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Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in women, yet it remains underdiagnosed, undertreated, and understudied in women compared with men. Although estrogen has provided observational evidence of cardioprotection, randomized controlled trials using hormone replacement therapy have generally produced unfavorable results. For this narrative review, a literature search was performed using the key words cardiovascular disease, women, and dyslipidemia in PubMed and Google Scholar with no date limitations. References within each article were also reviewed for additional relevant articles. Sex-specific risk factors and underrecognized conditions more predominant in women elevate ASCVD risk, creating further clinical challenges, such as the need for accurate risk stratification, compared with in men. Dyslipidemia frequently manifests or worsens during the menopausal transition. Therefore, identification during midlife and implementing lipid-lowering strategies to reduce ASCVD risk is imperative. Women have historically been poorly represented in cardiovascular (CV) outcome trials. However, more recent studies and meta-analyses have indicated that lipid-lowering therapies are equally effective in women and produce similar reductions in CV events and total mortality. Major cholesterol guidelines address many of the challenges that clinicians face when assessing ASCVD risk in women. Key points specific to women include obtaining a detailed history of pregnancy-related conditions, identification of common autoimmune disorders associated with systemic inflammation, and use of 10-year ASCVD risk calculators and imaging modalities (coronary artery calcium) to optimize ASCVD assessment. In terms of treatment, similar to men, women with existing ASCVD or high-risk primary prevention patients should be treated aggressively to achieve ≥50% LDL-C reductions and/or LDL-C goals as low as <55 mg/dL. Appropriate lipid-lowering therapies include high-intensity statins with or without ezetimibe and proprotein convertase subtilisin kexin/type 9 inhibitors. Women with lower ASCVD risk may be considered for low- to moderate-intensity statin therapy (approximately 30%-50% LDL-C reduction). All women, regardless of ASCVD risk category, should implement therapeutic lifestyle changes, which improve many common age-related cardiometabolic conditions. Although ASCVD and current risk factor trends in women are concerning, numerous evidence-based approaches are available to protect women with ASCVD risk from life-changing CV events.

The US dietary supplement (DS) market has expanded exponentially since 1994, with an estimated 50,000–80,000 individual products currently available. Many DS claim cholesterol or cardiovascular benefits. Overall, well-designed randomized controlled trials (RCTs) with DS are lacking, while studies with favorable results are commonly performed outside of the USA, resulting in inconsistent findings. The expansion of the DS market has limited the ability of the Food and Drug Administration to regulate and prevent substandard products. Eicosapentaenoic acid and docosahexaenoic acid are components of DS fish oil. Recent RCTs utilizing prescription fish oil have provided mixed findings and small but significant safety concerns. Hence, the role of DS fish oil is limited and no longer recommended by major cardiovascular guidelines. Concerns have also been observed from RCTs utilizing prescription niacin, resulting in a negligible role for DS niacin in lipid management. Red yeast rice has demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions in studies performed worldwide, including the USA. However, quality concerns and inconsistent study results have been reported on multiple occasions. Other common DS have produced modest reductions in LDL-C and may provide other cardiometabolic benefits, including garlic, phytosterols, psyllium, and berberine. Yet inconsistent study results and quality concerns continue to be reported for most. Nonetheless, there is a need for alternative therapies that can safely and effectively reduce cardiovascular risk. However, until DS routinely match label claims and are free of contaminants, the agents have a limited role in clinical practice.

An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence. To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations. Literature was obtained from MEDLINE (1966 - June 2005) and references from selected articles. A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising. Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy.

