PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data from 9 Studies of Blacks and Whites

PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. Methods and Results - These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites). Conclusions - PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk

Usefulness of Proneurotensin to Predict Cardiovascular and All-Cause Mortality in a United States Population (from the Reasons for Geographic and Racial Differences in Stroke Study)

Cardiovascular disease is a leading cause of death. Proneurotensin is a biomarker associated with the development of cardiovascular disease, cardiovascular mortality, and all-cause mortality. We assessed the association of fasting proneurotensin with mortal events by gender and race (black–white) in a US population. Using a case-cohort subpopulation of the Reasons for Geographic and Racial Differences in Stroke study, fasting proneurotensin was measured on a 1,046-person subcohort and in 651 participants with incident coronary heart disease. Higher proneurotensin was associated with all-cause mortality (hazard ratio [HR] 1.6 per interquartile range, 95% confidence interval [CI] 1.3 to 1.9) and cardiovascular mortality (HR 1.8, 95% CI 1.2 to 2.6). For all-cause and cardiovascular mortality, association was stronger in women (HR 1.9, 95% CI 1.4 to 2.6 and HR 2.5, 95% CI 1.4 to 4.7, respectively) than men (HR 1.4, 95% CI 1.0 to 1.8 and HR 1.4, 95% CI 0.9 to 2.3, respectively), although this difference was not significant. Proneurotensin predicted all-cause mortality in both races and was not predictive of cardiovascular mortality in whites but was in blacks. Proneurotensin was not associated with incident coronary heart disease events. Elevated proneurotensin levels predicted all-cause and cardiovascular mortality in both genders, with a trend toward stronger association in women. Associations were similar in blacks and whites. In conclusion, proneurotensin may be a useful biomarker for all-cause and cardiovascular mortality regardless of race, and it is potentially specific in women. © 201

Supplementary Material for: Healthy Behaviors, Risk Factor Control and Awareness of Chronic Kidney Disease

<b><i>Background/Aims:</i></b> The association between chronic kidney disease (CKD) awareness and healthy behaviors is unknown. We examined whether CKD self-recognition is associated with healthy behaviors and achieving risk-reduction targets known to decrease risk of cardiovascular morbidity and CKD progression. <b><i>Methods:</i></b> CKD awareness, defined as a ‘yes’ response to ‘Has a doctor or other health professional ever told you that you had kidney disease?’, was examined among adults with CKD (eGFR <60 ml/min/1.73 m²) who participated in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Odds of participation in healthy behaviors (tobacco avoidance, avoidance of regular nonsteroidal anti-inflammatory drug use, and physical activity) and achievement of risk-reduction targets (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, systolic blood pressure control and glycemic control among those with diabetes) among those aware versus unaware of their CKD were determined by logistic regression, controlling for sociodemographics, access to care and comorbid conditions. Systolic blood pressure control was defined as <130 mm Hg (primary definition) or <140 mm Hg (secondary definition). <b><i>Results:</i></b> Of 2,615 participants, only 6% (n = 166) were aware of having CKD. Those who were aware had 82% higher odds of tobacco avoidance compared to those unaware (adjusted OR = 1.82, 95% CI 1.02–3.24). CKD awareness was not associated with other healthy behaviors or achievement of risk-reduction targets. <b><i>Conclusions:</i></b> Awareness of CKD was only associated with participation in one healthy behavior and was not associated with achievement of risk-reduction targets. To encourage adoption of healthy behaviors, a better understanding of barriers to participation in CKD-healthy behaviors is needed

PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke Data From 9 Studies of Blacks and Whites

Pathophysiology, epidemiology and therapy of agein