Circulating ketone bodies and cardiovascular outcomes: the MESA study.

AIMS: Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). METHODS AND RESULTS: This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12-2.12) and 1.37 (1.04-1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17-2.97) increased rate of CVD mortality and an 81% (1.45-2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07-2.65), per 10-fold increase in total KB]. CONCLUSION: The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.

Understanding the molecular mechanisms of statin pleiotropic effects.

Statins represent the cornerstone of pharmacotherapy for the prevention of atherosclerotic cardiovascular disease. These medications not only reduce low-density lipoprotein cholesterol (LDL-C) via inhibition of 3-hydroxy-3-methylglutarate attached to CoA reductase, the key rate-limiting step in the cholesterol biosynthetic pathway, but also upregulate expression of the low-density lipoprotein receptor, improving serum clearance. Given LDL-C is a causal risk factor for the development of atherosclerosis, these complementary mechanisms largely explain why statin therapy leads to reductions in major adverse cardiovascular events. However, decades of basic and clinical research have suggested that statins may exert other effects independent of LDL-C lowering, termed pleiotropic effects, which have become a topic of debate among the scientific community. While some literature suggests statins may improve plaque stability, reduce inflammation and thrombosis, decrease oxidative stress, and improve endothelial function and vascular tone, other studies have suggested potential harmful pleiotropic effects related to increased risk of muscle-related side effects, diabetes, hemorrhagic stroke, and cognitive decline. Furthermore, the introduction of newer, non-statin LDL-C lowering therapies, including ezetimibe, proprotein convertase subtilisin/Kexin Type 9, and bempedoic acid, have challenged the statin pleiotropy theory. This review aims to provide a historical background on the development of statins, explore the mechanistic underpinnings of statin pleiotropy, review the available literature, and provide up to date examples that suggest statins may exert effects outside of LDL-C lowering and the cardiovascular system.

Association of silent myocardial infarction on electrocardiogram and coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. OBJECTIVE: Characterize the relationship between SMI on ECG and CAC. METHODS: Eligible participants from the Multi-Ethnic Study of Atherosclerosis study had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. RESULTS: Among 6705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0-261.7] vs. 0 [0-81.5]; p < .0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48-3.20, p < .0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06-2.16, p = .02). CONCLUSION: An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.

Specialty preference for cardiovascular prevention practice in the Southeast US and role of a preventive cardiologist.

INTRODUCTION: Cardiovascular disease (CVD) prevention is practiced concurrently by providers from several specialties. Our goal was to understand providers' preference of specialties in CVD prevention practice and the role of preventive cardiologists. MATERIALS AND METHODS: Between 11 October 2021 and 1 March 2022, we surveyed providers from internal medicine, family medicine, endocrinology, and cardiology specialties to examine their preference of specialties in managing various domains of CVD prevention. We examined categorical variables using Chi square test and continuous variables using t or analysis of variance test. RESULTS: Of 956 invitees, 263 from 21 health systems and 9 states responded. Majority of respondents were women (54.5%), practicing physicians (72.5%), specializing in cardiology (43.6%), and working at academic centers (51.3%). Respondents favored all specialties to prescribe statins (43.2%), ezetimibe (37.8%), sodium-glucose cotransporter-2 (SGLT2) inhibitors (30.5%), and aspirin in primary prevention (36.3%). Only 7.9% and 9.5% selected cardiologists and preventive cardiologists, respectively, to prescribe SGLT2 inhibitors. Most preferred specialists (i.e. cardiology and endocrinology) to manage advanced lipid disorders, refractory hypertension, and premature coronary heart disease. The most common conditions selected for preventive cardiologists to manage were genetic lipid disorders (17%), cardiovascular risk assessment (15%), dyslipidemia (13%), and refractory/resistant hypertension (12%). CONCLUSIONS: For CVD prevention practice, providers favored all specialties to manage common conditions, specialists to manage complex conditions, and preventive cardiologists to manage advanced lipid disorders. Cardiologists were least preferred to prescribe SGLT2 inhibitor. Future research should explore reasons for selected CVD prevention practice preferences to optimize care coordination and for effective use of limited expertise.