Policosanol is a poorly absorbed nutritional supplement used primarily for cholesterol management. Findings from previous trials evaluating the effects of policosanol are mixed with early data reporting positive lipid effects while more recent studies indicate negligible efficacy. We hypothesized that re-formulating policosanol would result in an improvement in major lipoproteins and possibly provide some explanation for previously conflicting trial data. Our primary objectives were to assess the efficacy and safety of modified-policosanol (MP) on the major lipoproteins among hyperlipidemic subjects receiving background statin therapy or as monotherapy. This 8-week clinical trial consisted of 3 arms. Subjects receiving chronic statin therapy ( N  = 36) were randomized in a double-blind design to MP 20 mg daily or placebo. In the third arm, subjects not receiving statin therapy ( N  = 18) were assigned open-label MP 20 mg daily. The utilization of MP when added to background statin therapy or as monotherapy resulted in no significant changes in major lipoproteins (all p  > 0.05). The MP therapy was well tolerated with no major adverse events reported. Consistent with recent clinical trial data, MP demonstrated an excellent safety profile but produced no significant effects on major lipoproteins when used as monotherapy or when given with concomitant statin therapy.

Isolated asymptomatic glycerol kinase deficiency (GKD) or 'pseudohypertriglyceridemia', is an X-linked recessive disorder resulting in hyperglyceroluria and hyperglycerolemia. Patients typically present with hypertriglyceridemia, which is unresponsive to therapy. The falsely elevated triglycerides are a result of clinical laboratories utilizing glycerol levels to report triglyceride concentrations. Glycerol blanking will account for the excess glycerol and provide accurate triglyceride measures. Pseudohypertriglyceridemia is linked to glucose impairment and other forms of GKD involving childhood metabolic crises and developmental limitations. Identifying patients with pseudohypertriglyceridemia prevents overestimation of cardiovascular risk and exposure to unnecessary lipid-altering agents; and heightens the awareness of the potential for symptomatic GKD in male offspring. We urge clinical labs to provide a glycerol-blanked triglyceride measurement for known or suspected pseudohypertriglyceridemia.

A 52-year-old man with a longstanding history of hypertriglyceridaemia (approximately 7 mmol/L (600 mg/dL)), unresponsive to treatment, presented to a lipid-specialty clinic. Additional triglyceride-lowering therapies were added with no effect. It was then noted that despite the apparent hypertriglyceridaemia, his serum sample was clear. A ‘glycerol blank’ was then requested from an advanced lipid laboratory, which reported a triglyceride value of 0.7 mmol/L (62 mg/dL). These findings suggest isolated asymptomatic glycerol kinase deficiency (GKD) or ‘pseudohypertriglyceridaemia’. The falsely elevated triglyceride values in such individuals are a result of excess serum glycerol and clinical laboratories measuring glycerol to report triglyceride concentrations. After discontinuation or modification of the patient's primary triglyceride-lowering agents, the lipid panels and triglyceride values remained comparable to previous readings. Recognition of asymptomatic GKD is important to prevent unnecessary treatment and overestimated cardiovascular risk.

Mipomersen (Kynamro® [mipomersen sodium injection]; Genzyme, a Sanofi Company, MA, USA) is indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apoB, total cholesterol and non-HDL cholesterol in patients with homozygous familial hypercholesterolemia. In a 6-month Phase III trial (n = 51), mean percent change in LDL-C was -25% (95% CI: -32 to -18) versus placebo -3% (95% CI: -12 to 5; p < 0.001). The absolute mean LDL-C reduction was 113 mg/dl (2.92 mmol/l). Lipoprotein(a) was also significantly lowered by -31% (95% CI: -39 to -23) versus placebo -8% (95% CI: -19 to 3; p < 0.01). Some patients experienced transient and generally reversible hepatic effects, mild-to-moderate injection site reactions and flu-like symptoms. The mechanism of action and metabolism of mipomersen makes drug-drug interactions unlikely.

High-elevation ecosystems are among the few ecosystems worldwide that are not yet heavily invaded by non-native plants. This is expected to change as species expand their range limits upwards to fill their climatic niches and respond to ongoing anthropogenic disturbances. Yet, whether and how quickly these changes are happening has only been assessed in a few isolated cases. Starting in 2007, we conducted repeated surveys of non-native plant distributions along mountain roads in 11 regions from 5 continents. We show that over a 5- to 10-year period, the number of non-native species increased on average by approximately 16% per decade across regions. The direction and magnitude of upper range limit shifts depended on elevation across all regions. Supported by a null-model approach accounting for range changes expected by chance alone, we found greater than expected upward shifts at lower/mid elevations in at least seven regions. After accounting for elevation dependence, significant average upward shifts were detected in a further three regions (revealing evidence for upward shifts in 10 of 11 regions). Together, our results show that mountain environments are becoming increasingly exposed to biological invasions, emphasizing the need to monitor and prevent potential biosecurity issues emerging in high-elevation ecosystems. The authors resurveyed a previously sampled set of mountain transects on five continents, showing that the ranges of non-native plant species have shifted upslope in most locations in just 5–10 years.

