Impaired artery elasticity predicts cardiovascular morbidity and mortality- A longitudinal study in the Vara-Skövde Cohort.

It is still debated whether arterial elasticity provides prognostic information for cardiovascular risk beyond blood pressure measurements in a healthy population. To investigate the association between arterial elasticity obtained by radial artery pulse wave analysis and risk for cardiovascular diseases (CVD) in men and women. In 2002-2005, 2362 individuals (men=1186, 50.2%) not taking antihypertensive medication were included. C2 (small artery elasticity) was measured using the HDI/Pulse Wave CR2000. Data on acute myocardial infarction or stroke, fatal or non-fatal, was obtained between 2002-2019. Cox- regression was used to investigate associations between C2 and future CVD, adjusting for confounding factors such as age, sex, systolic blood pressure, heart rate, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LDL- cholesterol, CRP (C-Reactive Protein), alcohol consumption, smoking and physical activity. At baseline, the mean age of 46 ± 10.6 years and over the follow-up period, we observed 108 events 70 events in men [event rate: 5.9%], 38 in women [event rate: 3.2%]. In the fully adjusted model, and for each quartile decrease in C2, there was a significant increase in the risk for incident CVD by 36%. (HR = 1.36, 95% CI: 1.01-1.82, p = 0.041). The results were accentuated for all men (HR = 1.74, 95% CI: 1.21-2.50, p = 0.003) and women over the age of 50 years (HR = 1.70, 95% CI: 0.69-4.20). We showed a strong and independent association between C2 and CVD in men. In women after menopause, similar tendencies and effect sizes were observed.

Racial Differences and Contributory Cardiovascular and Non-Cardiovascular Risk Factors Towards Chronic Kidney Disease Progression.

Background: The prevalence of advanced chronic kidney disease (CKD) is higher in Black than in White Americans. We evaluated CKD progression in Black and White participants and the contribution of biological risk factors. We included the study of lung function (measured by forced vital capacity [FVC]), which is part of the emerging notion of interorgan cross-talk with the kidneys to racial differences in CKD progression. Methods: This longitudinal study included 2175 Black and 2207 White adult Coronary Artery Risk Development in Young Adults (CARDIA) participants. Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were measured at study year 10 (age 27-41y) and every five years for 20 years. The outcome was CKD progression through no CKD, low, moderate, high, or very high-risk categories based on eGFR and UACR in combination. The association between race and CKD progression as well as the contribution of risk factors to racial differences were assessed in multivariable-adjusted Cox models. Results: Black participants had higher CKD transition probabilities than White participants and more prevalent risk factors during the 20-year period studied. Hazard ratios for CKD transition for Black (vs White participants) were 1.38 from No CKD into ≥ low risk, 2.25 from ≤ low risk into ≥ moderate risk, and 4.49 from ≤ moderate risk into ≥ high risk. Racial differences in CKD progression from No CKD into ≥ low risk were primarily explained by FVC (54.8%), hypertension (30.9%), and obesity (20.8%). In contrast, racial differences were less explained in more severe transitions. Conclusion: Black participants had a higher risk of CKD progression, and this discrepancy may be partly explained by FVC and conventional risk factors.

The association between arterial compliance, as assessed by PTC1 and PTC2 from radial artery waveforms, and age, sex, and race/ethnicity.

BACKGROUND: There is limited literature on differences in arterial compliance, as assessed from arterial pressure waveforms, with age, sex, and race/ethnicity. PTC1 and PTC2 are indices of arterial compliance, which are derived from a Windkessel model of the waveform, relatively easy to obtain, and associated with cardiovascular disease. METHOD: PTC1 and PTC2 were computed from radial artery waveforms from participants of the Multi-Ethnic Study of Atherosclerosis at baseline and again 10 years later. We evaluated the association of PTC1, PTC2, and 10-year change in PTC1 and PTC2 with age, sex, and race/ethnicity. RESULTS: Among 6245 participants in 2000-2002 (mean ±â€ŠSD of age was 62 ±â€Š10 years; 52% female; 38% White, 12% Chinese, 27% Black, and 23% Hispanic/Latino), means ±â€ŠSDs for PTC1 and PTC2 were 394 ±â€Š334 and 94 ±â€Š46 ms. After adjustment for cardiovascular disease risk factors, mean PTC2 was 1.1 ms (95% confidence interval: 1.0, 1.2) lower (arterial stiffness was greater) per year older age, was 22 ms (19, 24) lower for females, and varied by race/ethnicity ( P  < 0.001; e.g., 5 ms lower for Blacks compared with Whites), although the differences were smaller at older ages ( P  < 0.001 for age-sex, P  < 0.001 for age-race/ethnicity interactions). Among 3701 participants with repeat measurements in 2010-2012, arteries had stiffened (mean ±â€ŠSD 10-year decrease in PTC2: 13 ±â€Š46 ms) consistent with cross-sectional age-trend and tended to stiffen less for females and Blacks consistent with cross-sectional age-interactions. CONCLUSION: Differences in arterial compliance by age, sex, and race/ethnicity lend support to identify and act on societal factors that may drive health disparities.

