Gender differences in use of cardiovascular disease-related interventions: D:A:D study

Polly Clayden, HIV i-Base

Use of most cardiovascular disease (CVD) interventions was lower among women than men in the D:A:D study, according to data presented at the 2014 HIV Drug Therapy Glasgow Congress.

There is limited data on potential gender differences in the use of interventions to prevent and treat CVD in HIV positive people. D:A:D is an observational study of more than 49,000 people with HIV from 11 cohorts in Europe, Australia and the USA, set up to investigate associations between antiretroviral use and CVD. Data are collected prospectively.

D:A:D investigators evaluated whether gender differences exist among the study participants. Camilla Ingrid Hatleberg presented findings on behalf of the D:A:D group.

The investigators looked at the use of: lipid lowering drugs (LLDs), angiotensin converting enzyme inhibitors (ACEIs), anti-hypertensives and invasive cardiovascular procedures (ICPs).

Follow-up in the gender study was from 1 February 1999 until 1 February 2013. People with myocardial infarction (MI) or stroke at baseline (gender study entry) were excluded.

The investigators calculated the rates of initiation of CVD interventions for the whole period of follow-up and for circumstances when people are known to be at higher CVD risk according to subgroups: 1) total cholesterol >6.2 mmol/L, 2) triglyceride >2.3 mmol/L, 3) hypertension, 4) previous MI, 5) diabetes, 6) age >50 years, 7) predicted 10-year Framington CVD risk score >10%. Poisson regression was used to assess whether initiation rates were higher in men than women, after adjusting for potential confounding.

The number of women in D:A:D was considerably lower than the number of men, 13,039 vs 36,664; and they were younger, median 34 vs 39 years, and less likely to smoke, 29 vs 39%, than men; all comparisons p=0.0001.

The total follow up time spent in one of the seven high risk subgroups was longer for men than women: 269,705 vs 97, 065 person years spent (PYS). Men spent a greater proportion of time with high triglycerides, 30.1 vs 15.3%; being over 50 years, 28.9 vs 15.3%; and with high CVD risk score, 25.6 vs 4.1%.

Women spent the largest proportions of time at risk with high trigycerides, hypertension and being over 50 years, all approx 15%.

Overall, women received ICPs at a rate of 0.07/100 person-years (PYRS) compared to 0.29/100 PYRS in men. The rates of initiation of LLDs (1.28 vs 2.46), anti-hypertensives (1.11 vs 1.38) and ACEIs (0.82 vs 1.37) were all significantly lower in women than men, p=0.001. But in the group of women with established high CVD risk scores, initiation of all LLDs was slightly higher in women than men. Rates of initiation of anti-hypertensives and ACEIs were slightly higher in women than men for women with previous MI; and rates of initiation of anti-hypertensives were slightly higher in women with hypertension.

Unadjusted relative rate (RR) of receipt of the four types of interventions between women and men: LLDs 0.52 (95% CI 0.49 – 0.56); ACEIs 0.60 (95% CI 0.56 – 0.65); anti-hypertensives 0.83 (95% CI 0.78 – 0.89); and ICPS 0.25 (95% CI 0.20 – 0.32) (all comparisons p=0.0001).

Once adjusted for potential confounders (age, calendar year, BMI, total cholesterol, triglycerides, hypertension, previous MI, diabetes, and moderate/high predicted 10 year CVD risk score) RR for receipt of all interventions except anti-hypertensives were attenuated but remained significantly lower in women than men. Adjusted RR: LLDs 0.80 (95% CI 0.75 – 0.86); ACEIs 0.80 (95% CI 0.74 – 0.87); and ICPS 0.49 (95% CI 0.38 – 0.63), all comparisons p=0.0001.

After adjustment the RR for anti-hypertensives shifted from a lower to higher rate in women: 1.21 (95% CI 1.13 – 1.30), p=0.0001. Dr Hatleberg remarked that this phenomenon was driven mainly by hypertension itself and CVD risk score >10%.

These RR remained after sensitivity analyses adjusting for ethnicity, smoking, AIDS, CVD family history and stroke, and with total cholesterol, triglycerides and blood pressure as continuous covariates.

Dr Hatleberg concluded that action should be taken to ensure HIV positive women and men are properly monitored for CVD and receive appropriate interventions. She suggested that women might be monitored less frequently as guidelines focus on moderate/high risk and they are more likely to be low CVD risk.


Hatleberg CI et al. Gender differences in HIV-positive persons in use of cardiovascular disease-related interventions: D:A:D study. HIV Drug Therapy Glasgow Congress, 2-6 November 2014. Oral abstract O324. Journal of the International AIDS Society 2014, 17(Suppl 3):19516

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