The 2018 ACC/AHA cholesterol guidelines: updates for family physicians

- Jennifer Middleton, MD, MPH

The American College of Cardiology (ACC) and American Heart Association (AHA), along with several other specialty organizations, have released a new "Guideline on the Management of Blood Cholesterol." Of note, this multi-specialty collaboration did not include primary care organizations like the American Academy of Family Physicians (AAFP) or the American College of Physicians (ACP); family physicians will find many similarities between this guideline and the 2013 ACC/AHA cholesterol guidelines, but a few changes may further complicate risk assessment and treatment discussions.

There is no change regarding the ACC/AHA's emphasis on lifestyle change as the basis for ASCVD prevention. There are also no changes to the treatment of two patient populations: individuals with clinical atherosclerotic cardiovascular disease (ASCVD) and individuals with serum low density lipoprotein cholesterol (LDL-C) levels greater than 190 mg/dL. For both groups, risk calculation with the ASCVD risk score is unnecessary; prescribe high-intensity (or maximally tolerated) statin therapy.

Recommendations regarding the use of statin medication for the primary prevention of ASCVD in persons with diabetes mellitus (DM) have been slightly revised. Moderate-intensity statin therapy is still recommended, as a starting point, for all patients with DM between the ages of 40-75 years. Previously, an ASCVD risk score greater than or equal to 7.5% was an indication for high-intensity statin therapy in this population; the 2018 guideline expands this recommendation to also include patients with one or more "diabetes-specific risk enhancers" (long duration of DM, albuminuria, eGFR < 60 mL/min, retinopathy, neuropathy, ankle-brachial index < 0.9) regardless of ASCVD risk score.

Perhaps the most complex changes center around those individuals aged 40-75 years who do not have DM and do not have clinical ASCVD. The 2013 guideline stratified these individuals into 2 risk categories, but the 2018 guideline now has 4:

• Low risk: ASCVD risk score < 5%
• Borderline risk: ASCVD score 5-7.4%
• Intermediate risk: ASCVD score 7.5-19.9%
• High risk: ASCVD score > 20%

Per this new guideline, low risk persons should focus on a healthy lifestyle. Borderline risk persons with one or more "risk enhancers" (see list below*) may consider moderate-intensity statin therapy after risks/benefits discussion with their physician. Intermediate risk persons should initiate moderate-intensity statin therapy if one or more risk enhancers* are present. High risk persons should initiate high-intensity statin therapy.

The 2018 ACC/AHA guideline also emphasizes following patients' LDL-C levels to both confirm adherence to therapy and to maximize benefit. They recommend that moderate-intensity statin therapy should lower LDL-C by 30-49%, and high-intensity statin therapy should lower LDL-C by at least 50%. The sources cited by the guideline to support these recommendations are expert opinion, however, and not randomized controlled trials (RCTs). It remains to be seen if primary care organizations such as the AAFP and ACP will endorse all or some of this guideline, especially this change regarding lipid monitoring.

The 2016 United States Preventive Services Task Force (USPSTF) recommendations regarding statins are similar regarding the benefit of primary prevention of those persons at highest risk (ASCVD risk score > 20%). The task force was less convinced regarding statins' primary prevention benefits among those at lower risk, giving a "B" grade for adults aged 40-75 years with an ASCVD risk score > or equal to 10% and at least one risk factor and a "C" grade for similarly aged adults with an ASCVD risk score between 7.5-9.9% and at least one risk factor. Statin therapy for primary prevention in persons > 75 years of age received an "I" grade, which is reasonably consistent with the 2018 ACC/AHA guideline's statement that "[f]or patients > 75 years of age, RCT evidence for statin therapy is not strong." The USPSTF also pointed out that most of the trials evaluating statins' efficacy in primary prevention enrolled participants based on the presence of risk factors, not based on the results of risk assessment tools.

The 2018 ACC/AHA cholesterol guideline contains much more content including a discussion regarding the use of statins in patients younger than 40 and also recommendations about appropriate candidates for coronary artery calcium scoring. The entire guideline has been published online ahead of print here. This "top 10 points" summary of the guideline may also be of interest. There's an AFP By Topic on Hyperlipidemia if you'd like to read more, which includes this Medicine by the Numbers article on "Statins in Persons at Low Risk of Cardiovascular Disease."

