Virani, Salim S.

Abstract Aim The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). Methods and results Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD −1.56; RR 0.94 (0.89–1.00)], cardiovascular mortality [ARD −1.49; RR 0.90 (0.81–1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. Conclusion This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Background: South Asians are at a significantly increased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), are diagnosed at relatively younger ages, and exhibit more severe disease phenotypes as compared with other ethnic groups. The pathophysiological mechanisms underlying T2D and CVD risk in South Asians are multifactorial and intricately related. Method: A narrative review of the pathophysiology of excess risk of T2D and CVD in South Asians. Result: T2D and CVD have shared risk factors that encompass biological factors (early life influences, impaired glucose metabolism, and adverse body composition) as well as behavioral and environmental risk factors (diet, sedentary behavior, tobacco use, and social determinants of health). Genetics and epigenetics also play a role in explaining the increased risk of T2D and CVD among South Asians. Additionally, South Asians harbor several lipid abnormalities including high concentration of small-dense low-density lipoprotein (LDL) particles, elevated triglycerides, low high-density lipoprotein (HDL)- cholesterol levels, dysfunctional HDL particles, and elevated lipoprotein(a) that predispose them to CVD. Conclusion: In this comprehensive review, we have discussed risk factors that provide insights into the pathophysiology of excess risk of T2D and CVD in South Asians.

Background Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients’ perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease ( CAD ) versus cerebrovascular disease (Ce VD ) versus both CAD and Ce VD ( CAD &Ce VD ). Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low‐density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133 US clinics. Among individuals with Ce VD only (n=403), CAD only (n=2202), and Ce VD & CAD (n=627), no significant differences were observed in patient‐perceived cardiovascular disease risk, beliefs on cholesterol lowering, or perceived effectiveness and safety of statin therapy. However, patients with Ce VD only were less likely to receive any statin therapy (76.2% versus 86.2%; adjusted odds ratio 0.64, 95% CI 0.45–0.91), or guideline‐recommended statin intensity (34.6% versus 50.4%; adjusted odds ratio 0.60, 95% CI 0.45–0.81) than those with CAD only. Individuals with Ce VD only were also less likely to achieve low‐density lipoprotein cholesterol <100 mg/ dL (59.2% versus 69.7%; adjusted odds ratio 0.79, 95% CI 0.64–0.99) than individuals with CAD alone. There were no significant differences in the use of any statin therapy or guideline‐recommended statin intensity between individuals with CAD &Ce VD and those with CAD only. Conclusions Despite lack of significant differences in patient‐perceived cardiovascular risk or statin beliefs, patients with Ce VD were significantly less likely to receive higher intensity statin or achieve low‐density lipoprotein cholesterol <100 mg/ dL than those with CAD only.

Background: Female patients have historically received less aggressive lipid management than male patients. Contemporary care patterns and the potential causes for these differences are unknown. Methods and Results: Examining the Patient and Provider Assessment of Lipid Management Registry—a nationwide registry of outpatients with or at risk for atherosclerotic cardiovascular disease—we compared the use of statin therapy, guideline-recommended statin dosing, and reasons for undertreatment. We specifically analyzed sex differences in statin treatment and guideline-recommended statin dosing using multivariable logistic regression. Among 5693 participants (43% women) eligible for 2013 American College of Cardiology/American Heart Association Cholesterol Guideline–recommended statin treatment, women were less likely than men to be prescribed any statin therapy (67.0% versus 78.4%; P <0.001) or to receive a statin at the guideline-recommended intensity (36.7% versus 45.2%; P <0.001). Women were more likely to report having previously never been offered statin therapy (18.6% versus 13.5%; P <0.001), declined statin therapy (3.6% versus 2.0%; P <0.001), or discontinued their statin (10.9% versus 6.1%; P <0.001). Women were also less likely than men to believe statins were safe (47.9% versus 55.2%; P <0.001) or effective (68.0% versus 73.2%; P <0.001) and more likely to report discontinuing their statin because of a side effect (7.9% versus 3.6%; P <0.001). Sex differences in both overall and guideline-recommended intensity statin use persisted after adjustment for demographics, socioeconomic factors, clinical characteristics, patient beliefs, and provider characteristics (adjusted odds ratio, 0.70; 95% CI, 0.61–0.81; P <0.001; and odds ratio, 0.82; 95% CI, 0.73–0.92; P <0.01, respectively). Sex differences were consistent across primary and secondary prevention indications for statin treatment. Conclusions: Women eligible for statin therapy were less likely than men to be treated with any statin or guideline-recommended statin intensity. A combination of women being offered statin therapy less frequently, while declining and discontinuing treatment more frequently, accounted for these sex differences in statin use.

