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Risk of CVD or type-2 diabetes according to change in BMI after starting ART

Gareth Hardy, HIV i-Base

Initiation of ART usually leads to increased weight and body mass index [BMI] that might be associated with an increased risk of cardiovascular disease [CVD] and type II diabetes.

Amit Achhra at the Kirby Institute for Infection and Immunity in Society, in Sydney, investigated the relationship between short term increases in BMI following ART and risk of CVD or type II diabetes in over 9000 people enrolled in the international, prospective, multi-cohort D:A:D study. They reported that for each unit of BMI increase within the first year following initiation of ART, the risk of CVD and diabetes significantly increased. However, the implications of these results depended on baseline BMI.

Selection criteria included being treatment naive when initiating ART and having BMI measurements within the previous year and after one year [+/- 6 months] following ART initiation. The outcomes for the study were new CVD [myocardial infarction, invasive cardiovascular procedures or stroke] and diabetes events. Exclusion criteria included pre-existing CVD or diabetes. The study comprised 9,321 people, who were stratified according to their pre-ART BMI as under weight (< 18.5 kg/m2), normal (18.5 – 25), over weight (25 – 30) or obese (> 30). Poisson regression models were used to determine the risk of CVD or diabetes according to one-year change in BMI, stratified by pre-ART BMI category, cohort and established CVD and diabetes risk factors and calendar year.

Most people fell into the two middle BMI stratifications: normal weight (64%), and overweight (23%). While only small numbers fell into the two extreme BMI groups: initially underweight (6%) and obese (6%). Three quarters of the cohort were male and half were men who have sex with men (MSM). Smoking inversely correlated with baseline BMI.

After one year of ART, the mean increase in BMI was +0.67 kg/m2. Baseline BMI was strongly related to response with mean changes of +1.82, +0.77, +0.30 and -0.01 in the underweight, normal, overweight and obese groups respectively. This trend continued with mean changes at 5 years of +2.5, +1.38, +0.73 and +0.14 in the same groups respectively. The underweight group gained the most BMI and the obese group remaining stable or loosing weight. Overall, the percentage of overweight or obese cohort subjects increased from 29.6% before ART to 35.5% during ART.

A total of 97 [1.0%] CVD events were reported during 43,982 person years (PY) with an incidence of 2.21/1000 PY [95% CI: 1.76 – 2.68]. Pre-ART BMI was positively related to CVD event rate (95%CI) per 1000 PY: 1.73 (0.56 – 4.03), 2.13 (1.63 – 2.73), 2.41 (1.55 – 3.59) and 2.78 (1.12 – 5.74) in the under, normal, over and obese groups respectively.

However, when the risk of CVD was assessed according to the increase in BMI units, the normal weight group had the highest risk [incidence risk ratio (IRR) 1.18 (CI: 1.04 – 1.32), p=0.01]. This translates to an 18% increased risk of CVD per unit of BMI gained for the normal group. In contrast, there was no effect on the risk of CVD from increased BMI for the obese group [IRR: 1.08 (0.71 – 1.64), p=0.714], the overweight group [IRR 0.80 (0.62 – 1.02), p=0.070] or the underweight group [IRR 0.92 (0.54 – 1.56), p=0.792].

Analysis by pre-ART BMI (to work with even distribution) only showed higher CVD rate for the middle two quartiles [20.9 – 23.0 and 23.0 – 25.5] when adjusted for both demographics and all time-updated variables.

Type-2 diabetes developed in 125 patients (1.4%) during 43,278 PY, with a rate of 2.89 per 1000 PY. Similar to CVD, when stratified according to pre-ART BMI group, the rate of diabetes also appeared to be related to higher BMI, with the highest rates in the obese group [IRR 9.97 (95%CI: 6.32 – 14.96)] and the overweight group [IRR 4.05 (95%CI: 2.88 – 5.54)], and the lowest rates in the underweight group [IRR 2.04 (95%CI: 0.76 – 4.53)] and the normal group [IRR 2.01 (95%CI: 1.51 – 2.59)]. When the risk of diabetes was assessed according to the increase in BMI units after one year of ART, there was an approximately 20% elevated risk of diabetes per unit gain in BMI for those with normal BMI before ART [IRR 1.19 (95%CI: 1.06 – 1.33)] and those overweight [IRR 1.22 (95%CI: 1.06 – 1.40)]. There was not a significant increase in diabetes risk per unit of BMI gained in the underweight or obese groups. In all groups taken together, there was a 10-11% increase in risk for diabetes associated with each unit gain in BMI. This result did not change by categorising pre-ART BMI groups according to quartiles.

The researchers conclude that short-term gains in BMI after ART could be associated with increased risk of CVD, mostly in people with normal/intermediate levels of BMI before ART and that increases in BMI are associated with higher risk of diabetes in all groups. They urge caution in the interpretation of the result that there was no change of CVD risk with gain in BMI for the high BMI pre-ART group, as the sample size was low and BMI may not be the best predictor of CVD.

Reference:

Achhra AC et al. Impact of short-term change in body mass index after antiretroviral therapy initiation on subsequent risk of cardiovascular disease and diabetes in HIV-positive individuals: the D:A:D study. 20th International AIDS Conference, 20-25 July 2014, Melbourne. Oral abstract WEAB0103.
http://pag.aids2014.org/Abstracts.aspx?SID=1141&AID=6485 (abstract)
http://pag.aids2014.org/flash.aspx?pid=1405 (webcast)

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