Sleep Irregularity and Subclinical Markers of Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

Background Sleep irregularity has been linked to incident cardiovascular disease. Less is known about associations of sleep regularity with atherosclerosis. We examined cross-sectional associations of actigraphy-assessed sleep duration and sleep timing regularity with subclinical atherosclerosis in the community-based MESA (Multi-Ethnic Study of Atherosclerosis). Methods and Results MESA Sleep Ancillary Study participants (N=2032; mean age, 68.6±9.2 years; 37.9% White) completed 7-day wrist actigraphy. Participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and the ankle-brachial index. Sleep regularity was quantified by the 7-day with-in person SD of sleep duration and sleep onset timing. Relative risk regression models were used to calculate prevalence ratios and 95% CIs. Models are adjusted for demographics, cardiovascular disease risk factors, and other objectively assessed sleep characteristics including obstructive sleep apnea, sleep duration, and sleep fragmentation. After adjustment, compared with participants with more regular sleep durations (SD ≤60 minutes), participants with greater sleep duration irregularity (SD >120 minutes) were more likely to have high coronary artery calcium burden (>300; prevalence ratio, 1.33 [95% CI, 1.03-1.71]) and abnormal ankle-brachial index (<0.9; prevalence ratio, 1.75 [95% CI, 1.03-2.95]). Compared with participants with more regular sleep timing (SD ≤30 minutes), participants with irregular sleep timing (SD >90 minutes) were more likely to have high coronary artery calcium burden (prevalence ratio, 1.39 [95% CI, 1.07-1.82]). Associations persisted after adjustment for cardiovascular disease risk factors and average sleep duration, obstructive sleep apnea, and sleep fragmentation. Conclusions Sleep irregularity, particularly sleep duration irregularity, was associated with several measures of subclinical atherosclerosis. Sleep regularity may be a modifiable target for reducing atherosclerosis risk. Future investigation into cardiovascular risk reduction interventions targeting sleep irregularity may be warranted.

Inter-arm systolic blood pressure difference: non-persistence and association with incident cardiovascular disease in the Multi-ethnic Study of Atherosclerosis.

We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD.

Association of Cardiovascular Health Score With Early- and Later-Onset Diabetes and With Subsequent Vascular Complications of Diabetes.

BACKGROUND Little attention has been paid to how well the American Heart Association's cardiovascular health (CVH) score predicts early-onset diabetes in young adults. We investigated the association of CVH score with early- and later-onset diabetes and with subsequent complications of diabetes. METHODS AND RESULTS Our sample included 4547 Black and White adults in the CARDIA (Coronary Artery Risk Development in Young Adults) study without diabetes at baseline (1985-1986; aged 18-30 years) with complete data on the CVH score at baseline, including smoking, body mass index, physical activity, diet quality, total cholesterol, blood pressure, and fasting blood glucose. Incident diabetes was determined based on fasting glucose, 2-hour postload glucose, hemoglobin A1c, or self-reported medication use throughout 8 visits for 30 years. Multinomial logistic regression was used to assess the association between CVH score and diabetes onset at age <40 years (early onset) versus age ≥40 years (later onset). Secondary analyses assessed the association between CVH score and risk of complications (coronary artery calcium, clinical cardiovascular disease, kidney function markers, diabetic retinopathy, and diabetic neuropathy) among a subsample with diabetes. We identified 116 early- and 502 later-onset incident diabetes cases. Each 1-point higher CVH score was associated with lower odds of developing early-onset (odds ratio [OR], 0.64 [95% CI, 0.58-0.71]) and later-onset diabetes (OR, 0.78 [95% CI, 0.74-0.83]). Lower estimates of diabetic complications were observed per 1-point higher CVH score: 19% for coronary artery calcification≥100, 18% for cardiovascular disease, and 14% for diabetic neuropathy. CONCLUSIONS Higher CVH score in young adulthood was associated with lower early- and later-onset diabetes as well as diabetic complications.

