Sex differences in lipoprotein metabolism and dietary response: Basis in hormonal differences and implications for cardiovascular disease

The transport of fat in the blood stream is approximately twice as fast in women as men. Disease states such as obesity and diabetes are associated with greater lipoprotein abnormalities in women compared with men. A greater increment in cardiovascular disease risk in women is linked to these abnormalities. A greater change in triglyceride level and a lesser change in lowdensity lipoprotein are observed in women than men with high-carbohydrate or high-fat feeding. Most consistent are greater changes in high-density lipoprotein (HDL), HDL2, and apolipoprotein A-I levels in women compared with men with high-carbohydrate or highfat feeding. Dietary fat restriction in women appears to have a less beneficial lipoprotein effect than in men. Dietary fat restriction for heart disease prevention may be less ideal in women than in men.     

Gender differences in cardiovascular response to dementia caregiving

PURPOSE: This study examined gender differences in cardiovascular responses to laboratory-based stress, as well as in ambulatory hemodynamic (i.e., blood pressure and heart rate) functioning among caregivers of persons with dementia. DESIGN & METHODS: Participants were 25 men and 25 women caregivers, matched on age, type of care recipient's dementia, and relationship to the care recipient. After cardiovascular reactivity to a laboratory-based caregiving stressor was assessed, the ambulatory hemodynamic functioning levels of caregivers were measured in caregivers' natural environments. RESULTS: Female caregivers displayed greater systolic and diastolic blood pressure reactivity to a laboratory-based stress task (i.e., discussing caregiving difficulties) compared with male caregivers (p < or =.01). In contrast, no gender differences were found for ambulatory hemodynamic functioning when aggregated overall or when in the presence of the care recipient. IMPLICATIONS: Laboratory-based findings suggest that female caregivers experience greater blood pressure reactivity to caregiving-related stress than do male caregivers. However, these laboratory-based gender differences may not generalize to differences in hemodynamic functioning in caregivers' daily lives.     

Lumenal lipid metabolism: implications for lipoprotein assembly

Overproduction of apolipoprotein B (apoB)-containing lipoproteins by the liver and the intestine is 1 of the hallmarks of insulin resistance and type 2 diabetes and a well-established risk factor of cardiovascular disease. The assembly of apoB lipoproteins is regulated by the availability of lipids that form the neutral lipid core (triacylglycerol and cholesteryl ester) and the limiting lipoprotein monolayer (phospholipids and cholesterol). Although tremendous advances have been made over the past decade toward understanding neutral lipid and phospholipid biosynthesis and neutral lipid storage in cytosolic lipid droplets (LDs), little is known about the mechanisms that govern the transfer of lipids to the lumen of the endoplasmic reticulum for apoB lipidation. ApoB-synthesizing organs can deposit synthesized neutral lipids into at least 3 different types of LDs, each decorated with a subset of specific proteins: perilipin-decorated cytosolic LDs, and 2 types of LDs formed in the lumen of the endoplasmic reticulum, the secretion-destined LDs containing apoB, and resident lumenal LDs coated with microsomal triglyceride transfer protein and exchangeable apolipoproteins. This brief review will address the current knowledge of lumenal lipid metabolism in the context of apoB assembly and lipid storage.     

Gender,ethnicity, and genes in cardiovascular disease. Part 2: implications for pharmacotherapy

Women are underrepresented in clinical trials. Lower doses of beta-blockers are required for Southeast Asians. ACE and ARB's are teratogenic in the second trimester. Torsades de Pointes is more common in women related to a longer QT-interval. Lower dose OCPs decrease the risk of MI, stroke and thrombosis. HRTs are not effective for CAD prevention.     

Neurocardiology: therapeutic implications for cardiovascular disease

The term "neurocardiology" refers to physiologic and pathophysiological interplays of the nervous and cardiovascular systems. This selective review provides an update about cardiovascular therapeutic implications of neurocardiology, with emphasis on disorders involving primary or secondary abnormalities of catecholamine systems. Concepts of scientific integrative medicine help understand these disorders. Scientific integrative medicine is not a treatment method or discipline but a way of thinking that applies systems concepts to acute and chronic disorders of regulation. Some of these concepts include stability by negative feedback regulation, multiple effectors, effector sharing, instability by positive feedback loops, allostasis, and allostatic load. Scientific integrative medicine builds on systems biology but is also distinct in several ways. A large variety of drugs and non-drug treatments are now available or under study for neurocardiologic disorders in which catecholamine systems are hyperfunctional or hypofunctional. The future of therapeutics in neurocardiology is not so much in new curative drugs as in applying scientific integrative medical ideas that take into account concurrent chronic degenerative disorders and interactions of multiple drug and non-drug treatments with each other and with those disorders.     