OBJECTIVES Cardiac troponin T, measured using a high‐sensitive assay (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well‐designed prospective studies with extended follow‐up have been conducted. We aimed to estimate the association of hs‐cTnT and NT‐proBNP with 15‐year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study. DESIGN Prospective cohort study. SETTING Four US communities. PARTICIPANTS A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs‐cTnT and NT‐proBNP, respectively. MEASUREMENTS We examined association of hs‐cTnT and NT‐proBNP with 15‐year change (1996‐1998 to 2011‐2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs‐cTnT and NT‐proBNP into a three‐level categorical variable. RESULTS At baseline (1996‐1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs‐cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT‐proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (−.34; 95% confidence interval = −.63 to −.04). CONCLUSION Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future. J Am Geriatr Soc 67:2353–2361, 2019

Background Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient‐reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation. Methods and Results This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry. Patient surveys evaluated statin experience, reasons for declining or discontinuing statins, and beliefs about statins and cardiovascular disease risk. Overall, 1511 of 5693 adults (26.5%) were not on treatment. Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin. Conclusions More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered.

Background The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommended testing low‐density lipoprotein cholesterol ( LDL ‐C) to identify untreated patients with LDL ‐C ≥190 mg/dL, assess lipid‐lowering therapy adherence, and consider nonstatin therapy. We sought to determine whether clinician lipid testing practices were consistent with these guidelines. Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry enrolled primary and secondary prevention patients from 140 US cardiology, endocrinology, and primary care offices in 2015 and captured demographic data, lipid treatment history, and the highest LDL ‐C level in the past 2 years. Core laboratory lipid levels were drawn at enrollment. Among 7627 patients, 2787 (36.5%) had no LDL ‐C levels measured in the 2 years before enrollment. Patients without chart‐documented LDL ‐C levels were more often women, nonwhite, uninsured, and non–college graduates (all P <0.01). Patients without prior lipid testing were less likely to receive statin treatment (72.6% versus 76.0%; P =0.0034), a high‐intensity statin (21.5% versus 24.3%; P =0.016), nonstatin lipid‐lowering therapy (24.8% versus 27.3%; P =0.037), and had higher core laboratory LDL ‐C levels at enrollment (median 97 versus 92 mg/dL; P <0.0001) than patients with prior LDL ‐C testing. Of 166 individuals with core laboratory LDL ‐C levels ≥190 mg/dL, 36.1% had no LDL ‐C measurement in the prior 2 years, and 57.2% were not on a statin at the time of enrollment. Conclusions In routine clinical practice, LDL ‐C testing is associated with higher‐intensity lipid‐lowering treatment and lower achieved LDL ‐C levels.

Background Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. Methods and Results We compared statin use and dosing between adults >75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline‐recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were >75 years old. For primary prevention, use of any statin or high‐dose statin did not vary by age group: any statin, 62.6% in those >75 years old versus 63.1% in those ≤75 years old ( P =0.83); high‐dose statin, 10.2% versus 12.3% in the same groups ( P =0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [ P =0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66–1.01 [ P =0.06]), but were much less likely to receive a high‐intensity statin (23.5% versus 36.2% [ P <0.0001]; adjusted odds ratio, 0.54; 95% confidence interval, 0.45–0.65 [ P =0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P =0.003) or myalgias (27.3% versus 33.3%; P <0.001). Conclusions Overall use of statins was similar for primary prevention in those aged >75 years versus younger patients, yet older patients were less likely to receive high‐intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adults.