Should a Statin be Given to All Hypertensive Patients?

PURPOSE OF REVIEW: To review the milestone trials and recent literature supporting statin therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) and to provide rationale for more generalized use of statin therapy among patients treated for hypertension. RECENT FINDINGS: Hypertension is a leading modifiable risk factor for ASCVD worldwide. Randomized controlled trial evidence supports initiation of antihypertensive medication for stage 2 hypertension regardless of ASCVD risk. The HOPE-3 trial tested statin therapy in intermediate-risk individuals (defined as an annual risk of major cardiovascular events of approximately 1%) for primary prevention of ASCVD and reported significant reductions in cardiovascular events in all statin treatment arms, with the greatest benefit observed in patients in the highest tertile of systolic blood pressure. Based on the current data, patients with stage 2 hypertension with an indication for antihypertensive therapy may benefit from the addition of statin therapy in the primary prevention setting. Patients with hypertension have an elevated risk for ASCVD that appears to be modifiable beyond implementation of antihypertensive therapy. The addition of statin therapy in patients treated with antihypertensive therapy may further help to lower risk of future cardiovascular events.

Polygenic Risk Scores to Identify CVD Risk and Tailor Therapy: Hope or Hype?

PURPOSE OF REVIEW: The purpose of this review is to understand the conceptual basis and implications of polygenic risk scores (PRS) in assessing risk of future coronary artery disease (CAD). RECENT FINDINGS: Genetic information from the USA and beyond has been pooled together to create population-based biobanks, composed of millions of genotyped individuals, which have helped further our understanding of the relationship between single nucleotide polymorphisms (SNPs) and CAD. Contemporary PRS composed of millions of SNPs now serve as the gold standard and have been evaluated in several cohort studies to predict risk of CAD and potentially help guide pharmacotherapy. The development of PRS has enhanced our understanding of the relationship between genes and disease, thereby facilitating CAD risk prediction. While certain constraints currently limit their utility in clinical practice, further refinement of this tool will enable clinicians to more fully understand genetic risk and improve preventive care.

The utility of silent myocardial infarction on electrocardiogram as an ASCVD risk enhancer for primary prevention: The multi-ethnic study of atherosclerosis.

BACKGROUND: The 2018 AHA/ACC cholesterol guidelines introduced a new list of markers called "risk enhancers" that, if present, confer an increased risk of atherosclerotic cardiovascular disease (ASCVD). Silent myocardial infarction (SMI) on electrocardiogram (ECG) is notably absent, even though it associated with future ASCVD. METHODS: We assessed the utility of SMI on ECG as a risk-enhancer in intermediate-risk participants in MESA (Multi-Ethnic Study of Atherosclerosis) - those with 10-year ASCVD risk of 5-20% by the pooled cohort equation (PCE). SMI was defined as major Q-wave abnormality or minor Q/QS waves in the setting of major ST-T abnormalities without prevalent clinical cardiovascular disease. RESULTS: Among 2946 participants (mean age 63.1 ± 7.6, 53.9% women, 36% white, 11% Chinese-American, 33% African-American, 19% Hispanic), 66 (2.2%) had SMI at baseline. After a median 15.8 years of follow-up, incident ASCVD events occurred in 431/2876 (15.0%) of those without SMI and 16/66 (24.2%) of those with SMI. In a multivariable-adjusted Cox proportional hazards model, baseline SMI was associated with an increased risk of incident ASCVD events (HR 1.68, 95% CI 1.02-2.77, p = 0.04). However, adding SMI to the PCE did not improve discrimination and reclassification was modest-net reclassification improvement was 0.0161 (95% CI 0.002-0.034, p = 0.08). CONCLUSION: Our findings suggest that the prevalence of SMI is 2.2% among those without known clinical cardiovascular disease considered intermediate-risk by the PCE. In our analysis, SMI only modestly improved classification of risk, suggesting that it may not be very useful as an ASCVD risk enhancer.

Obstructive coronary artery disease with a coronary artery calcium score of 0: A case report.