* ACC/AHA's ASCVD "risk enhancers" include: family history of premature ASCVD, persistently elevated LDL-C > 160 mg/dL, chronic kidney disease, metabolic syndrome, women with history of pre-eclampsia or premature menopause, history of inflammatory diseases (for example, rheumatoid arthritis, psoriasis, HIV), ethnicity, persistently elevated triglycerides > 175 mg/dL. 

Safe outpatient management of low-risk patients with acute pulmonary embolism

- Kenny Lin, MD, MPH

I've practiced family medicine long enough to remember when treatment of any patient with acute deep venous thrombosis (DVT) required hospitalization for several days administering intravenous unfractionated heparin and oral warfarin while waiting for the patient's international normalized ratio (INR) to reach a therapeutic level. Thanks to the development of low molecular-weight heparins and direct-acting oral anticoagulants (DOAC), outpatient treatment of uncomplicated DVT is now the norm. But patients with newly diagnosed pulmonary embolism (PE) are still typically hospitalized, since they often have hemodynamic instability or other potentially life-threatening conditions.

According to a 2017 article in American Family Physician, the American College of Chest Physicians suggests considering outpatient treatment of acute PE "if the risk of nonadherence is low and the patient is clinically stable; has no contraindications to anticoagulation, such as recent bleeding, severe renal or liver disease, or platelet count of less than 70; and feels capable of managing the disease at home." A recent Point-of-Care Guide reviewed clinical decision tools that predict mortality in patients with newly diagnosed PE. The simplified Pulmonary Embolism Severity Index (sPESI) stratifies patients into low and high risk categories. Low risk patients have a 30-day mortality rate of 1%, while high risk patients have a 9% mortality rate.

A prospective cohort study published in CHEST earlier this year enrolled 200 consecutive adults with newly diagnosed PE and a low risk of mortality using the related Pulmonary Embolism Severity Index (PESI). Participants were observed in the emergency department (ED) for 12 to 24 hours, then treated with anticoagulant medications in the outpatient setting (173 patients were treated with DOACs). After 90 days, no patients had died or suffered a recurrent venous thromboembolism (VTE). One patient had a major bleed after a traumatic thigh injury that required a blood transfusion and surgery.

A pragmatic controlled trial in Annals of Internal Medicine evaluated the effect of implementing an electronic clinical decision support system (CDSS) that included the PESI tool and an educational intervention on decision making for patients with acute PE in the 21 community EDs of Kaiser Permanente Northern California. 10 EDs received access to the CDSS and in-person education and feedback from an onsite emergency physician-researcher ("study champion"); the other 11 EDs served as control sites. The primary outcome was discharge to home from the ED or an ED-based outpatient observation unit. At the intervention sites, home discharge increased from 17.4% to 28%, while there were no changes in discharge practices at control sites. The intervention was not associated with increases in 30-day major adverse events (recurrent VTE, major hemorrhage, or all-cause mortality).

One day, one of my trainees will be able to write, "I've practiced family medicine long enough to remember when even low-risk patients with acute PE required hospitalization ..."

Putting the "family" in family physicians' care of children with type 2 diabetes

- Jennifer Middleton, MD, MPH

The current issue of AFP includes a review on Type 2 Diabetes Mellitus in Children, reviewing current guidelines for screening, diagnosis, and treatment. Children with type 2 diabetes mellitus (DM2) have optimal success with their treatment regimens when their families are engaged in their care. This engagement is crucial to success with both lifestyle and pharmacologic treatments.

Improving nutrition and exercise can lower A1Cs and improve clinical outcomes in children with DM2. Physicians can guide these changes by providing dietician referrals, exercise prescriptions, and screen time limits. Just as children and adolescents with DM2 tend to be obese, their families also tend to have similarly elevated body mass indices along with "high fat intake, minimal physical activity, and a high incidence of binge eating." Encouraging the entire family to work together to improve their nutrition and exercise improves the pediatric diabetic patient's chance of success with these changes. 