BackgroundT1 rectal cancer (RC) patients are increasingly being treated by local resection alone but uniform surveillance strategies thereafter are lacking. To determine whether different local resection techniques influence the risk of recurrence and cancer-related mortality, a meta-analysis was performed.MethodsA systematic search was conducted for T1RC patients treated with local surgical resection. The primary outcome was the risk of RC recurrence and RC-related mortality. Pooled estimates were calculated using mixed-effect logistic regression. We also systematically searched and evaluated endoscopically treated T1RC patients in a similar manner.ResultsIn 2585 unique T1RC patients (86 studies) undergoing local surgical resection, the overall pooled cumulative incidence of recurrence was 9.1% (302 events, 95% CI 7.3–11.4%; I2 = 68.3%). In meta-regression, the recurrence risk was associated with histological risk status (p < 0.005; low-risk 6.6%, 95% CI 4.4–9.7% vs. high-risk 28.2%, 95% CI 19–39.7%) and local surgical resection technique (p < 0.005; TEM/TAMIS 7.7%, 95% CI 5.3–11.0% vs. other local surgical excisions 10.8%, 95% CI 6.7–16.8%). In 641 unique T1RC patients treated with flexible endoscopic excision (16 studies), the risk of recurrence (7.7%, 95% CI 5.2–11.2%), cancer-related mortality (2.3%, 95% CI 1.1–4.9), and cancer-related mortality among patients with recurrence (30.0%, 95% CI 14.7–49.4%) were comparable to outcomes after TEM/TAMIS (risk of recurrence 7.7%, 95% CI 5.3–11.0%, cancer-related mortality 2.8%, 95% CI 1.2–6.2% and among patients with recurrence 35.6%, 95% CI 21.9–51.2%).ConclusionsPatients with T1 rectal cancer may have a significantly lower recurrence risk after TEM/TAMIS compared to other local surgical resection techniques. After TEM/TAMIS and endoscopic resection the recurrence risk, cancer-related mortality and cancer-related mortality among patients with recurrence were comparable. Recurrence was mainly dependent on histological risk status.

Transcatheter aortic valve implantation (TAVI) has shown similar or improved clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis at low risk for surgical mortality. This cost-utility analysis compared TAVI with SAPIEN 3 versus SAVR in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of the Swedish healthcare system. A published, two-stage, Markov-based cost-utility model that captured clinical outcomes from the (SWEDEHEART) registry (2018-2020) was adapted from the perspective of the Swedish healthcare system using local general population mortality, utility and costs data. The model had a lifetime horizon. Model outputs included changes in direct healthcare costs and health-related quality of life from using TAVI as compared with SAVR. TAVI with SAPIEN 3 resulted in lifetime costs per patient of 484,142 SEK Swedish krona (SEK) and lifetime quality-adjusted life years (QALYs) per patient of 7.16, whilst SAVR resulted in lifetime costs and QALYs per patient of 457,625 SEK and 6.81 QALYs, respectively. Compared with SAVR, TAVI offered an incremental improvement of +0.35 QALY per patient at an increased cost of +26,517 SEK per patient over a lifetime horizon, resulting in an incremental cost-effectiveness ratio of 76,532 SEK per QALY gained. TAVI with SAPIEN 3 is a cost-effective option versus SAVR for patients with symptomatic severe aortic stenosis at low risk for surgical mortality treated in the Swedish healthcare setting. These findings may inform policy decisions in Sweden for the management of this patient group.