Coronary artery calcium (CAC) scoring has emerged as a useful tool in identifying patients who may benefit from more aggressive risk factor modification and for prognostication. Although a CAC score of 0 is associated with a very low prevalence of obstructive epicardial coronary artery disease and low event rates, it can also provide a false sense of reassurance. We present a case of a 39-year-old woman with a CAC score of 0 obtained as part of a coronary computerized tomography angiography study that was ultimately found to have significant left anterior descending artery disease requiring percutaneous coronary intervention and a stent.

Rest-Activity Rhythms Are Associated With Prevalent Cardiovascular Disease, Hypertension, Obesity, and Central Adiposity in a Nationally Representative Sample of US Adults.

BACKGROUND: Rest-activity rhythms (RARs), a measure of circadian rhythmicity in the free-living setting, are related to mortality risk, but evidence is limited on associations with cardiovascular disease (CVD) and its risk factors. METHODS AND RESULTS: Participants included 4521 adults from the 2013 to 2014 National Health and Nutrition Examination Survey physical activity monitoring examination. Wrist-worn ActiGraph GT3X+ data were used to estimate RARs. Multivariable logistic models evaluated associations of RARs with prevalent CVD, hypertension, obesity, and central adiposity. Participants (mean age, 49 years) in the highest versus lowest tertile of relative amplitude (greater circadian rhythmicity) had 39% to 62% lower odds of prevalent CVD, hypertension, obesity, and central adiposity. A more active wake period was associated with 19% to 72% lower CVD, hypertension, obesity, and central adiposity odds. Higher interdaily stability (regular sleep-wake and rest-activity patterns) was related to 52% and 23% lower CVD and obesity odds, respectively. In contrast, participants in the highest versus lowest tertile of intradaily variability (fragmented RAR and inefficient sleep) had >3-fold and 24% higher CVD and obesity odds, respectively. A later and less restful sleep period was associated with 36% to 2-fold higher CVD, hypertension, obesity, and central adiposity odds. A statistically significant linear trend was observed for all associations (P-trend<0.05). CONCLUSIONS: A robust, stable, and less fragmented RAR, an active wake period, and an earlier and more restful sleep period are associated with lower prevalent CVD, hypertension, obesity, and central adiposity, with evidence of a dose-response relationship. The magnitude, timing, and regularity of sleep-wake and rest-activity patterns may be important targets for reducing cardiovascular risk.

Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

AIMS: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. METHODS AND RESULTS: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). CONCLUSION: In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Higher levels of small dense particles of LDL cholesterol, better known as the 'bad cholesterol', are associated with a greater risk for the presence of coronary artery calcium, a strong marker for heart disease, even when accounting for estimated total (small dense + large body particles) LDL cholesterol.This risk is stronger in older individuals.Peak risk seems to occur between 49 and 71 mg/dL and does not increase further at higher levels.

High density lipoprotein: When to rethink too much of a good thing.

High density lipoprotein cholesterol (HDL-C) is a known contributor to atherosclerotic cardiovascular disease (ASCVD) risk when HDL-C <40 mg/dL in men and <50 mg/dL in women. There has been much interest in the potential cardioprotective properties of HDL-C, as it removes cholesterol from the periphery to the liver for exertion and holds inherent anti-thrombotic and anti-inflammatory properties. However, clinical trials raising HDL-C pharmacologically have not shown to improve cardiovascular outcomes. In fact, observational studies have demonstrated an increased risk of non-cardiovascular mortality and infection when HDL-C >90 mg/dL and >70 mg/dL in women and men, respectively. The ability for the HDL particle to effectively transport cholesterol from the periphery for excretion in bile is more complex than illustrated on a standard cholesterol panel. There is variability in its function, size, density, subclass, reverse cholesterol transport, and cholesterol efflux capacity, which impact the particles ability to effectively reduce cardiovascular disease (CVD) risk. Research has shown that HDL particles are prone to have a reduction in its efficacy in response to infection, auto-immune disease, menopause and cardiometabolic conditions during pregnancy. Additionally, recent studies have shown that low HDL-C may not adequately influence ASCVD risk in Black adults. The purpose of this contemporary review is to highlight the utility of using HDL-C in assessing CVD risk.

