Atherosclerotic cardiovascular disease (ASCVD), the leading global cause of morbidity and mortality in the United States is largely attributed to a variety of cardiovascular risk factors, including hypertriglyceridemia, elevated low-density lipoprotein cholesterol (LDL-C), insulin resistance, hypertension and obesity.

Coronary heart disease (CHD) is the most common manifestation of cardiovascular disease (CVD), comprising approximately 50% of patients’ first CVD events.

 Risk factors include a family history of premature ASCVD (men <55 years old, women <65 years old), metabolic syndrome (increased body mass index, elevated triglycerides >150 mg/dL, elevated blood pressure), hypercholesterolemia and chronic kidney disease.

Risk of ASCVD is categorized as low (<5%), borderline (5%-<7.5), intermediate (> 7.5%-<20) or high (>20%) over a 10-year period.

 These risk stratifications can help determine the most appropriate interventions for patients. Those with minimal or borderline ASCVD risk may be eligible for lifestyle modifications, including dietary improvements, physical activity, and smoking cessation if applicable.

 In addition to lifestyle changes, several therapies are used to lower LDL-C and/or triglyceride levels, but only select agents have demonstrated a significant effect in reducing cardiovascular mortality

This article reviews the evolving therapeutic landscape for lowering LDL-C and cardiovascular risk, with an emphasis on the role of omega-3 fatty acids.

Cholesterol-lowering statin therapy is frequently used in patients with or without a history of CHD,

 primarily because of their ability to markedly lower LDL-C levels.

 These reductions in LDL-C levels are generally linearly related to the reductions in atherosclerotic plaques and atherosclerotic events (e.g., stroke or myocardial infarction).

Meta analyses suggest that statins reduce major adverse cardiovascular events1 and all-cause mortality in patients at risk for ASCVD.

 Additionally, reductions in LDL-C levels associated with the use of statins are generally irrespective of comorbidities, such as diabetes, chronic kidney disease or previous vascular disease.

The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend moderate or high intensity statins in addition to lifestyle modifications for those at moderate and high risk for recurring cardiovascular events.

THERAPEUTIC TARGETING OF HYPERTRIGLYCERIDEMIA

Beyond LDL-cholesterol lowering, therapeutic targeting of triglyceride levels can reduce cardiovascular risk,

as triglyceride levels of 150 mg/dL or more are considered a marker of persistent cardiovascular risk despite controlled LDL-C.

 In high-risk patients, such as those with established cardiovascular disease or diabetes, lowering triglyceride levels, along with decreasing LDL-C levels and raising HDL-C levels, produces trends suggesting reduced cardiovascular mortality.

 In addition to lifestyle changes, several therapies including ezetimibe, fibrates, and niacin; omega-3 fatty acids have been shown to lower triglyceride and non-HDL-C levels, but only select agents have demonstrated an effect in improving cardiovascular morbidity and mortality.

When ezetimibe therapy is added to statin or fibrate therapy, decreases in total cholesterol, LDL-C, and triglycerides, as well as increases in HDL-C levels, have been observed; however, the risk of cardiovascular events is only minimally improved and no effect on cardiovascular mortality has been observed.

Fibrate therapy has been associated with a 10% relative risk reduction for major cardiovascular events.

Although niacin, in combination with statin therapy, may increase in serum HDL-C levels, it does not reduce cardiovascular mortality or recurrent events in patients with/at high-risk for ASCVD.

As a class, omega-3 fatty acids (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]), have been shown to decrease triglyceride levels. Recent data on EPA/DHA combination regimens generally confer no evidence of a significant effect on cardiovascular disease composite end points or all-cause mortality.


THE CARDIOVASCULAR BENEFITS OF OMEGA-3 FATTY ACIDS

Another intervention that has shown efficacy toward lowering triglyceride levels is omega-3 fatty acids, which can be used for patients with high (200-499 mg/dL) or very high (≥500 mg/dL) triglyceride levels.

 Omega-3 fatty acid products are available as prescription or as dietary supplements.

 DHA and EPA are the primary long-chain fatty acids components of omega-3 fatty acids.

 The effects of omega-3 fatty acids on LDL-C vary based on the specific long-chain fatty acid (ie, DHA or EPA) component. Findings from a systematic review of head-to-head studies of omega-3 fatty acid products revealed that DHA increased LDL-C by 2.6%, whereas EPA decreased LDL-C by 0.7%.

Four FDA-approved omega-3 fatty acid therapies are currently available via prescription in the United States, and all are indicated to decrease triglyceride levels. They include omega-3 acid ethyl esters, omega-3 acid ethyl esters A, omega-carboxylic acids and icosapent ethyl (

Early studies, such as the GISSI-Prevenzione study, demonstrated reductions in cardiovascular events with omega-3 fatty acid supplements

; however, in the era of statin therapy, these results have generally not been replicated.