Sometimes, though, engaging children and families in the office alone is insufficient. Interdisciplinary interventions, such as multi-systemic therapy led by a trained family therapist, lowers A1Cs, reduces hospitalizations, and reduces costs in children with type 1 diabetes mellitus; though these interventions have not been systematically studied in children with DM2, it seems reasonable to assume that they would be similarly effective. Interestingly, parents often under-estimate their children's health-related quality of life; it may be that these interdisciplinary interventions help younger diabetic patients better understand the severity of their disease and, consequently, increase their adherence.

Unfortunately, children initially prescribed only lifestyle change after a DM2 diagnosis rarely succeed at sustained blood sugar improvement; lifestyle measures alone only effect meaningful change in hemoglobin A1C values in 10% of pediatric DM2 patients. As such, the American Academy of Pediatrics recommends that all children be started on metformin, in addition to lifestyle counseling, at the time of diagnosis. Pairing medication taking with daily family routines significantly increases medication adherence, as does multi-systemic therapy as outlined above. Encouraging parents to adopt a more permissive parenting style may be another technique to increase adherence to both lifestyle and medication recommendations; "[y]outh with T2DM who perceive more autonomy (less parental control) in day-to-day and diabetes tasks are more likely to adhere to medication regimens." 

Working collaboratively with families and other disciplines are strengths of our specialty and can greatly benefit our younger patients with DM2. You can read more about DM2 in the AFP By Topic on Diabetes: Type 2, which includes both further reading for physicians and patient resources.

For mild hypertension in low-risk adults, harms of drug therapy outweigh benefits

- Kenny Lin, MD, MPH

Prior to publication of the controversial 2017 ACC/AHA clinical practice guideline, stage 1 or "mild" hypertension was defined as a systolic blood pressure of 140-159 mm Hg and/or diastolic blood pressure of 90-99 mm Hg. Although guidelines have recommended that persons with mild hypertension receive anti-hypertensive drug therapy if lifestyle modification does not lower blood pressure below 140/90, a Cochrane review found that such therapy did not reduce cardiovascular disease (CVD) events, stroke, or mortality compared to placebo. A 2015 meta-analysis that included high-risk persons (patients with diabetes and/or who had received prior antihypertensive treatment) suggested that drug therapy for mild hypertension may prevent CVD events, but others have argued that this analysis mixed apples with oranges and did not establish benefits for adults at low CVD risk.

A retrospective cohort study recently published in JAMA Internal Medicine sought to clarify the benefits and harms of drug therapy in low-risk adults with mild hypertension using data from 40,000 patients in an electronic health records database in the United Kingdom. The authors compared the outcomes of persons aged 18 to 74 with mild hypertension who were prescribed anti-hypertensive medications within 12 months of diagnosis to those in similar untreated persons. Persons with a history of CVD, left ventricular hypertrophy, atrial fibrillation, diabetes, chronic kidney disease, or a family history of premature heart disease were excluded from the study.

After a median follow-up duration of 5.8 years, there were no differences between the groups in all-cause mortality, stroke, myocardial infarction, acute coronary syndrome, or heart failure. However, the treated group had an increased risk of hypotension (number needed to harm = 41 at 10 years), syncope (NNH = 35), electrolyte abnormalities (NNH = 111), and acute kidney injury (NNH = 91).

Although ideally the findings from this observational study should be confirmed in a randomized, controlled trial, it is unlikely that a trial will ever be performed due to the large number of participants that would be needed in order to provide enough statistical power to detect a difference in mortality or rare CVD events in this population. In the meantime, the best available evidence suggests that the harms of drug therapy outweigh benefits for low-risk adults with a systolic blood pressure of 140-159 mm Hg and/or diastolic blood pressure of 90-99 mm Hg (recently redefined by the ACC/AHA as stage 2 hypertension). In these patients, family physicians and other primary care clinicians should emphasize nonpharmacologic management strategies such as a diet with a high intake of vegetables, fruits, and whole grains; moderating excessive sodium intake and alcohol consumption; and at least 150 minutes per week of moderate-intensity aerobic physical activity.

Acute Flaccid Myelitis: what family physicians should know

- Jennifer Middleton, MD, MPH

Although still quite rare, occurrences of acute flaccid myelitis (AFM), a polio-like condition that results in sudden limb weakness, have been increasing in the United States (US). Most of the affected individuals are children, and a definitive cause is not yet known. Family physicians can aid the Centers for Disease Control and Prevention (CDC)'s investigation by recognizing AFM's presentation and reporting suspected cases to their local health departments.