Nontraditional Risk Factors for Progression Through Chronic Kidney Disease Risk Categories: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: There may be nontraditional pathways of chronic kidney disease (CKD) progression that are complementary to classical pathways. Therefore, we aimed to examine nontraditional risk factors for incident CKD and its progression. METHODS: We used the generally healthy population (n = 4382) starting at age 27-41 years in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, which is an observational longitudinal study. Nontraditional risk factors included forced vital capacity, inflammation, serum urate, and serum carotenoids. CKD risk category was classified using the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) measured in 1995-1996 and repeated every 5 years for 20 years: No CKD, low risk, moderate risk, high risk, and very high risk. RESULTS: At baseline, 84.8% had no CKD (eGFR ≥60 mL/min/1.73 m2 and UACR <10 mg/g), 10.3% were in the low risk (eGFR ≥60 and UACR 10-29), and 4.9% had CKD (eGFR <60 and/or UACR ≥ 30). Nontraditional risk factors were significantly associated with the progression of CKD to higher categories. Hazard ratios per standard deviation of the predictor for incident CKD and its progression from the No CKD and low and moderate risk into CKD were inverse for forced vital capacity and serum carotenoids and positive for serum urate, GlycA, and C-reactive protein, the first 3 even after adjustment for conventional risk factors. CONCLUSION: Several nontraditional markers were significantly associated with an increased risk of progression to higher CKD categories in generally healthy young to middle-aged adults.

Progression of Chronic Kidney Disease Risk Categories and Risk of Cardiovascular Disease and Total Mortality: Coronary Artery Risk Development in Young Adults Cohort.

Background Previous studies of worsening chronic kidney disease (CKD) based on declining estimated glomerular filtration rate (eGFR) or increasing urine albumin-creatinine ratio (UACR) are limited to later middle-age and older adults. We examined associations of CKD progression and incident cardiovascular disease (CVD) and mortality in younger adults. Methods and Results We studied 4382 adults in CARDIA (Coronary Artery Risk Development in Young Adults) initially aged 27 to 41 years and prospectively over 20 years. Five-year transition probabilities across CKD risk categories were based on eGFR and UACR measured at each exam. Proportional hazards models predicted incident CVD and all-cause mortality by time-varying CKD risk category, adjusting for demographics and CVD risk factors. Progression of CKD risk categories over 20 years occurred in 28.7% (1256/4382) of participants, driven by increases in UACR, but including 5.8% (n=255) with eGFR<60 mL/min per 1.73 m2 or UACR ≥300 mg/g. Compared with eGFR ≥60 and UACR <10, demographic and smoking-adjusted hazard ratios for CVD were 1.62 (95% CI, 1.21-2.18) for low CKD risk (eGFR ≥60 with UACR 10-29) and 13.65 (95% CI, 7.52-24.79) for very high CKD risk (eGFR <30 or eGFR 30-44 with UACR 30-299; or eGFR 30-59 with UACR ≥300). Corresponding hazard ratios for all-cause mortality were 1.42 (95% CI, 1.08-1.88) and 14.75 (95% CI, 9.97-21.82). Although CVD associations were attenuated after adjustment for mediating CVD risk factors, all-cause mortality associations remained statistically significant. Conclusions Among young to middle-aged adults, progression to higher CKD risk category was common. Routine monitoring eGFR and UACR holds promise for prevention of CVD and total mortality.

Simple Nutrient-Based Rules vs. a Nutritionally Rich Plant-Centered Diet in Prediction of Future Coronary Heart Disease and Stroke: Prospective Observational Study in the US.