More recent studies have found that EPA/DHA combination products do not confer significant cardiovascular benefits.

 For example, the ASCEND trial evaluated the use of omega-3 fatty acids in 15 480 patients with type 2 diabetes. Patients were randomized to either 840 mg of omega-3 fatty acids (EPA, 460 mg; DHA, 380 mg) once daily or placebo. Compared with placebo, those in the omega-3 fatty acid group had no significant difference in the risk of serious vascular events.

 Additionally, the VITAL trial evaluated the use of vitamin D3 plus omega-3 fatty acids for the primary prevention of cardiovascular disease and cancer. Overall 25 871 patients were randomized to either vitamin D3 2000 IU plus omega-3 fatty acids (EPA, 460 mg; DHA, 380 mg) once daily or placebo. Use of omega-3 fatty acids did not result in a decreased incidence of either cardiovascular events or cancer.

Icosapent ethyl, the most recent product in the omega-3 landscape, is indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride levels and established CV disease or diabetes mellitus and two or more additional risk factors for CV disease. It is also indicated as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia.

Unlike other omega-3 fatty acid formulations that contain DHA and EPA, icosapent ethyl is a purified ethyl ester of EPA.

The approval of icosapent ethyl was based on data from the multicenter, randomized, double-blind REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention) trial that demonstrated a reduction in risk of ischemic events, including cardiovascular mortality, in patients receiving icosapent ethyl.

 Investigators evaluated the use of icosapent ethyl in patients with either (1) established cardiovascular disease or (2) diabetes and other risk factors who had triglyceride levels of 135-499 mg/dL and were currently receiving statin therapy.

Overall, 8,179 patients were randomized to statin plus icosapent ethyl 2 g twice daily (n = 4,089) or statin plus placebo (n = 4,090).

 The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization or unstable angina, while the secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke.

After a median of 4.9 years, patients randomized to statin plus icosapent had significantly fewer primary composite (17.2% versus 22%, respectively; 

<.001) and secondary composite events (11.2% versus 14.8%, respectively; 

<.001) versus those randomized to statin plus placebo.

 This represented a 25% relative risk reduction in primary composite end point of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.

 At a median follow-up of approximately 5 years, the number needed to treat to avoid one primary end point was 21.

Because some results from international trials have shown poorer outcomes in patients in the United States, a subgroup analysis of the US-only population (REDUCE-IT USA) was conducted.

 Primary and secondary composite events were significantly reduced in patients randomized to statin plus icosapent ethyl versus those randomized to statin plus placebo (

 In addition, the US population demonstrated particularly robust risk reductions across a variety of individual and composite end points, including cardiovascular death (

In the overall international population and in the US-only cohort, overall rates of adverse events, and serious adverse events leading to discontinuation did not significantly differ between groups.

 Icosapent ethyl was generally well tolerated and presented with no polypharmacy issues when combined with statins.

Following the REDUCE-IT findings, numerous guidelines were updated to include recommendations for the use of icosapent ethyl to reduce cardiovascular risks (

With the approval of icosapent ethyl, the role of omega-3 fatty acids in the evolving spectrum of ASCVD management and prevention is expanding. Moreover, the continued research and integration of icosapent ethyl in combination with other approaches could potentially reduce risks of CV events.

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Articles

This article reviews the evolving therapeutic landscape for lowering LDL-C and cardiovascular risk, with an emphasis on the role of omega-3 fatty acids.


New Approaches in Targeting Triglycerides for the Reduction of Cardiovascular Risks

The novel home rapid influenza diagnostic test (RIDT) Theraflu Home FluTest (THFT) demonstrated good sensitivity and specificity for influenza A and B viruses in a

presented at the American Thoracic Society 2020 Virtual meeting held August 5 to August 10, 2020.

Researchers from GSK and Ellume – the manufacturers of the THFT – conducted a prospective, multicenter study of 1012 participants between December 2018 and April 2019 from 25 sites in the US. Nasal swabs were self-collected or taken by caregivers from participants aged ≥2 years with influenza-like symptoms and analyzed using the THFT.

Key performance values were based on comparison with 3 reference methods: nucleic acid amplification testing, shell viral culture, and real-time polymerase chain reaction consensus comparator. Participants also completed a questionnaire regarding the ease of use of the THFT using a 5-point Likert scale (1=strongly disagree to 5=strongly agree).

, the THFT compared with the consensus result showed a positive agreement of 87.7% (95% confidence limits [CL] 83.6%-90.9%) and negative agreement of 98% (95% CL 96.6%-98.9%). 

, the THFT demonstrated a specificity of 97.9% (95% CL 96.8%-98.7%) vs the consensus result.

Also, because the sample of influenza B consisted of only 12 participants, a further analysis was conducted using 89 archived samples of influenza B. This analysis demonstrated a sensitivity vs consensus result of 86.3% (95% CL 74.3%-93.2%).

