Summary: Background: Peripheral artery disease (PAD) affects more than 202 million people worldwide. Several studies have shown that patients with PAD are often undertreated, and that statin utilization is suboptimal. European and American guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on lower extremities PAD endpoints and examine whether statin dose (high vs. low intensity) impacts outcomes. Patients and methods: We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of use of statins vs. no statins for PAD patients or studies comparing high vs. low intensity statins were considered to be potentially eligible. We excluded studies with only critical limb threatening ischemia (CLTI) patients. The Medline (PubMed) database was searched up to January 31, 2021. A random effects meta-analysis was performed. Results: In total, 39 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) patients were on statins vs. 139,645 (50.66%) who were not on statins. Statin use was associated with a reduction in all cause-mortality by 42% (HR: 0.58, 95% CI: 0.49–0.67, p<0.01) and cardiovascular death by 43% (HR: 0.57, 95% CI: 0.40–0.74, p<0.01). Statin use was associated with an increase in amputation-free survival by 56% (HR: 0.44, 95% CI: 0.30–0.58, p<0.01). The risk of amputation and loss of patency were reduced by 35% (HR: 0.65, 95% CI: 0.41–0.89, p<0.01) and 46% (HR: 0.54, 95% CI: 0.34–0.74, p<0.01), respectively. Statin use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR: 0.65, 95% CI: 0.51–0.80, p<0.01) and myocardial infarction rates by 41% (HR: 0.59, 95% CI: 0.33–0.86, p<0.01). Among patients treated with statins, the high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR: 0.64, 95% CI: 0.54–0.74, p<0.01) compared to patients treated with low intensity statins. Conclusions: Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MACE, risk for amputation, or loss of patency. Higher statin dose seems to be associated with improved outcomes.

Tea is one of the most-widely consumed beverages in the world with a number of different beneficial health effects, mainly ascribed to the polyphenolic content of the tea catechins. The aim of this study was to examine the consumption of green, black, or no tea, in relation to the previously validated successful ageing index (SAI; higher values “healthier” ageing) in a combined analysis of adults aged >50 years old from the ATTICA (n = 1128 adults from Athens, Greece metropolitan area) and the MEDiterranean Islands Study (MEDIS) (n = 2221 adults from various Greek island and Mani) studies. After adjusting for age, sex, smoking, and coffee consumption, green tea was positively associated with SAI (b ± SE: 0.225 ± 0.055, p < 0.001), while black tea was negatively associated with SAI (unstandardized b coefficient ± Standard error: −0.807 ± 0.054, p < 0.001). Green tea (vs black tea) consumption, had higher odds of a SAI of over 3.58 out of 10 (OR: 1.77, 95% CI: 1.38–2.28). Green tea consumption was also associated with higher levels of physical activity (p < 0.001) and reduced likelihood of hypertension (p = 0.006) compared with black tea. Two possible mechanisms are that green tea possesses high levels of catechins such as (−)-epigallocatechin 3-gallate and l-theanine compared with black tea. Therefore, the present analysis supports both the role of green tea constituents in successful ageing, as well as its role as an important component of an overall healthy diet in adults aged 50 years and over from these two epidemiological studies.

Lipoprotein(a) [Lp(a)] is a well-established risk factor for cardiovascular disease, predisposing to major cardiovascular events, including coronary heart disease, stroke, aortic valve calcification and abdominal aortic aneurysm. Lp(a) is differentiated from other lipoprotein molecules through apolipoprotein(a), which possesses atherogenic and antithrombolytic properties attributed to its structure. Lp(a) levels are mostly genetically predetermined and influenced by the size of LPA gene variants, with smaller isoforms resulting in a greater synthesis rate of apo(a) and, ultimately, elevated Lp(a) levels. As a result, serum Lp(a) levels may highly vary from extremely low to extremely high. Hyperlipoproteinemia(a) is defined as Lp(a) levels > 30 mg/dL in the US and >50 mg/dL in Europe. Because of its association with CVD, Lp(a) levels should be measured at least once a lifetime in adults. The ultimate goal is to identify individuals with increased risk of CVD and intervene accordingly. Traditional pharmacological interventions like niacin, statins, ezetimibe, aspirin, PCSK-9 inhibitors, mipomersen, estrogens and CETP inhibitors have not yet yielded satisfactory results. The mean Lp(a) reduction, if any, is barely 50% for all agents, with statins increasing Lp(a) levels, whereas a reduction of 80–90% appears to be required to achieve a significant decrease in major cardiovascular events. Novel RNA-interfering agents that specifically target hepatocytes are aimed in this direction. Pelacarsen is an antisense oligonucleotide, while olpasiran, LY3819469 and SLN360 are small interfering RNAs, all conjugated with a N-acetylgalactosamine molecule. Their ultimate objective is to genetically silence LPA, reduce apo(a) production and lower serum Lp(a) levels. Evidence thus so far demonstrates that monthly subcutaneous administration of a single dose yields optimal results with persisting substantial reductions in Lp(a) levels, potentially enhancing CVD risk reduction. The Lp(a) reduction achieved with novel RNA agents may exceed 95%. The results of ongoing and future clinical trials are eagerly anticipated, and it is hoped that guidelines for the tailored management of Lp(a) levels with these novel agents may not be far off.