Current Atherosclerosis Reports

Lowering blood pressure (BP) reduces the risk of major cardiovascular mortality and morbidity. Current consensus targets for BP reduction are less than 140/90 mm Hg in uncomplicated hypertension and less than 130/80 mm Hg in those patients with diabetes, chronic kidney disease, and coronary artery disease or in those who are at high risk for developing coronary artery disease (defined as a Framingham risk score of ≥ 10%). There is solid epidemiologic evidence for lower BP targets, supported by some clinical studies with surrogate end points. On the other hand, there are meager data from clinical trials using hard end points, and there is a concern that overly aggressive BP lowering, especially of diastolic BP, may impair coronary perfusion, particularly in patients with left ventricular hypertrophy and/or coronary artery disease. This review evaluates the evidence for the benefit of lower BP targets in hypertension management.

Atherosclerosis is the leading cause of morbidity and mortality in the United States. Evidence suggests that antioxidants, especially α-tocopherol (AT), have potential benefits with respect to cardiovascular disease. AT has been shown to decrease lipid peroxidation, to inhibit platelet adhesion, aggregation, and smooth muscle cell proliferation, to exert anti-inflammatory effects on monocytes, and to improve endothelial function. Low levels of AT are related to a higher incidence of cardiovascular disease and increased intakes appear to afford protection against cardiovascular disease. Although clinical trials with AT supplementation to date have been conflicting, the majority of evidence supports a benefit for AT supplementation in patients with pre-existing cardiovascular disease. Clearly, more clinical trials are required in individuals with increased oxidative stress before a definitive recommendation can be made with respect to AT supplementation in atherosclerosis.

This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD =  − 0.06, 95% CI =  − 0.19; 0.06 and SMD = 0.26, 95% CI =  − 0.66; 1.19), but significantly different (p-value = 0.04). Meta-regression and subgroup analyses did not show any significant differences in pooled estimates across covariates. The effect of statins on CAC differs across study designs. OSs demonstrate associations between statin use and higher CAC scores and presence while being prone to confounding by indication. Effects from RCTs do not reach statistical significance and vary depending on the quantification method, hampering drawing conclusions. Further investigations are required to address the limitations inherent in each approach.

Low-density lipoprotein cholesterol (LDL-C) plays a central role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Statins are the cornerstone of therapy for the treatment of elevated LDL-C and for the primary and secondary prevention of ASCVD. However, some patients are intolerant of statins or are unable to achieve acceptable lipid levels on statin-based regimens alone. Proprotein convertase subtilisin/kexin type 9 (PCSK9) serves as an important regulator of hepatocyte LDL receptor expression and degradation, and recent genetic studies have highlighted the critical role of PCSK9 in human disease. Gain-of-function mutations in PCSK9 are associated with familial hypercholesterolemia, whereas loss-of-function mutations are protective against ASCVD. Therefore, PCSK9 inhibition offers a promising supplement or alternative to statin therapy in the reduction of LDL-C. Numerous phase II and III randomized control trials have demonstrated the tolerability of monoclonal antibodies against PCSK9 and their efficacy in lowering LDL-C by an additional 40–70 %. In this article, we review the growing role of PSCK9 inhibition in LDL-C reduction for diverse patient populations.

There has been substantial progress toward understanding and investigating the specific genetic factors that influence interindividual variations in platelet-directed therapy. There has also been substantial progress toward better understanding of the pharmacogenetics of drug metabolism and phamacodynamic response to platelet antagonists. We summarize the relationship between genetic polymorphisms, response to platelet antagonists, and clinical impact on patient treatment for the commonly used antiplatelet drugs. The challenge faced in translating genotype identification into improved clinical outcomes reflects the complexity involved in the genomic influence on drug metabolism and activation.

The perceived association between dietary cholesterol (DC) and risk for coronary heart disease (CHD) has resulted in recommendations of no more than 300 mg/d for healthy persons in the United States. These dietary recommendations proposed in the 1960s had little scientific evidence other than the known association between saturated fat and cholesterol and animal studies where cholesterol was fed in amounts far exceeding normal intakes. In contrast, European countries, Asian countries, and Canada do not have an upper limit for DC. Further, current epidemiologic data have clearly demonstrated that increasing concentrations of DC are not correlated with increased risk for CHD. Clinical studies have shown that even if DC may increase plasma low-density lipoprotein (LDL) cholesterol in certain individuals (hyper-responders), this is always accompanied by increases in high-density lipoprotein (HDL) cholesterol, so the LDL/HDL cholesterol ratio is maintained. More importantly, DC reduces circulating levels of small, dense LDL particles, a well-defined risk factor for CHD. This article presents recent evidence from human studies documenting the lack of effect of DC on CHD risk, suggesting that guidelines for DC should be revisited.

MicroRNAs (miRs) are short non-coding RNA molecules involved in post-transcriptional gene regulation by binding to the 3′ untranslated region of a messenger RNA (mRNA), thereby inhibiting the translation or inducing mRNA destabilization. MiRs are generally considered to act as intracellular mediators essential for normal cardiac function, and their deregulated expression profiles have been associated with cardiovascular diseases. Recent studies have revealed the existence of freely circulating miRs in human peripheral blood, which are present in a stable nature. This has raised the possibility that miRs may be released in the circulation and can serve as novel diagnostic markers for acute or chronic human disorders, including myocardial infarction (MI). This review summarizes the recent findings of miRs that fulfill the criteria of candidate biomarkers for MI.

Heart failure (HF) treatment paradigms increasingly recognize the importance of primary prevention. This review explores factors that enhance HF risk, summarizes evidence supporting the pharmacologic primary prevention of HF, and notes barriers to the implementation of primary prevention of HF with a focus on female and sexual and gender minority patients. HF has pathophysiologic sex-specific distinctions, suggesting that sex-specific preventive strategies may be beneficial. Pharmacologic agents that have shown benefit in reducing the risk of HF address the pathobiology underpinning these sex-specific risk factors. The implementation of pharmacologic therapies for primary prevention of HF needs to consider a risk-based model. Current pharmacotherapies hold mechanistic promise for the primary prevention of HF in females and gender and sexual minorities, although research is needed to understand the specific populations most likely to benefit. There are significant systemic barriers to the equitable provision of HF primary prevention.