Blood Pressure and Cardiovascular Disease Mortality Among US Adults: A Sex-Stratified Analysis, 1999-2019.

BACKGROUND: Most research examining the association between blood pressure (BP) and cardiovascular disease (CVD) is sex-agnostic. Our goal was to assess sex-specific associations between BP and CVD mortality. METHODS: We combined ten cycles of the National Health and Nutrition Examination Survey (1999-2018), N=53 289. Blood pressure was measured 3× and averaged. Data were linked to National Death Index data, and CVD mortality through December 31, 2019, was defined from International Classification of Diseases, Tenth Revision codes. We estimated sex-stratified, multivariable-adjusted incidence rate ratios (IRRs) for CVD mortality. RESULTS: Over a median follow-up of 9.5 years, there were 2405 CVD deaths. Associations between categories of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with CVD mortality differed by sex (P<0.01). Among men, compared with SBP of 100 to <110 mm Hg, CVD mortality was 76% higher with SBP ≥160 mm Hg (IRR, 1.76 [95% CI, 1.27-2.44]). Among women, compared with SBP 100 to < 110 mm Hg, CVD mortality was 61% higher with SBP 130 to 139 mm Hg (IRR, 1.61 [95% CI, 1.02-2.55]), 75% higher with SBP 140 to 159 mm Hg (IRR, 1.75 [95% CI, 1.09-2.80]), and 113% higher with SBP≥160 mm Hg (IRR, 2.13 [95% CI, 1.35-3.36]). Compared with DBP 70 to <80 mm Hg, CVD mortality was higher with DBP <70 mm Hg and DBP≥80 mm Hg among men, and higher with DBP <50 mm Hg and DBP≥80 mm Hg among women. CONCLUSIONS: The association between BP and CVD mortality differed by sex, with increased CVD mortality risk present at lower levels of systolic blood pressure among women compared with men.

Clinicians' self-reported efficacy in cardiovascular prevention practice in the southeastern United States.

Aim: We assessed self-reported efficacy in cardiovascular prevention practice among internal medicine, family medicine, endocrinology and cardiology clinicians. Patients & methods: We emailed a 21-item questionnaire to 956 physicians, nurse practitioners, physician assistants and pharmacists. Results: 264 clinicians responded (median age: 39 years, 55% women, 47.9% specialists). Most expressed high self-efficacy in lifestyle counselling, prescribing statins, metformin, and aspirin in primary prevention, but low self-efficacy in managing specialized conditions like elevated lipoprotein(a). Compared with specialists, PCPs expressed lower self-efficacy in managing advanced lipid disorders and higher self-efficacy in prescribing sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Conclusion: Self-efficacy in cardiovascular prevention varied across specialties. Future research should explore relevant provider, clinic and system level factors to optimize cardiovascular prevention.

Physical Activity, Coronary Artery Calcium, and Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Although the inverse relationship between physical activity (PA) and cardiovascular disease (CVD) is well established, observational studies suggest that very high levels of PA may be harmful. This study sought to understand the relationship between PA, coronary artery calcium (CAC), and cardiovascular outcomes among individuals at different levels of risk. METHODS: PA and CAC were assessed in 6777 baseline participants of the Multi-Ethnic Study of Atherosclerosis. Total PA in MET-minutes per week was categorized into quartiles, and CAC was categorized as "low risk" (<100 Agatston units; n = 5180) and "high risk" (≥100 Agatston units; n = 1597). Cox proportional hazard regression analyses and Kaplan-Meier curves were generated to understand relationships between PA and CAC with CVD and all-cause mortality. RESULTS: In low-risk participants in the highest PA quartile, there was a decrease in the adjusted hazard ratio (HR) for CVD (HR, 0.72; 95% confidence interval (CI), 0.56-0.94) and all-cause mortality (HR, 0.69; 95% CI, 0.57-0.84) compared with those in the lowest PA quartile. In high-risk participants in the highest PA quartile, there was a decrease in the adjusted HR for all-cause mortality (HR, 0.59; 95% CI, 0.47-0.74) compared with those in the lowest PA quartile. High PA was not associated with an increased risk of either outcome, regardless of CAC category, sex, or race/ethnicity. CONCLUSIONS: Our research suggests that there is no increased risk associated with high levels of PA, even among individuals at high risk of CVD.

