Familial hypercholesterolemia (FH) is a genetic disease characterized by substantial elevations of low-density lipoprotein cholesterol, unrelated to diet or lifestyle. Untreated FH patients have 20 times the risk of developing coronary artery disease, compared with the general population. Estimates indicate that as many as 1 in 500 people of all ethnicities and 1 in 250 people of Northern European descent may have FH; nevertheless, the condition remains largely undiagnosed. In the United States alone, perhaps as little as 1% of FH patients have been diagnosed. Consequently, there are potentially millions of children and adults worldwide who are unaware that they have a life-threatening condition. In countries like the Netherlands, the United Kingdom, and Spain, cascade screening programs have led to dramatic improvements in FH case identification. Given that there are currently no systematic approaches in the United States to identify FH patients or affected relatives, the patient-centric nonprofit FH Foundation convened a national FH Summit in 2013, where participants issued a "call to action" to health care providers, professional organizations, public health programs, patient advocacy groups, and FH experts, in order to bring greater attention to this potentially deadly, but (with proper diagnosis) eminently treatable, condition.

Successful implementation of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines hinges on a clear understanding of the clinician-patient risk discussion (CPRD). This is a dialogue between the clinician and patient about potential for atherosclerotic cardiovascular disease risk reduction benefits, adverse effects, drug-drug interactions, and patient preferences. Designed especially for primary prevention patients, this process of shared decision making establishes the appropriateness of a statin for a specific patient. CPRD respects the autonomy of an individual striving to make an informedchoice aligned with personal values and preferences. Dedicating sufficient timeto high-quality CPRD offers an opportunity to strengthen clinician-patient relationships, patient engagement, and medication adherence. We review the guideline-recommended CPRD, the general concept of shared decision making and decision aids, the American College of Cardiology/American Heart Association Risk Estimator application as an implementation tool, and address potential barriers to implementation.

BACKGROUND—: Free radical scavengers have failed to improve patient outcomes promoting the concept that clinically important oxidative stress (OS) may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of non-free radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS—: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (p<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (=+1 SD & <-1 SD respectively) were associated with higher mortality (adjusted HR 1.63 (95% CI 1.19-2.21; HR 2.19 (95% CI 1.50-3.19), respectively) compared to those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR 1.92 (95% CI 1.39-2.64) and was independent of and additive to hs-CRP level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS—: A high burden of OS, quantified by the plasma aminothiols, cystine, glutathione and their ratio is associated with mortality in patients with CAD, a finding that is independent of and additive to the inflammatory burden. Importantly, this data supports the emerging role of non-free radical biology in driving clinically important oxidative stress.

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice. It constitutes a major public health problem, with total related annual expenses estimated at $6.65 billion. The American Heart Association developed Life's Simple 7 (LS7) to define and monitor ideal cardiovascular health (CVH). In this review, we examine the role of individual components of LS7 to provide further insight regarding potential influence of achieving AHA's strategic goal on AF prevention. While significant advances have been made in the secondary prevention of AF, little progress has been made to prevent the first occurrence of this arrhythmia in at-risk patients. Improvement of overall cardiovascular health as defined by LS7 may substantially reduce AF risk.

Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment.

Background and aims Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation associated with atherosclerosis. Whether suPAR levels are associated with prevalent peripheral arterial disease (PAD) and its adverse outcomes remains unknown and is the aim of the study. Methods SuPAR levels were measured in 5810 patients (mean age 63 years, 63% male, 77% with obstructive coronary artery disease [CAD]) undergoing cardiac catheterization. The presence of PAD (n = 967, 17%) was classified as carotid (36%), lower/upper extremities (30%), aortic (15%) and multisite disease (19%). Multivariable logistic and Cox regression models were used to determine independent predictors of prevalent PAD and outcomes including all-cause death, cardiovascular death and PAD-related events after adjustment for age, gender, race, body mass index, smoking, diabetes, hypertension, hyperlipidemia, renal function, heart failure history, and obstructive CAD. Results Plasma suPAR levels were 22.5% (p < 0.001) higher in patients with PAD compared to those without PAD. Plasma suPAR was higher in patients with more extensive PAD (≥2 compared to single site) p < 0.001. After multivariable adjustment, suPAR was associated with prevalent PAD; odds ratio (OR) for highest compared to lowest tertile of 2.0, 95% CI (1.6–2.5) p < 0.001. In Cox survival analyses adjusted for clinical characteristics and medication regimen, suPAR (in the highest vs. lowest tertile) remained an independent predictor of all-cause death [HR 3.1, 95% CI (1.9–5.3)], cardiovascular death [HR 3.5, 95% CI (1.8–7.0)] and PAD-related events [HR = 1.8, 95% CI (1.3–2.6) p < 0.001 for all]. Conclusions Plasma suPAR level is predictive of prevalent PAD and of incident cardiovascular and PAD-related events. Whether SuPAR measurement can help screen, risk stratify, or monitor therapeutic responses in PAD requires further investigation.