The role of dietary salt in metabolism and energy balance: Insights beyond cardiovascular disease

Dietary salt (NaCl) is essential to an organism's survival. However, today's diets are dominated by excessive salt intake, which significantly impacts individual and population health. High salt intake is closely linked to cardiovascular disease (CVD), especially hypertension, through a number of well-studied mechanisms. Emerging evidence indicates that salt overconsumption may also be associated with metabolic disorders. In this review, we first summarize recent updates on the mechanisms of salt-induced CVD, the effects of salt reduction and the use of salt substitution as a therapy. Next, we focus on how high salt intake can impact metabolism and energy balance, describing the mechanisms through which this occurs, including leptin resistance, the overproduction of fructose and ghrelin, insulin resistance and altered hormonal factors. A further influence on metabolism worth noting is the reported role of salt in inducing thermogenesis and increasing body temperature, leading to an increase in energy expenditure. While this result could be viewed as a positive metabolic effect because it promotes a negative energy balance to combat obesity, caution must be taken with this frame of thinking given the deleterious consequences of chronic high salt intake on cardiovascular health. Nevertheless, this review highlights the importance of salt as a noncaloric nutrient in regulating whole-body energy homeostasis. Through this review, we hope to provide a scientific framework for future studies to systematically address the metabolic impacts of dietary salt and salt replacement treatments. In addition, we hope to form a foundation for future clinical trials to explore how these salt-induced metabolic changes impact obesity development and progression, and to elucidate the regulatory mechanisms that drive these changes, with the aim of developing novel therapeutics for obesity and CVD.     

Gender and racial differences in lipoprotein subclass distributions: the STRRIDE study

Recent research has focused on the potential atherogenicity of various lipoprotein subclasses and their link to coronary heart disease (CHD) risk. This investigation seeks to identify differences in lipoprotein subclass distributions among a biracial, middle-aged population, while controlling for a number of confounding risk factors. Fasting plasma samples were analyzed in 285 sedentary, mildly dyslipidemic, overweight individuals between 40 and 65 years with no known history of CHD or diabetes. Women had lower levels of small and medium LDL, medium VLDL, large VLDL, and small HDL with a much higher concentration of large HDL than men. Whites had significantly more IDL, small LDL, medium VLDL, and large VLDL with lower levels of large LDL than blacks. HDL and LDL size were larger among blacks and women; VLDL size was greater among whites and men. There was also a trend for men to have more LDL particles than women and whites to have a higher LDL particle concentration than blacks. Within this homogenous population, there were distinct differences between gender and racial groups. Blacks and women had less atherogenic profiles than whites and men, which was not evident from the standard lipid panel.     

A review of the role of apolipoprotein C-II in lipoprotein metabolism and cardiovascular disease

The focus of this review is on the role of apolipoprotein C-II (apoC-II) in lipoprotein metabolism and the potential effects on the risk of cardiovascular disease (CVD). We searched PubMed/Scopus for articles regarding apoC-II and its role in lipoprotein metabolism and the risk of CVD. Apolipoprotein C-II is a constituent of chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein (HDL). Apolipoprotein C-II contains 3 amphipathic α-helices. The lipid-binding domain of apoC-II is located in the N-terminal, whereas the C-terminal helix of apoC-II is responsible for the interaction with lipoprotein lipase (LPL). At intermediate concentrations (approximately 4 mg/dL) and in normolipidemic subjects, apoC-II activates LPL. In contrast, both an excess and a deficiency of apoC-II are associated with reduced LPL activity and hypertriglyceridemia. Furthermore, excess apoC-II has been associated with increased triglyceride-rich particles and alterations in HDL particle distribution, factors that may increase the risk of CVD. However, there is not enough current evidence to clarify whether increased apoC-II causes hypertriglyceridemia or is an epiphenomenon reflecting hypertriglyceridemia. A number of pharmaceutical interventions, including statins, fibrates, ezetimibe, nicotinic acid, and orlistat, have been shown to reduce the increased apoC-II concentrations. An excess of apoC-II is associated with increased triglyceride-rich particles and alterations in HDL particle distribution. However, prospective trials are needed to assess if apoC-II is a CVD marker or a risk factor in high-risk patients.     