Defining preventive cardiology: A clinical practice statement from the American Society for Preventive Cardiology.

Remarkable transformations in science and healthcare have resulted in declines in mortality from cardiovascular disease over the past several decades, largely driven by progress in prevention and treatment of persons at risk. However, these trends are now beginning to stall, as our county faces increases in cardiovascular risk factors including overweight and obesity, type 2 diabetes mellitus, and metabolic syndrome. Furthermore, poor long-term adherence to a healthy lifestyle and lifesaving pharmacotherapy have exacerbated these trends, with recent data suggesting unprecedented increases in cardiovascular morbidity and mortality. A paradigm shift is needed to improve the cardiovascular health of our nation. Preventive cardiology, a growing subspecialty of cardiovascular medicine, is the practice of primordial, primary, and secondary prevention of all cardiovascular diseases. Preventive cardiologists and preventive cardiology specialists are well equipped with the knowledge and skill-set necessary to reduce deaths related to the growing burden of heart disease and its risk factors. Despite dedicated efforts, cardiovascular disease remains the leading killer of men and women in the United States. Although there is little debate regarding the importance of prevention, many healthcare professionals question the need for preventive cardiology as a distinct subspecialty. Additionally, the field's growth has been hampered by a lack of organization and standardization, and variability of training within programs across the country. The purpose of this document is to delineate the key attributes that define the field of preventive cardiology according to the American Society for Preventive Cardiology.

Race, Body Mass Index, and the Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

Background Higher body mass index (BMI) is associated with increased risk of incident atrial fibrillation (AF), but it is not known whether this relationship varies by race/ethnicity. Methods and Results Eligible participants (6739) from MESA (Multi-Ethnic Study of Atherosclerosis) were surveilled for incident AF using MESA hospital surveillance, scheduled MESA study ECG, and Medicare claims data. After a median 13.8 years of follow-up, 970 participants (14.4%) had incident AF. With BMI modeled categorically in a Cox proportional hazards model, only those with grade II and grade III obesity had increased risks of AF (hazard ratio [HR], 1.50; 95% CI, 1.14-1.98, P=0.004 for grade II obesity and HR, 2.13; 95% CI, 1.48-3.05, P<0.0001 for grade III obesity). The relationship between BMI and AF risk was J-shaped. However, the risk of AF as a function of BMI varied substantially by race/ethnicity (P value for interaction=0.02), with Chinese-American participants having a much higher risk of AF with higher BMI and Black participants having minimal increased risk of AF with higher BMI. Conclusions Obesity is associated with an increased risk of incident AF, but the relationship between BMI and the risk of AF is J-shaped and this relationship differs by race/ethnicity, such that Chinese-American participants have a more pronounced increased risk of AF with higher BMI, while Black participants have minimal increased risk. Further exploration of the differential effects of BMI by race/ethnicity on cardiovascular outcomes is needed.

Trajectories of Blood Pressure Control a Year After Randomization and Incident Cardiovascular Outcomes in SPRINT.

BACKGROUND: While studies have assessed the association between blood pressure trajectories and cardiovascular disease (CVD) outcomes using observational data, few have assessed these associations using clinical trial data. We sought to identify systolic blood pressure (SBP) trajectories and to determine if these trajectory patterns carry inherent CVD risk, irrespective of baseline blood pressure. METHODS: SBP trajectories were identified using latent class group-based modeling among a cohort of Systolic Blood Pressure Intervention Trial (SPRINT) participants by incorporating SBP measures during the first 12 months of the trial postrandomization. Cox models were used to evaluate the association between SBP trajectory with CVD and all-cause mortality. RESULTS: Four distinct SBP trajectories were identified: "low decline" (41%), "high decline" (6%), "low stable" (48%), and "high stable" (5%). Relative to the "low decline" group, the "low stable" group was associated with a 29% increased risk of CVD (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.06-1.57) and the "high stable" group was associated with a 76% increased risk of all-cause mortality (HR: 1.76, 95% CI: 1.15-2.68). Relative to the "low stable" group, the "high stable" group was associated with a 54% increased risk of all-cause mortality (HR: 1.54, 95% CI: 1.05-2.28). CONCLUSIONS: Our results demonstrate that SBP trajectory patterns are associated with important cardiovascular outcomes, irrespective of baseline blood pressure, which may help better identify individuals at risk and assist with accurate adjudication of antihypertensive therapy to reduce future events.

