LHH range: 1.00–1.14) received lower absolute benefits of statin treatment compared with males (LHH range: 2.55–3.00) and adults aged 70–75 years (LHH range: 3.95–3.96). Projected differences in LHH by age and sex became more pronounced as statin-associated T2D RR increased, with a majority of scenarios projecting LHHs &lt; 1 for females and adults aged 40–50 years. This study’s primary limitation was uncertainty in estimates of statin-associated T2D risk, highlighting areas in which additional clinical and public health research is needed. CONCLUSIONS: Our projections suggest that females and younger adult populations shoulder the highest relative burden of statin-associated T2D risk

Author Correction: Transitions from Ideal to Intermediate Cholesterol Levels may vary by Cholesterol Metric

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the pape

Smoothed age (2–80 years)-, race/ethnic-, and sex-specific prevalence proportions of normal weight (solid line), overweight (dashed line), and obesity (dotted line) estimated in n = 21,220 NHANES participants.

<p>Smoothed age (2–80 years)-, race/ethnic-, and sex-specific prevalence proportions of normal weight (solid line), overweight (dashed line), and obesity (dotted line) estimated in n = 21,220 NHANES participants.</p

One-year age-specific population extrapolations of the net number of non-institutionalized African American, Caucasian, and Mexican American males and females 2–80 years of age transitioning to overweight and obesity.

<p>One-year age-specific population extrapolations of the net number of non-institutionalized African American, Caucasian, and Mexican American males and females 2–80 years of age transitioning to overweight and obesity.</p

Age (2–80 years)-, race/ethnic-, and sex-specific overweight-to-obesity net transition probabilities estimated in n = 21,220 NHANES participants.

<p>Age (2–80 years)-, race/ethnic-, and sex-specific overweight-to-obesity net transition probabilities estimated in n = 21,220 NHANES participants.</p

Race/ethnic- and sex-specific demographics for n = 21,220 NHANES (2007–12) participants 2–80 years of age used to characterize the age-specific net probability of transitioning between normal weight, overweight, and obesity.

<p>BMI, body mass index; N, unweighted number; IQR, interquartile range.</p

Age (2–80 years) race/ethnic-, and sex-specific normal weight–to- overweight net transition probabilities estimated in n = 21,220 NHANES participants.

<p>Age (2–80 years) race/ethnic-, and sex-specific normal weight–to- overweight net transition probabilities estimated in n = 21,220 NHANES participants.</p