Gender differences in cellular response.

Autoimmune and other diseases frequently manifest a sexual discordance that cannot be explained by hormonal differences. Although there is evidence for gender skewing being caused by gonadal hormones, such skewing does not explain an increase of frequency rather than of severity of such diseases in women. To examine if skewing might have a genetic explanation, we have asked how male and female cells devoid of hormonal differences respond to challenges. We used mouse embryonic cells from heart, liver and brain and assessed cellular responsiveness by cell survival. We find that female cells in general show more sensitivity to challenges, such as ethanol, hydrogen peroxide, and camptothecin. Our findings indicate that there is a differential behavior to challenges, in male vs female cells, which may be due to differences in the biological make-up of the cells with regard to gender, and provide preliminary information regarding the feasibility of this type of approach.     

Smoking and smoking cessation -- the relationship between cardiovascular disease and lipoprotein metabolism: a review

Cigarette smoking is generally accepted as the most preventable cause of death in the United States today. Individuals who smoke experience a wide range of physiologic side effects that increase the risk of cardiovascular disease (CVD), including insulin resistance, elevated catecholamine levels which contribute to an elevated heart rate and blood pressure, and hypercholesterolemia. The link between hypercholesterolemia and cardiovascular disease has been extensively researched and is undeniable. What is more, this link is strengthened in smokers as cigarette smoking is known to increase total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), while acting to decrease the cardio-protective high-density lipoprotein (HDL). Alterations in the enzymes that control lipid transport may be a key underlying mechanism contributing to these health destroying effects. This review examines the current literature related to: (1) smoking, lipoproteins, and lipid-related enzymes; (2) the impact of nicotine, carbon monoxide and free radicals on physiologic parameters related to health; and (3) metabolic issues involving smoking cessation and nicotine replacement therapy.     

Gender and cardiovascular disease recent insights

Cardiovascular disease is rare in premenopausal women compared with men in similar age groups. After menopause, however, the gender difference in cardiovascular disease diminishes, and there is an increased incidence of coronary risk and events in women. Although a number of factors contribute to the development of atherosclerotic disease in women, estrogen replacement therapy reduces cardiovascular risk. Potential molecular mechanisms for the antiatherosclerotic effects of estrogen are discussed here. It is proposed that lipid-lowering and antioxidant properties of estrogen synergize to elicit the observed vasoprotective effects. These processes are discussed in the context of balloon-injury models and hypercholesterolemia. (Trends Cardiovasc Med 1997;7:94-100). ? 1997, Elsevier Science Inc.     

Low-density lipoprotein particle number and risk for cardiovascular disease

The key role played by low-density lipoprotein (LDL) particles in the pathogenesis of coronary heart disease (CHD) is well accepted, as is the benefit of lowering LDL in high-risk patients. What remains controversial is whether we are using the best measure(s) of LDL to identify all individuals who would benefit from therapy. Many studies have shown that, at a given level of LDL cholesterol, individuals with predominantly small LDL particles (pattern B) experience greater CHD risk than those with larger-size LDL. However, it is not clear from this observation that small LDL particles are inherently more atherogenic than large ones because, at a given level of LDL cholesterol, individuals with small LDL have more LDL particles in total. The phenotype of small LDL particle size co-segregates with a cluster of metabolic factors, including elevated triglycerides and reduced HDL cholesterol, and in multivariate analyses has generally been found not to be independently associated with CHD risk. In contrast, LDL particle number measured by nuclear magnetic resonance has consistently been shown to be a strong, independent predictor of CHD.     

Kidney disease and cardiovascular disease: implications of dyslipidemia

Cardiovascular complications are common inpatients with kidney disease. Regulating the lipid levels in these patients is important so that the risks of kidney and cardiovascular complications can be minimized. Lipid regulation decreases the incidence of coronary vascular events and other vascular complications in patients with kidney disease; however, whether lipid regulation slows progression of kidney disease is not yet known. Additional studies of the implications of dyslipidemia in patients with kidney disease are needed.