To better understand nutrition paradigm shift from nutrients to foods and dietary patterns, we compared associations of a nutrient-based blood cholesterol-lowering diet vs. a food-based plant-centered diet with risk of coronary heart disease (CHD) and stroke. Participants were 4701 adults aged 18-30 years and free of cardiovascular disease at baseline, followed for clinical events from 1985 and 86 to 2018. A plant-centered diet was represented by higher A Priori Diet Quality Score (APDQS). A blood cholesterol-lowering diet was represented by lower Keys Score. Proportional hazards regression was used to calculate hazard ratios (HR). Higher APDQS showed a nutrient-dense composition that is low in saturated fat but high in fiber, vitamins and minerals. Keys Score and APDQS changes were each inversely associated with concurrent plasma low-density lipoprotein cholesterol (LDL-C) change. Over follow-up, 116 CHD and 80 stroke events occurred. LDL-C predicted CHD, but not stroke. APDQS, but not Keys Score, predicted lower risk of CHD and of stroke. Adjusted HRs (95% CIs) for each 1-SD higher APDQS were 0.73 (0.55-0.96) for CHD and 0.70 (0.50-0.99) for stroke. Neither low dietary fat nor low dietary carbohydrate predicted these events. Our findings support the ongoing shift in diet messages for cardiovascular prevention.

Atrial Fibrillation and Hypertension: "Quo Vadis".

Hypertension is one of the most well-established risk factors for atrial fibrillation. Longstanding untreated hypertension leads to structural remodeling and electrophysiologic alterations, causing an atrial myopathy that forms a vulnerable substrate for the development and maintenance of atrial fibrillation. Hypertension-induced hemodynamic, inflammatory, hormonal, and autonomic changes all appear to be important contributing factors. Furthermore, hypertension is also associated with several atrial fibrillation-related comorbidities. As such, hypertension may represent an important target for therapy in atrial fibrillation. Clinicians should be aware of the pitfalls of blood pressure measurement in atrial fibrillation. While the auscultatory method is preferred, the use of automated devices appears to be an acceptable method in the ambulatory setting. There are pathophysiologic basis and emerging clinical evidence suggesting the benefit of renin-angiotensin system inhibition in risk reduction of atrial fibrillation development, particularly in patients with left ventricular hypertrophy or left ventricular dysfunction. A better understanding of hypertension's pathophysiologic link to atrial fibrillation may lead to the development of novel therapies for the primary prevention of atrial fibrillation. Finally, future studies are needed to address the strategies of optimal blood pressure to minimize the risk of atrial fibrillation-related complications.

Association of Abdominal Aorta Calcium and Coronary Artery Calcium with Incident Cardiovascular and Coronary Heart Disease Events in Black and White Middle-Aged People: The Coronary Artery Risk Development in Young Adults Study.

Background Assessing coronary artery calcium (CAC) is among AHA/ACC prevention guidelines for people at least 40 years old at intermediate risk for coronary heart disease (CHD). To study enhanced risk stratification, we investigated the predictive value of abdominal aorta calcium (AAC) relative to CAC for cardiovascular disease (CVD) and CHD events in Black and White early middle-aged participants, initially free of overt CVD. Methods and Results In the CARDIA (Coronary Artery Risk Development in Young Adults) study, a multi-center, community-based, longitudinal cohort study of CVD risk, the CAC and AAC scores were assessed in 3011 participants in 2010-2011 with follow-up until 2019 for incident CVD and CHD events. Distributions and predictions, overall and by race, were computed. During the 8-year follow-up, 106 incident CVD events (55 were CHD) occurred. AAC scores tended to be much higher than CAC scores. AAC scores were higher in Black women than in White women. CAC predicted CVD with HR 1.77 (1.52-2.06) and similarly for AAC, while only CAC predicted CHD. After adjustment for risk factors and calcium in the other arterial bed, the association of CAC with CVD was independent of risk factors and AAC, while the association of AAC with CVD was greatly attenuated. However, AAC predicted incident CVD when CAC was 0. Prediction did not vary by race. Conclusions AAC predicted CVD nearly as strongly as CAC and could be especially useful as a diagnostic tool when it is an incidental finding or when no CAC is found.

Early cardiovascular structural and functional abnormalities as a guide to future morbid events.