Association of Carotid Artery Plaque With Cardiovascular Events and Incident Coronary Artery Calcium in Individuals With Absent Coronary Calcification: The MESA.

BACKGROUND: Absence of coronary artery calcium (CAC) identifies asymptomatic individuals at low cardiovascular disease risk. Carotid artery plaque is a marker of increased risk, but its association with cardiovascular risk and incident CAC in people without CAC is unclear. METHODS: Multi-Ethnic Study of Atherosclerosis participants with CAC score of 0 at enrollment who also underwent carotid plaque measurement using B-mode ultrasonography were prospectively followed for incident coronary heart disease, stroke, and cardiovascular disease events, and CAC (score >0 on up to 3 serial computed tomography scans). The association of carotid plaque presence and plaque score (Ln[score+1]) at baseline with cardiovascular events and incident CAC was evaluated with Cox proportional hazards regression models adjusted for demographics, risk factors, and statin use. RESULTS: Among these 2673 participants (58 years, 64% women, 34% White, 30% Black, 24% Hispanic, and 12% Chinese), carotid plaque at baseline was observed in 973 (36%) and the median plaque score (range, 1-12) among those with plaque was 1. A total of 79 coronary heart disease, 80 stroke, and 151 cardiovascular disease events were observed during 16.1 years of follow-up. Carotid plaque presence and plaque score were independently associated with coronary heart disease risk (HRs, 1.66 [95% CI, 1.04-2.66]; and 1.48 [95% CI, 1.01-2.17], respectively) but not with stroke and cardiovascular disease risk. A total of 973 (36.4%) participants developed CAC over the evaluation period (median 9.3 years). Carotid plaque presence and plaque score were independently associated with incident CAC (HRs, 1.34 [95% CI, 1.18-1.54]; and 1.37 [95% CI, 1.21-1.54]), respectively. CONCLUSIONS: The presence and extent of carotid plaque are associated with long-term coronary heart disease risk and incident CAC among middle-aged asymptomatic individuals with an initial CAC score of 0.

Ten things to know about ten cardiovascular disease risk factors.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The "American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update" is a summary document (updated yearly) regarding CVD risk factors. This "ASPC Top Ten CVD Risk Factors 2021 Update" summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the "ASPC Top Ten CVD Risk Factors 2021 Update" to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.

Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9.

Hypercholesterolemia is a leading cause of cardiovascular disease and mortality in men and women throughout the USA and abroad. The development of statins (HMG-CoA reductase inhibitors) to lower plasma atherogenic cholesterol levels and improve cardiovascular outcomes represents one of the greatest contributions to clinical science in the twentieth century, although residual risk remains even among statin-treated patients. Our understanding of lipid metabolism took a giant leap forward in 2003 with the discovery of proprotein convertase subtilsin/kexin type 9 (PCSK9), a low abundance circulating protein with an outsized effect on the regulation of plasma cholesterol levels. Evolocumab and alirocumab represent the first two US Food and Drug Administration-approved fully human monoclonal antibodies that target PCSK9, which not only lower low-density lipoprotein (LDL) cholesterol to unprecedented levels, but also further improve important cardiovascular outcomes. Small interfering RNA (siRNA) molecules now represent the next generation of drugs designed to antagonize PCSK9. Inclisiran is a siRNA specific for PCSK9 that prevents translation of PCSK9 messenger RNA, leading to decreased concentrations of the protein and lower concentrations of LDL cholesterol. The ORION clinical development program includes several completed and ongoing clinical trials designed to evaluate the safety and efficacy of inclisiran and test its ability to improve hard cardiovascular outcomes. This review discusses the mechanisms of action of inclisiran, examines the current evidence, and provides a comparison of similarities and differences relative to the PCSK9 inhibitors.