Cardiovascular disease (CVD) is the leading cause of death among women in the United States. As compared with men, women are less likely to be diagnosed appropriately, receive preventive care, or be treated aggressively for CVD. Sex differences between men and women have allowed for the identification of CVD risk factors and risk markers that are unique to women. The 2018 American Heart Association/American College of Cardiology Multi-Society cholesterol guideline and 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD introduced the concept of risk-enhancing factors that are specific to women and are associated with an increased risk of incident atherosclerotic CVD in women. These factors, if present, would favor more intensified lifestyle interventions and consideration of initiation or intensification of statin therapy for primary prevention to mitigate the increased risk. In this primer, we highlight sex-specific CVD risk factors in women, stress the importance of eliciting a thorough obstetrical and gynecological history during cardiovascular risk assessment, and provide a framework for how to initiate appropriate preventive measures when sex-specific risk factors are present.
Apoer2 is an essential receptor in the central nervous system that binds to the apolipoprotein ApoE. Various splice variants of Apoer2 are produced. We showed that Apoer2 lacking exon 16, which encodes the O-linked sugar (OLS) domain, altered the proteolytic processing and abundance of Apoer2 in cells and synapse number and function in mice. In cultured cells expressing this splice variant, extracellular cleavage of OLS-deficient Apoer2 was reduced, consequently preventing γ-secretase-dependent release of the intracellular domain of Apoer2. Mice expressing Apoer2 lacking the OLS domain had increased Apoer2 abundance in the brain, hippocampal spine density, and glutamate receptor abundance, but decreased synaptic efficacy. Mice expressing a form of Apoer2 lacking the OLS domain and containing an alternatively spliced cytoplasmic tail region that promotes glutamate receptor signaling showed enhanced hippocampal long-term potentiation (LTP), a phenomenon associated with learning and memory. However, these mice did not display enhanced spatial learning in the Morris water maze, and cued fear conditioning was reduced. Reducing the expression of the mutant Apoer2 allele so that the abundance of the protein was similar to that of Apoer2 in wild-type mice normalized spine density, hippocampal LTP, and cued fear learning. These findings demonstrated a role for ApoE receptors as regulators of synaptic glutamate receptor activity and established differential receptor glycosylation as a potential regulator of synaptic function and memory.
Objective
Plasma levels of high-density lipoprotein cholesterol (HDL-C) are
strongly inversely associated with coronary artery disease (CAD), and high
HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C
with CAD is an unusual phenotype, and we hypothesized that the HDL in such
individuals may have an altered composition and reduced function when
compared to controls with similarly high HDL-C and no CAD.
Approach
55 subjects with very high HDL-C (mean 86 mg/dL) and onset of CAD
around age 60 with no known risk factors for CAD (‘cases’)
were identified through systematic recruitment. 120 control subjects without
CAD, matched for race, gender, and HDL-C level (‘controls’),
were identified. In all subjects, HDL composition was analyzed and HDL
cholesterol efflux capacity was assessed.
Results
HDL phospholipid composition was significantly lower in cases (92
± 37 mg/dL) than in controls (109 ± 43 mg/dL, p= 0.0095).
HDL cholesterol efflux capacity was significantly lower in cases (1.96
± 0.39) compared with controls (2.11 ± 0.43, p= 0.04).
Conclusions
In persons with very high HDL-C, reduced HDL phospholipid content and
cholesterol efflux capacity is associated with the paradoxical development
of CAD.
Background and aims
Lipoprotein(a) [Lp(a)] is a proatherogenic lipoprotein associated with coronary heart disease, ischemic stroke, and more recently aortic stenosis and heart failure (HF). We examined the association of Lp(a) levels with incident HF hospitalization in the Atherosclerosis Risk in Communities (ARIC) study. We also assessed the relationship between Lp(a) levels and arterial stiffness as a potential mechanism for development of HF.
Methods
Lp(a) was measured in 14,154 ARIC participants without prevalent HF at ARIC visit 1 (1987–1989). The association of Lp(a) quintiles with incident HF hospitalization was assessed using Cox proportional-hazards models. Arterial stiffness parameters were stratified based on Lp(a) quintiles, and p-trend was calculated across ordered groups.
Results
At median follow-up of 23.4 years, there were 2,605 incident HF hospitalizations. Lp(a) levels were directly associated with incident HF hospitalization in models adjusted for age, race, gender, systolic blood pressure, history of hypertension, diabetes, smoking status, body mass index, heart rate, and high-density lipoprotein cholesterol (quintile 5 vs. quintile 1: hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.09–1.41; p-trend across increasing quintiles <0.01), but not after excluding prevalent and incident myocardial infarction cases (HR 1.07, 95% CI 0.91–1.27; p-trend = 0.70). When adjusted for age, gender, and race, Lp(a) quintiles were not significantly associated with arterial stiffness parameters.
Conclusions
Increased Lp(a) levels were associated with increased risk of incident HF hospitalization. After excluding prevalent and incident myocardial infarction, the association was no longer significant. Lp(a) levels were not associated with arterial stiffness parameters.
Background and aims: Diabetes increases risk for atherosclerotic cardiovascular disease (ASCVD). Current guidelines do not recommend measuring lipoprotein(a), another ASCVD risk factor, in these individuals. We examined the association of lipoprotein(a) levels with incident ASCVD events in persons with and without diabetes or prediabetes.
Background: A protective effect of exercise in preventing sudden cardiac death is supported by studies in healthy populations as well as in patients with cardiac disease. The mechanisms involved in this protective effect are unknown. Hypothesis: We hypothesized that exercise conditioning would beneficially alter autonomic nervous system tone, measured by heart rate variability. Methods: We prospectively studied 20 cardiac patients enrolled in a Phase 2 12-week cardiac rehabilitation program following a recent cardiac event. The patients underwent 24 h Holter monitoring at program entry and 12 weeks later. Heart rate variability analysis was assessed for both time domain and spectral analysis. Results: The group demonstrated a modest mean conditioning effect, indicated by an average reduction in resting heart rate from 8 I k 16 to 75 12 beatshin (p = 0.03), and an increase in training METS from 2.1 rt 0.4 to 3.3 f 1.1 (p< 0.OOOl). Overall, 15 of 20 (75%) patients demonstrated increased total and high-frequency power, and mean high-frequency power was significantly increased (3.9 rt 1.4 vs. 4.4 k 1 .O In, p = 0.05). When stratified according to the magnitude of exercise conditioning, patients achieving an increase of > 1 .5 training METS demonstrated significant increases in SDNN, SDANN index, SDNN index, pNN50, total power,
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