Yashashwi Pokharel

Treatment Gaps in Adults with Heterozygous Familial Hypercholesterolemia in the United States: Data from the CASCADE-FH Registry

Background— Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. Methods and Results— We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08–2.82) and hypertension (2.48; 1.92–3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86–28.86) and use of >1 LDL-lowering medication (1.80; 1.34–2.41). Conclusions— FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.

Personalizing the Intensity of Blood Pressure Control: Modeling the Heterogeneity of Risks and Benefits From SPRINT (Systolic Blood Pressure Intervention Trial)

Background— In SPRINT (Systolic Blood Pressure Intervention Trial), patients with hypertension and high cardiovascular risk treated with intensive blood pressure (BP) control (<120 mm Hg) had fewer major adverse cardiovascular events (MACE) and deaths but higher rates of treatment-related serious adverse events (SAE) than patients randomized to standard BP control (<140 mm Hg). However, the degree of benefit or harm for an individual patient could vary because of heterogeneity in treatment effect. Methods and Results— Using patient-level data from 9361 randomized patients in SPRINT, we developed models to predict risk for MACE or death and treatment-related SAE to allow for individualized BP treatment goals based on each patient’s projected risk and benefit of intensive versus standard BP control. Models were internally validated using bootstrap resampling and externally validated on 4741 patients from the ACCORD-BP (The Action to Control Cardiovascular Risk in Diabetes blood pressure) trial. Among 9361 SPRINT patients, 755 patients (8.1%) had a MACE or death event and 338 patients (3.6%) had a treatment-related SAE during a median follow-up of 3.3 years. The MACE/death and the SAE model had C statistics of 0.72 and 0.70, respectively, in the derivation cohort and 0.69 and 0.65 in ACCORD. The MACE/death model had 10 variables including treatment interactions with age, baseline systolic BP, and diastolic BP, and the SAE model had 8 variables including treatment interaction with number of BP medications. Intensive BP treatment was associated with a mean 2.2±2.6% lower risk of MACE/death compared with standard treatment (range, 20.7% lower risk to 19.6% greater risk among individual patients) and a mean 2.2±1.2% higher risk for SAEs (range, 0.5%–15.8% more harm in individual patients). Conclusions— To translate the findings from SPRINT to clinical practice, we developed prediction models to tailor the intensity of BP control based on the projected risk and benefit for each unique patient. This approach should be prospectively tested to better engage patients in shared medical decision making and to improve outcomes. Clinical Trial Registration— URL: https://clinicaltrials.gov. Unique identifier: NCT01206062.

Neck Circumference Is Not Associated With Subclinical Atherosclerosis in Retired National Football League Players

Neck circumference (NC) is associated with metabolic syndrome (MetS) in the general population. It is not known if NC is associated with MetS and subclinical atherosclerosis in retired National Football League (NFL) players.

High-Sensitivity Troponin T and Cardiovascular Events in Systolic Blood Pressure Categories Atherosclerosis Risk in Communities Study

Based on observational studies, there is a linear increase in cardiovascular risk with higher systolic blood pressure (SBP), yet clinical trials have not shown benefit across all SBP categories. We assessed whether troponin T measured using high-sensitivity assay was associated with cardiovascular disease within SBP categories in 11 191 Atherosclerosis Risk in Communities study participants. Rested sitting SBP by 10-mm Hg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease, and stroke were ascertained for a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with SBP<140 mm Hg and troponin T ≥3 ng/L. Higher troponin T was associated with increasing cardiovascular events across most SBP categories. The association was strongest for heart failure and least strong for stroke. There was no similar association of SBP with cardiovascular events across troponin T categories. Individuals with troponin T ≥3 ng/L and SBP <140 mm Hg had higher cardiovascular risk compared with those with troponin T <3 ng/L and SBP 140 to 159 mm Hg. Higher troponin T levels within narrow SBP categories portend increased cardiovascular risk, particularly for heart failure. Individuals with lower SBP but measurable troponin T had greater cardiovascular risk compared with those with suboptimal SBP but undetectable troponin T. Future trials of systolic hypertension may benefit by using high-sensitivity troponin T to target high-risk patients.

Cardiovascular Disease Performance Measures in the Outpatient Setting in India: Insights From the American College of Cardiology's PINNACLE India Quality Improvement Program (PIQIP)

Background India has a growing burden of cardiovascular disease (CVD), yet data on the quality of outpatient care for patients with coronary artery disease, heart failure, and atrial fibrillation in India are very limited. We collected data on performance measures for 68 196 unique patients from 10 Indian cardiology outpatient departments from January 1, 2011, to February 5, 2014, in the American College of Cardiology’s PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP). PIQIP is India’s first national outpatient CVD quality-improvement program. Methods and Results In the PIQIP registry, we estimated the prevalence of CVD risk factors (hypertension, diabetes, dyslipidemia, and current tobacco use) and CVD among outpatients. We examined adherence with performance measures established by the American College of Cardiology, the American Heart Association, and the American Medical Association Physician Consortium for Performance Improvement for coronary artery disease, heart failure, and atrial fibrillation. There were a total of 68 196 patients (155 953 patient encounters), with a mean age of 50.6 years (SD 18.2 years). Hypertension was present in 29.7% of patients, followed by diabetes (14.9%), current tobacco use (7.6%), and dyslipidemia (6.5%). Coronary artery disease was present in 14.8%, heart failure was noted in 4.0%, and atrial fibrillation was present in 0.5% of patients. Among eligible patients, the reported use of medications was as follows: aspirin in 48.6%, clopidogrel in 37.1%, and statin-based lipid-lowering therapy in 50.6% of patients with coronary artery disease; RAAS (renin–angiotensin–aldosterone system) antagonist in 61.9% and beta-blockers in 58.1% of patients with heart failure; and oral anticoagulants in 37.0% of patients with atrial fibrillation. Conclusions This pilot study, initiated to improve outpatient CVD care in India, presents our preliminary results and barriers to data collection and demonstrates that such an initiative is feasible in a resource-limited environment. In addition, we attempted to outline areas for further improvement in outpatient CVD care delivery in India.