AIMS: Our aim was to evaluate the predictive value of a battery of 10 non-invasive tests of cardiovascular structural and functional health on the future risk of cardiovascular morbid events. METHODS AND RESULTS: A total of 1900 asymptomatic adults concerned about their risk for cardiovascular disease underwent non-invasive assessment with 10 tests of vascular and cardiac structure and function. A disease score (DS) was calculated for each individual based on these 10 tests. Follow-up (mean 9.2 years) for cardiovascular morbidity and mortality was available for 1442 individuals (mean age 53.2 years, 48.2% women). Those in the lowest DS tertile (0-2) experienced 0.16 cardiovascular events per 100 patient-years (PY), those in the middle tertile (3-5) experienced 0.86 events per 100 PY, and those in the highest tertile (6+) experienced 1.3 events per 100 PY (p < .001). Sensitivity analysis, assuming a neutral effect of DS on projected events in subjects not followed, did not alter statistical significance. Risk assessment using the Framingham risk score (FRS) also predicted morbid events but the two methods differed in identifying individuals at high risk. The net reclassification index was improved by 0.11 (p = 0.01) when DS was added to FRS. CONCLUSIONS: Assessing the biological disease process in the arteries and heart of asymptomatic adults provides a guide to the risk of a future cardiovascular morbid event. Larger and longer studies are needed to determine whether risk factor algorithms, the severity of the biological process or some combination is the optimal method for identifying individuals in need of intervention to delay morbid events.

Plant-Centered Diet and Risk of Incident Cardiovascular Disease During Young to Middle Adulthood.

Background The association between diets that focus on plant foods and restrict animal products and cardiovascular disease (CVD) is inconclusive. We investigated whether cumulative intake of a plant-centered diet and shifting toward such a diet are associated with incident CVD. Methods and Results Participants were 4946 adults in the CARDIA (Coronary Artery Risk Development in Young Adults) prospective study. They were initially 18 to 30 years old and free of CVD (1985-1986, exam year [year 0]) and followed until 2018. Diet was assessed by an interviewer-administered, validated diet history. Plant-centered diet quality was assessed using the A Priori Diet Quality Score (APDQS), in which higher scores indicate higher consumption of nutritionally rich plant foods and limited consumption of high-fat meat products and less healthy plant foods. Proportional hazards models estimated hazard ratios of CVD associated with both time-varying average APDQS and a 13-year change in APDQS score (difference between the year 7 and year 20 assessments). During the 32-year follow-up, 289 incident CVD cases were identified. Both long-term consumption and a change toward such a diet were associated with a lower risk of CVD. Multivariable-adjusted hazard ratio was 0.48 (95% CI, 0.28-0.81) when comparing the highest quintile of the time-varying average ADPQS with lowest quintiles. The 13-year change in APDQS was associated with a lower subsequent risk of CVD, with a hazard ratio of 0.39 (95% CI, 0.19-0.81) comparing the extreme quintiles. Similarly, strong inverse associations were found for coronary heart disease and hypertension-related CVD with either the time-varying average or change APDQS. Conclusions Consumption of a plant-centered, high-quality diet starting in young adulthood is associated with a lower risk of CVD by middle age.

A Plant-Centered Diet and Markers of Early Chronic Kidney Disease during Young to Middle Adulthood: Findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Cohort.