Background-Food deserts (FD), neighborhoods defined as low-income areas with low access to healthy food, are a public health concern. We evaluated the impact of living in FD on cardiovascular risk factors and subclinical cardiovascular disease (CVD) with the hypothesis that people living in FD will have an unfavorable CVD risk profile. We further assessed whether the impact of FD on these measures is driven by area income, individual household income, or area access to healthy food. Methods and Results-We studied 1421 subjects residing in the Atlanta metropolitan area who participated in the METAHealth study (Morehouse and Emory Team up to Eliminate Health Disparities; n=712) and the Predictive Health study (n=709). Participants' zip codes were entered into the United States Food Access Research Atlas for FD status. Demographic data, metabolic profiles, hs-CRP (high-sensitivity C-reactive protein) levels, oxidative stress markers (glutathione and cystine), and arterial stiffness were evaluated. Mean age was 49.4 years, 38.5% male and 36.6% black. Compared with those not living in FD, subjects living in FD (n=187, 13.2%) had a higher prevalence of hypertension and smoking, higher body mass index, fasting glucose, and 10-year risk for CVD. They also had higher hs-CRP (P=0.014), higher central augmentation index (P=0.015), and lower glutathione level (P=0.003), indicative of increased oxidative stress. Area income and individual income, rather than food access, were associated with CVD risk measures. In a multivariate analysis that included food access, area income and individual income, both low-income area and low individual household income, were independent predictors of a higher 10-year risk for CVD. Only low individual income was an independent predictor of higher hs-CRP and augmentation index. Conclusions-Although living in FD is associated with a higher burden of cardiovascular risk factors and preclinical indices of CVD, these associations are mainly driven by area income and individual income rather than access to healthy food.

The 1245.29 Trial recently showed that empaglifozin improved both blood pressure and glucose control in African American (AA) patients with type 2 diabetes (T2D) and hypertension. Using the Diabetes Collaborative Registry, a large-scale US registry of outpatients with diabetes recruited from primary care, cardiology and endocrinology practices, we sought to understand the potential impact of these observations in routine clinical practice. Among 74 290 AA patients with T2D from 368 US clinics, 60.4% had hypertension, of whom 34.5% had systolic blood pressure ≥ 140 mm Hg (20.8% of the total AA T2D population). Only 1.7% of this eligible population had been prescribed a sodium-glucose co-transporter two inhibitor. The mean estimated 5-year risk of cardiovascular death was 7.7%, which could be reduced to 6.2% when modelling the antihypertensive effect of empagliflozin across the eligible population (based on an 8-mm Hg blood pressure reduction). These findings may represent a potential opportunity for better management of cardiovascular risk factors and improved outcomes in this vulnerable cohort.

Background: Although practice guidelines stress individualization of glucose management in patients with type 2 diabetes (T2D), the extent to which providers take patient factors into account when selecting medications is not well known. Methods: Diabetes Collaborative Registry (DCR) is an outpatient diabetes registry including primary care, cardiology, and endocrinology practices. T2D medications were grouped as those which may be suboptimal for key patient subgroups, and we examined patient factors associated with use of these agents using hierarchical, multivariable Poisson models. Results: In DCR, 157,551 patients from 374 US practices were prescribed a glucose-lowering medication. Patients with morbid obesity were more likely treated with medications prone to cause weight gain (relative rate [RR] 1.09, 95% CI 1.07–1.11). Older patients were more likely to be treated with medications with increased risk of hypoglycemia (RR 1.04 per 5 years, 95% CI 1.04–1.05). Patients with CKD 4/5 were less likely to be treated with agents with known risk in patients with advanced CKD (RR 0.74, 95% CI 0.71–0.77). Patients with coronary artery disease were no more or less likely to be treated with medications with potential cardiovascular safety issues (RR 0.99, 95% CI 0.96–1.01). Conclusions: We observed some targeted use of glucose-lowering therapies in certain subgroups but also identified potential opportunities for better personalization of treatment. Data sources such as the DCR can highlight potential areas for improving targeted approaches to pharmacologic therapy in order to optimize selection of patients most likely to benefit (and least likely to be harmed) from treatments.

Background: Low diastolic blood pressure (DBP) is associated with increased risk of cardiovascular events. In patients with coronary artery disease (CAD), limitations in coronary blood flow and immune activity are implicated mechanisms, but evidence is lacking. We investigated the association between DBP, biomarkers of myocardial injury, inflammation, immune activation and incident events in patients with CAD. Methods: We studied 2448 adults (mean age 65 ± 12 years, 68% male, median follow-up 4.5 years) with CAD. DBP was categorized into 10 mm Hg increments. Biomarkers of myocardial injury (high sensitivity cardiac troponin-I [hs-cTnI]) and immune activity/inflammation (soluble urokinase plasminogen activator receptor [suPAR]) were dichotomized at their median values. DBP 70–79 mm Hg was used as the referent group, and individuals were followed prospectively for adverse outcomes. Results: After adjusting for demographic and clinical covariates, individuals with DBP < 60 mm Hg had increased odds of elevated levels of hs-cTnI (OR = 1.68; 95% CI = 1.07, 2.65) and suPAR (OR = 1.71; 95% CI = 1.10, 2.65) compared to the referent group. Additionally, DBP < 60 mm Hg was associated with increased adjusted risk of cardiovascular death or MI (HR = 2.04; 95% CI = 1.32, 3.16) and all-cause mortality (HR = 2.41; 95% CI = 1.69, 3.45). Conclusion: In patients with CAD, DBP < 60 mm Hg is associated with subclinical myocardial injury, immune/inflammatory dysregulation and incident events. Aggressive BP control may be harmful in these patients, and further investigation is warranted to determine appropriate BP targets in patients with CAD.