AFM is not a new condition, but its prevalence in the United States has been increasing, with 386 confirmed cases across 34 states since August of 2014. AFM's prevalence has been higher in the summer months during this time, but cases have been reported year-round. Patients present with sudden loss of strength in one or more limbs, with associated loss of muscle tone and reflexes. Some patients may also have facial drooping or speech changes. Urinary retention has occasionally been noted, and, rarely, some patients even experience respiratory failure. MRI of the spine reveals a gray matter lesion, and cerebrospinal fluid (CSF) typically shows excess white blood cells.

Often, a viral syndrome precedes these neurologic symptoms, but CDC researchers have yet to identify a clear etiology, viral or otherwise. Testing of affected individuals for poliovirus has consistently been negative. The increase in AFM cases does coincide with increased enterovirus D68 activity in the US, but testing in AFM patients has been inconsistent re: accompanying enterovirus infection. With no clearly identified cause, the CDC advises general prevention strategies such as hand washing and mosquito bite avoidance. Treatment for AFM is supportive, with the involvement of neurologists, physical therapists, and occupational therapists.

Physicians should promptly report any patient who presents with sudden flaccid limb weakness, regardless of lab or imaging findings; gathering information from affected individuals will be critical to identifying AFM's etiology. Family physicians can report cases by contacting their local health department and completing this patient summary form, available on the CDC website. For patients with muscle weakness that don't fit the clinical picture of AFM, this AFP article on "Evaluation of the Patient with Muscle Weakness" may be helpful. Since West Nile virus can also cause AFM, this 2016 AFP article on "Emerging Vector-Borne Diseases" may also be of interest.

PSA screening: USPSTF recommendations changed, but the evidence did not

- Kenny Lin, MD, MPH

Comparing the 2018 U.S. Preventive Services Task Force (USPSTF) recommendation statement on prostate cancer screening in the October 15th issue of AFP with its previous recommendation, the first question family physicians ought to ask is: what new evidence compelled the USPSTF to move from recommending against PSA screening in all men to determining that there was a small net benefit for screening in some men? Did another major randomized trial show a reduction in all-cause or prostate cancer-specific mortality in men invited to screening? Did other systematic reviewers re-analyze the evidence and find a mortality benefit where none previously existed? Have urologists or radiation oncologists developed new treatments for localized prostate cancer that no longer cause erectile dysfunction, urinary incontinence, or infections?

No, no, and no.

One of the Top 20 Research Studies of 2017 for Primary Care Physicians, the only U.S. trial of PSA-based screening for prostate cancer, reported that after a median followup of 15 years, there were still no differences in mortality between the two groups. In 2018, a large U.K. randomized trial of a single PSA screening also reported no effect on prostate cancer mortality after a median followup of 10 years. In both trials, more prostate cancers were diagnosed in the groups assigned to routine screening, but treating these cancers did not lead to improved health outcomes.

Last month, the authors of a 2010 Cochrane review of PSA screening (previously summarized in AFP's Cochrane for Clinicians) published an updated meta-analysis in the BMJ that incorporated the U.K. trial findings and extended followup of the U.S. and European screening trials and concluded that "at best, screening for prostate cancer leads to a small reduction in disease-specific mortality over 10 years but does not affect overall mortality." They also estimated that "for every 1000 men screened, approximately 1, 3, and 25 more men would be hospitalized for sepsis, require pads for urinary incontinence, and report erectile dysfunction, respectively." Another U.K. trial comparing active surveillance for localized prostate cancer with immediate surgery or radiation therapy found higher rates of clinical progression in the active surveillance group, but no differences in health-related quality of life or mortality.

Representing the views of American Academy of Family Physicians (AAFP), Drs. James Stevermer and Kenneth Fink explained in an editorial why "the AAFP believes that the net benefit [of PSA screening] does not justify routine screening or routinely offering shared decision making." The AAFP took the unusual step of declining to endorse the USPSTF recommendation statement and instead writing its own clinical preventive services recommendation that emphasizes the harms of routine screening. Men who bring up the topic of PSA screening should engage in shared decision-making with their physicians about the benefits and harms of screening and express a clear preference to be screened before undergoing the test.