BACKGROUND: Few studies have evaluated whether plant-centered diets prevent progression of early stage chronic kidney disease (CKD). OBJECTIVES: We examined the association between plant-centered diet quality and early CKD markers. METHODS: We prospectively examined 2869 black and white men and women in the Coronary Artery Risk Development in Young Adults Study free of diagnosed kidney failure in 2005-2006 [examination year 20 (Y20); mean age: 45.3 ± 3.6  y]. CKD marker changes from Y20 to 2015-2016 (Y30) were considered, including estimated glomerular filtration rate (eGFR; serum creatinine), urinary albumin-to-creatinine ratio (ACR), and both. Diet was assessed through interviewer-administered diet histories at Y0, Y7, and Y20, and plant-centered diet quality was quantified with the A Priori Diet Quality Score (APDQS). Linear regression models were used to examine the association of APDQS and subsequent 10-y changes in CKD markers. RESULTS: After adjustment for sociodemographic, behavioral, and diet factors, we found that higher APDQS was related to less adverse changes in CKD markers in the subsequent 10-y period. Compared with the lowest APDQS quintile, the highest quintile was associated with an attenuated increase in lnACR (-0.25 mg/g; 95% CI: -0.37, -0.13 mg/g; P-trend < 0.001), whereas the highest quintile was associated with an attenuated decrease in eGFR (4.45 mL·min-1·1.73 m-2; 95% CI: 2.46, 6.43 mL·min-1·1.73 m-2). There was a 0.50 lower increase in combined CKD markers [ln(ACR) z score - eGFR z score] when comparing the extreme quintiles. Associations remained similar after further adjustment for hypertension, diabetes, and obesity as potential mediating factors. The attenuated worsening CKD marker changes associated with higher APDQS strengthened across increasing initial CKD category; those with the best diet and microalbuminuria in Y10-Y20 returned to high normal albuminuria (all P-interaction < 0.001). CONCLUSIONS: Individuals who consumed plant-centered, high-quality diets were less likely to experience deterioration of kidney function through midlife, especially among participants with initial stage characterized as mild CKD.

Serum Urate Trajectory in Young Adulthood and Incident Cardiovascular Disease Events by Middle Age: CARDIA Study.

[Figure: see text].

The association between indices of blood pressure waveforms (PTC1 and PTC2) and incident heart failure.

OBJECTIVES: The radial artery pulse waveform is a continuous measure of pressure throughout the cardiac cycle, and thus can provide more information than just systolic and diastolic blood pressures. New indices based on a Windkessel model of the waveform, PTC1 and PTC2, are related to arterial compliance and add information for prediction of incident cardiovascular disease (coronary heart disease, stroke, myocardial infarction) but their association with heart failure is unknown. METHODS: Among 6229 adults (mean age 62 years) from four race/ethnic groups who were initially free of clinical cardiovascular disease and heart failure in 2000-2002, we evaluated the associations of baseline PTC1 and PTC2 with incident heart failure. RESULTS: Mean ±â€Šstandard deviation PTC1 and PTC2 were 394 ±â€Š334 and 94 ±â€Š46 ms, respectively. During a median of 15.7 years follow-up, there were 357 heart failure events (148 with reduced, 150 with preserved, and 59 with unknown ejection fraction). After adjustment for traditional risk factors, the hazard ratio for heart failure per 1 standard deviation higher PTC2 was 0.73 (95% confidence interval: 0.63--0.85). Higher PTC2 was also significantly associated with lower risk of heart failure with reduced ejection fraction (hazard ratio = 0.67; 95% confidence interval: 0.56--0.80). There was no evidence of a significant association between PTC2 and heart failure with preserved ejection fraction or between PTC1 and heart failure. CONCLUSION: The PTC2 measure of the radial artery pulse waveform may represent a novel phenotype related to heart failure, especially heart failure with reduced ejection fraction.

Cardiovascular Outcomes and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: Current Data and Future Prospects.

Cardiovascular (CV) disease remains the leading cause of morbidity and mortality worldwide and poses an ongoing challenge with the aging population. Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), and the expert consensus is the use of statin therapy (if tolerated) as first line for LDL-C reduction. However, patients with ASCVD may experience recurrent ischemic events despite receiving maximally tolerated statin therapy, including those whose on-treatment LDL-C remains ≥70 mg/dL, patients with familial hypercholesterolemia, high-risk subgroups with comorbidities such as diabetes mellitus, and those who have an intolerance to statin therapy. Optimal therapeutic strategies for this unmet need should deploy aggressive lipid lowering to minimize the contribution of dyslipidemia to their CV risk, particularly for very high-risk populations with additional risk factors beyond hypercholesterolemia and established ASCVD. To understand the current clinical climate and guidelines regarding ASCVD, we primarily searched PubMed for articles published in English regarding lipid-lowering therapies and CV risk reduction, including emerging therapies, and CV outcomes trials with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This review discusses the findings of recent clinical trial evidence for CV risk reduction with cholesterol-lowering therapies, with a focus on CV outcomes trials with PCSK9 inhibitors, and considers the impact of the study results for secondary prevention and future strategies in patients with hypercholesterolemia and CV risk despite maximally tolerated statin therapy.