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.................................................................................................................................... the associated absolute increase in risk for a given increment in TC is larger with increasing age.217

9.3.1 Effects of statins in primary and secondary prevention The use of statin therapy declines with increasing age, reflecting differences in both prescription and compliance.395,396 This trend is even more prominent among older patients who do not have evidence of occlusive vascular disease.396 One explanation for this pattern may be uncertainty about the effects of statins in older people due to the relatively small number of people aged >75 years who have been included in statin trials.233,397,398 The CTT collaboration recently provided a comprehensive assessment of the randomized evidence on the effects of statin therapy at different ages.217 Among 186 854 participants in 28 trials, 14 483 (8%) were aged >75 years at randomization. Overall, statin therapy produced a 21% relative reduction in major vascular events (relative risk 0.79, 95% CI 0.770.81) per 1.0 mmol/L reduction in LDL-C, and there was direct evidence of benefit among those aged >75 years. The relative reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease, but appeared smaller among older individuals not known to have vascular disease. Therefore, the available evidence from trials indicates that statin therapy produces significant reductions in major vascular events irrespective of age. However, there is less direct evidence of benefit among patients aged >75 years who do not already have evidence of occlusive vascular disease, and this limitation is currently being addressed by the STAtin therapy for Reducing Events in the Elderly (STAREE) trial in Australia.

9.3.2 Adverse effects, interactions, and adherence The safety and adverse effects of statins are a matter of special concern in older adults because they often have comorbidities, take multiple medications, and have altered pharmacokinetics and pharmacodynamics. Statindrug interactions are a concern, primarily because of their potential to increase muscle-related statin-associated adverse effects such as myalgia without CK elevation, myopathy with CK elevation, and the rare but serious rhabdomyolysis. It is recommended that a statin is started at a low dose if there is significant renal impairment and/or the potential for drug interactions, and then titrated upwards to achieve LDL-C treatment goals. The recommendations for the treatment of dyslipidaemias in older people are shown below. 9.4 Diabetes and metabolic syndrome

The number of people with DM will increase from 415 million today up to 550 million by 2030, but the situation may get even worse.399 Despite significant advantages in the management strategies that lessen atherosclerotic CVD risk factors, CVD has remained the leading cause of morbidity and mortality in patients with T2DM. The good news is that fatal CVD outcomes have declined significantly in both T1DM and T2DM between 1998 and 2014.400 DM itself is an independent risk factor for CVD and is associated with a higher risk of CVD, even more so in women. The difference in CVD risk between individuals with and without DM has narrowed substantially over the last few decades,401 and there are strong associations between DM and vascular outcomes.402,403 Recent data indicate that DM per se increases CVD risk about two-fold on average, but the risk is subject to wide variation depending on the population and current aggressive prophylactic therapy.401,404 Importantly, those with DM and CAD are at substantially higher CVD risk for future events. In T2DM, the risk of ASCVD is strongly determined by the presence of target organ damage—including nephropathy (microalbuminuria), neuropathy, or retinopathy—with the risks increasing in relation to the number of conditions present.405 Hypertension, dyslipidaemia, abdominal obesity, and non-alcoholic fatty liver disease (NAFLD) commonly coexist with T2DM and further aggravate the risk, which is highest in people with T2DM and multiple cardiometabolic risk factors.406408 Importantly, DM confers excess mortality risk following ACS despite modern therapies, highlighting the poor prognosis of coronary patients with T2DM and the need for intensive therapy.409 How to capture the extra risk beyond the traditional risk factors in clinical practice is a debated issue. A practical approach is that if one component is identified, a systematic search should be made for the others.410

9.4.1 Specific features of dyslipidaemia in insulin resistance and type 2 diabetes mellitus Diabetic dyslipidaemia is a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. The increase in large VLDL particles in T2DM initiates a sequence of events that generates atherogenic remnants, small dense LDL, and small TGrich dense HDL particles.411 These components are not isolated abnormalities but are closely linked to each other. Both LDL and HDL particles show variable compositional changes that are reflected in their functions. Notably, ApoC-III levels are increased in people with T2DM.412 High ApoC-III concentrations prevent

Recommendations for the treatment of dyslipidaemias in older people (aged >65 years)

Recommendations Classa Levelb Treatment with statins is recommended for older people with ASCVD in the same way as for younger patients.217 I A Treatment with statins is recommended for primary prevention, according to the level of risk, in older people aged <_75 years.217 I A Initiation of statin treatment for primary prevention in older people aged >75 years may be considered, if at high-risk or above.217 IIb B It is recommended that the statin is started at a low dose if there is significant renal impairment and/or the potential for drug interactions, and then titrated upwards to achieve LDL-C treatment goals. I C

ASCVD = atherosclerotic cardiovascular disease; LDL-C = low-density lipoprotein cholesterol. aClass of recommendation. bLevel of evidence. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026