In the safety data set, 5 participants experienced an adverse event related to nasal swabbing, however none were assessed as serious. In the usability questionnaire, ≥95% of participants agreed or strongly agreed that the THFT was easy to use and they would feel confident using it at home. In addition, 88% of participants agreed or strongly agreed the nose swab was easy to do.

“The THFT should expand opportunities as an aid to rapid influenza detection and management beyond POC settings,” concluded researchers.

New research presented at the American Thoracic Society 2020 Virtual meeting showed the novel Theraflu Home FluTest demonstrated good sensitivity and specificity for influenza A and B viruses. 

ATS 2020: Novel At-home Rapid Influenza Diagnostic Test Demonstrates Good Sensitivity, Specificity

How many cases of coronavirus disease 2019 (COVID-19) have been confirmed in the US?

, as of today, August 11, 2020 at 9:35 AM, EDT, there have been:

The 5 states with the highest total confirmed cases are:

 with 32 781 reported fatalities, followed by 

 with 349 833 people who have recovered, followed by 

 California leads in number of persons tested

 with 8 998 353 people tested, followed by 

How many cases of COVID-19 have been confirmed globally?

recoveries.  
_________________________________________________________________________________

For more COVID-19 coverage for primary care, visit our

Global confirmed cases of COVID-19 have surpassed 20 million. We summarize more of today's global and US data from the Johns Hopkins COVID-19 interactive map.

COVID-19 Update: US and Global Cases, Deaths, and Recoveries as of August 11, 2020

US adolescents who use electronic cigarettes (e-cigarettes) are at a higher risk of lifetime asthma, and this association significantly increases when combined with marijuana use or cigarette smoking, according to a

E-cigarette use has been linked to asthma or asthma symptoms; however, little is known about the combined effect of e-cigarettes with marijuana or cigarette smoking. Therefore, researchers from the University of Pittsburgh and Children’s Hospital Pittsburgh examined whether e-cigarette use combined with marijuana or cigarette smoking could increase the risk for lifetime asthma among US adolescents.

The study included 21 532 adolescents aged 12-18 years (5222 with lifetime asthma and 16 310 control subjects) who participated in the 2015 and 2017 National Youth Risk Behavior Survey (YRBS). Researchers used the self-administered YRBS questionnaires to collect information on demographic characteristics, asthma, and use of an electronic vapor product, alone or in combination with marijuana and/or cigarette smoking.

For each product or substance, frequent use was defined as use for at least 10 days in the previous 30 days.

The results showed that frequent use of e-cigarettes, marijuana, and cigarette smoking were each significantly associated with 23%-68% increased odds of lifetime asthma. Also, frequent use of e-cigarettes was associated with 1.31 times increased odds of lifetime asthma (95% confidence interval, odds ratio=1.11-1.54).

Using e-cigarettes and marijuana (± cigarette smoking) was more strongly associated with lifetime asthma vs e-cigarette use alone.

Results were similar in analyses stratified by sex or race and ethnicity.

“Our results further support policies to stop use of e-cigarettes in children, as well as continued research on the detrimental effects of e-cigarettes on respiratory health,” concluded authors.

New research presented at the ATS 2020 Virtual meeting shows adolescents who use e-cigarettes along with marijuana and/or cigarette smoking have significantly higher odds of lifetime asthma.

Adolescents Who Use E-cigarettes, Marijuana Have Higher Odds of Lifetime Asthma

, as of today, August 10, 2020 at 8:46 AM, EDT, there have been:

 with 32 774 reported fatalities, followed by 

 with 344 845 people who have recovered, followed by 

 with 8 826 119 people tested, followed by 

US confirmed cases of COVID-19 surpassed 5 million; global recoveries have exceeded 12 million. We summarize more of today's data from the Johns Hopkins COVID-19 interactive map.

COVID-19 Update: US and Global Cases, Deaths, and Recoveries as of August 10, 2020

The COVID-19 pandemic has highlighted the critical role of vaccines, or in the case of SARS-CoV2, the lack of a vaccine.

Worrisomely, the rate of routine childhood vaccinations has decreased since mid-March this year. Specifically, 250 000 fewer doses of MMR were ordered from the Vaccine for Children program from mid-March to mid-April compared to the same time in 2019. There has been a similar drop in rates of other non-influenza vaccines. Fortunately, the US has only had 12 cases of measles in 7 locations during the first half of 2020. As you may remember, the US had a major outbreak in 2019 with 1282 cases in 31 states. Measles is not a benign disease. Ten percent of those 1282 cases required hospitalization. The US can't afford such a burden on the healthcare system. 

MMR Vaccination: How many doses does this patient need? 

Slideshows

MMR vaccination rates have significantly dropped since March. Do you know how many doses each of these 9 patients will need? 