Association between high-sensitivity troponin T and cardiovascular risk in individuals with and without metabolic syndrome: The ARIC study

Background Metabolic syndrome (MetS) is associated with increased risk for cardiovascular disease, but there is heterogeneity in this risk. We evaluated whether high-sensitivity troponin T (hs-cTnT), a marker associated with cardiovascular disease, can stratify risk in MetS. Methods We evaluated associations between MetS (and groups with similar number of MetS components) and incident heart failure hospitalization, coronary heart disease, stroke and death using hs-cTnT categories after adjusting for risk factors/markers between 1996 and 2011 in 8204 individuals in the Atherosclerosis Risk In Communities study. Results The mean age of the population was 63 years (56% women, 19% Blacks). hs-cTnT levels were higher with MetS and with increasing MetS components. In individuals with MetS, higher hs-cTnT levels were associated with increased hazard ratios for heart failure, coronary heart disease and death. Within each number of MetS components, higher hs-cTnT was associated with progressively higher heart failure, coronary heart disease and death hazards. The association was particularly strong for heart failure. With increasing hs-cTnT categories, the hazard ratios (95% confidence interval) for heart failure in individuals with MetS increased gradually from 1.68 (1.31–2.16) to 3.76 (2.69–5.26) (p-trend < 0.001) compared with those with MetS and hs-cTnT < 5 ng/l; and respective hazard ratios with increasing hs-cTnT categories in those with all five MetS components ranged from 2.22 (1.17–4.21) to 4.23 (1.89–9.50) (p-trend 0.004) compared with those with all five MetS components and hs-cTnT < 5 ng/l. However, mostly there were no significant interactions of hs-cTnT with MetS or its components. Conclusion hs-cTnT is useful for identifying MetS patients with increased hazards for coronary heart disease, death and particularly heart failure.

Practice-Level Variation in Statin Use Among Patients With Diabetes: Insights From the PINNACLE Registry

Statins reduce cardiovascular disease (CVD) and mortality risk in patients with diabetes [(1)][1]. Practice-level variation in statin use among diabetic patients in cardiology practices is unknown. Accordingly, we examined practice-level variation in statin therapy among 40- to 75-year-old patients

Guideline‐Directed Medication Use in Patients With Heart Failure With Reduced Ejection Fraction in India: American College of Cardiology's PINNACLE India Quality Improvement Program

Little is known about the use of guideline‐directed medical therapy (GDMT) in outpatients with heart failure with reduced left ventricular ejection fraction (HFrEF; ≤40%) in India. Our objective was to understand the use of GDMT in outpatients with HFrEF in India. The Practice Innovation And Clinical Excellence (PINNACLE) India Quality Improvement Program (PIQIP) is a registry for cardiovascular quality improvement in India supported by the American College of Cardiology Foundation. Between January 2008 and September 2014, we evaluated documentation of use of angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and β‐blockers, or both, among outpatients with HFrEF seeking care in 10 centers enrolled in the PIQIP registry. Among 75 639 patients in the PIQIP registry, 34 995 had EF reported, and 15 870 had an EF ≤40%. The mean age was 56 years; 23% were female. Hypertension, diabetes, coronary artery disease, and myocardial infarction were present in 37%, 23%, 27%, and 17%, respectively. Use of ACEIs/ARBs, β‐blockers, and both were documented in 33.5%, 34.9%, and 29.6% of patients, respectively. The documentation of GDMT was higher in men, in patients age ≥65 years, and in those with presence of hypertension, diabetes, or coronary artery disease. Documentation of GDMT gradually increased over the study period. Among patients enrolled in the PIQIP registry, about two‐thirds of patients with EF ≤40% did not have documented receipt of GDMT. This study is an initial step toward improving adherence to GDMT in India and highlights the feasibility of examining quality of care in HFrEF in a resource‐limited setting.

Genetic Testing in Hyperlipidemia

Hereditary dyslipidemias are often underdiagnosed and undertreated, yet with significant health implications, most importantly causing preventable premature cardiovascular diseases. The commonly used clinical criteria to diagnose hereditary lipid disorders are specific but are not very sensitive. Genetic testing may be of value in making accurate diagnosis and improving cascade screening of family members, and potentially, in risk assessment and choice of therapy. This review focuses on using genetic testing in the clinical setting for lipid disorders, particularly familial hypercholesterolemia.

Association of midlife lipids with 20-year cognitive change: A cohort study

Existing studies predominantly consider the association of late‐life lipid levels and subsequent cognitive change. However, midlife rather than late‐life risk factors are often most relevant to cognitive health.