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14th July 2022
Arterial stiffness progression, based on measurement of brachial-ankle pulse wave velocity, is slower among patients at high atherosclerotic risk who are prescribed statin drugs according to the findings of retrospective cohort study by Chinese researchers.
The term ‘arterial stiffness’ refers to the loss of elasticity in the walls of large arteries, especially the aorta, over time and results from a degenerative process affecting mainly the extracellular matrix as a result of aging and other risk factors. Moreover, arterial stiffness and wave reflections are now well accepted as the most important determinants of increasing systolic and pulse pressures in aging societies and increasingly used in the clinical assessment of patients with hypertension and various cardiovascular risk factors. The use of brachial-ankle pulse wave velocity, which can be used to non-invasively assess arterial stiffness progression, has been proposed as a surrogate end point for cardiovascular disease and a systematic review in 2012 found that an increase in brachial-ankle pulse wave velocity by 1 m/s corresponded with an increase of total cardiovascular events, cardiovascular mortality, and all-cause mortality.
Patients at a high risk of atherosclerotic disease are usually prescribed statin therapy although whether these drugs can reduce or prevent the development of arterial stiffness is unclear. For example, one analysis concluded that statin therapy had a beneficial effect on aortic arterial stiffness. In contrast, another study revealed how the use of atorvastatin actually increased arterial stiffness. Nonetheless, in many cases, the currently available studies included a low number of patients or were undertaken over a short period of time.
For the present study, the Chinese team retrospectively examined the relationship between statin use and the progression of arterial stiffness, based on measurement of brachial-ankle pulse wave velocity. The researchers used data from the Kailuan study which is a large, prospective study including over 100,000 individuals. A wide range of data was collected during the study including demographic and socioeconomic information, e.g., education level, average income of each family member as well as medical and lifestyle measures such as physical activity. Since 2010, individuals within the study at a high risk of peripheral artery disease, i.e., those with at least one risk factor such as hypertension or diabetes, were invited to have a baseline brachial-ankle pulse wave velocity (BaPWV) measurements and which was repeated at follow-up visits. The team included patients prescribed statins at least 6 months prior to their first BaPWV measurement. Furthermore, statin users were also divided into those who discontinued with their treatment within the first two years and those who had a high level of statin adherence. These statin users were then propensity matched with non-users.
Arterial stiffness and statin use
A total of 1310 individuals with a mean age of 64.6 years (75.7% male) using statins were propensity matched with the same number of non-statin users although the non-users had a slightly lower mean age (61.9 years).
The use of statins was associated with a significantly lower baseline BaPWV value compared to non-users (difference = -33.6 cm/s, 95% CI -62.1 to -5.1 cm/s).
During a mean follow-up of 4.8 years, the BaPWV increased from a mean of 1778.8 cm/s to 1831.9 cm/s in the statin group and from 1799 to 1870.8 in the non-statin group. Using a multivariable linear regression model, the authors found that statin use was associated with a significantly slower progression of BaPWV (difference = -23.3 cm/s/year).
They concluded that statin use appeared to be linked with a slowing of BaPWV progression in adults with a high atherosclerotic risk, suggesting that these drugs were able to prevent the development and worsening of subclinical cardiovascular lesions at an early stage.
Zhou YF et al. Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk JAMA Netw Open 2022
6th July 2022
Statin use as primary prevention against cardiovascular disease is associated with a significant reduction in the risk of hospitalisation and mortality among patients who become infected with COVID-19. This was the conclusion of a large, propensity-matched analysis of the French National Healthcare database by a team from the French National Agency for Medicines and Health Products Safety, Paris, France.
While the introduction of COVID-19 vaccines has significantly reduced both hospitalisation and mortality from COVID-19, prior to this drug repurposing was examined as a potential means for reducing the severity of infection and one class of drugs examined were the statins. There were good reasons to consider statins as potentially anti-viral agents because previous work had shown that in patients hospitalised with laboratory-confirmed seasonal influenza, statin treatment is associated with a 41% reduction in 30-day mortality. Moreover, other work found that cells treated with statins produced Ebola virus particles devoid of the surface glycoproteins required for virus infectivity.
There is already some evidence that among patients taking statins, there is a statistically significant decrease in the odds of in-hospital mortality in those with COVID-19. Nevertheless, this is not a consistent finding with other data has suggesting that the use of statins (in patients with type 2 diabetes) is associated with increased mortality among those hospitalised with COVID-19. Much of the research to date did not include a control group and for the present study, the French team identified patients aged 40 years and older, prescribed one of several statins (the exposed group) and propensity-matched these individuals based on age, gender, co-morbidities and sociodemographic factors (control group). But the team were also interested in whether there were differences between individual drugs within the class and if the intensity of therapy (e.g., low, moderate or high) impacted on either COVID-related hospitalisation or mortality. The primary outcome of the study was COVID-19-related hospitalisation and using Cox proportion hazard models, adjusted for several covariates e.g., age, gender, co-morbidities, the researchers calculated event rates between those using statins and the matched-control patients.
Statin use and COVID-19 hospitalisation
A total of 2,058249 patients with a mean age 68.7 years (46.6% male) taking statins were matched with the same of number of control patients. The most common co-morbidities were hypertension (41.8%) and diabetes (33.7%). There were a total of 9,396 hospitalisations for COVID-19, 4372 among those in the control group.
In fully adjusted models, patients in the statin group had a 16% lower risk of hospitalisation (hazard ratio, HR = 0.84, 95% CI 0.81 – 0.88, p < 0.0001). This relationship was maintained for the different agents within the class. For example, the risk was reduced by 25% for fluvastatin (HR = 0.75) and simvastatin (HR = 0.79). The relationship was also significant for low (e.g. fluvastatin 20/40 mg), medium (e.g., simvastatin 10 mg), not not for high (e.g., atorvastatin 40 or 80 mg) intensity therapy.
A similar reduction in risk was also evident for mortality among those taking statins (HR = 0.77, 95% CI 0.69 – 0.86). However, both atorvastatin and fluvastatin did not have a significant effect on mortality and as with hospitalisation, there was no significant effect for high intensity therapy on mortality.
The authors concluded that their data suggested a relatively small, but robust reduction in the risk of COVID-19-related hospitalisation and death among those prescribed statins before hospital admission.
Bouillon K et al. Association of Statins for Primary Prevention of Cardiovascular Diseases With Hospitalization for COVID‐19: A Nationwide Matched Population‐Based Cohort Study J Am Heart Assoc 2022