Current Medicinal Chemistry - Volume 22, Issue 31, 2015

Atherosclerotic Coronary heart disease (CHD) and non-atherosclerotic CHD in individuals less than 50 years of age is considered a “men’s case”. Undoubtedly, premenopausal women develop atherosclerotic/non-atherosclerotic CHD relatively rarely compared with men. This is attributed mostly to the cardioprotective role of estrogens (mainly estradiol). Nevertheless, there are predisposing conditions, which also make young women vulnerable to develop atherosclerotic/non-atherosclerotic CHD. Women who have classical cardiovascular (CV) risk factors, such as hypertension, diabetes mellitus, smoking, obesity, and dyslipidaemia, are more likely to develop cardiac events, even at a young age. Moreover, there are also other conditions that cause acute coronary syndromes, even in the absence of coronary atheromatic plaques such as myocardial bridge, coronary artery dissection, coronary artery spasm, coronary artery embolism and congenital anomalies of coronary arteries. Also, autoimmune diseases, some of which are more prevalent in women can cause atherosclerotic/ non-atherosclerotic CHD. In this narrative review we have summarized some of the causes that predispose young women to develop atherosclerotic/non-atherosclerotic CHD.

Gender differences have been reported for traditional vascular risk factors such as smoking, obesity, diabetes, hypertension, dyslipidemia, age and family history of premature coronary heart disease. The prevalence, severity, associations and response to treatment of several emerging cardiovascular disease (CVD) risk factors may also differ between men and women. Such CVD risk factors include certain inflammatory and hemostatic markers, endothelial dysfunction, homocysteine, lipid disorders, microalbuminuria/proteinuria, coronary artery calcium score, arterial stiffness, periodontitis, inflammatory bowel syndrome, obstructive sleep apnea, impaired glucose metabolism, metabolic syndrome and non-alcoholic fatty liver disease. Further larger prospective studies are needed to establish these relationships. Hormone replacement therapy may also affect vascular risk. These data should be taken into consideration when assessing and treating CVD risk in women.

Cardiovascular disease (CVD) is a leading cause of death for both women and men. Common traditional risk factors for CVD, such as hypercholesterolemia, hypertension and smoking have a high prevalence in women and in some cases a greater health impact compared with men. Nevertheless, risk factors are treated less often and less aggressively in women than in men, partly due to decreased awareness on the part of public health opinion makers, patients and physicians. About seventy five percent of all coronary heart disease deaths among women could be avoided if CVD risk factors like hypercholesterolemia, hypertension and smoking are adequately treated. This narrative review discusses the treatment of the 4 CVD risk factors, namely hypercholesterolemia, hypertension, smoking and diabetes. These risk factors were examined in the Framingham Heart study and years later they were found in the INTERHEART study to be the 4 most important risk factors for the development of CVD.

There are significant differences in coronary heart disease (CHD) in women whenever a comparison is made to men and these carry over to revascularization procedures including percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. The coronary arteries of women are smaller, which presents additional challenges for PCI and CABG procedures. Unique atypical symptomatology in response to acute coronary syndrome (ACS) in women can confound diagnosis, women notoriously delay seeking medical help for ACS, and physicians and other caregivers have had a tendency to minimize the significance of these symptoms, contributing further to a delay in necessary care. There also appears to be an increased association of inflammation and CHD in women. The younger the female patient with CHD, the higher the mortality and that mortality clearly exceeds that of comparable male patients. For cardiovascular (CV) risk prevention in women, statins have had controversy associated with their use but overall, the proof of beneficial outcomes results from statins is also valid in women. An increased rate of adverse outcomes has been reported in women after PCI and CABG surgery. These worse clinical outcomes have persisted in contemporary years but lessened due to advancement in invasive techniques. Nevertheless, PCI that could improve clinical outcomes in women who have high-risk ACS is, unfortunately, performed on a less frequent basis and, in addition, there are greater delays involving women as compared to men. With increased clinical comorbidity associated with complex CHD in women, a lower anatomical SYNTAX score (from: SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] trial) appears necessary in order for women to achieve a similar long-term mortality benefit from CABG surgery as compared to PCI.

The current treatment regimens for uncomplicated malaria comprise an artemisinin in combination with another drug (ACT). However, the recent emergence of resistance to ACTs in South East Asia dramatically emphasizes the need for new artemisinins. The current artemisinins have been in use since the late 1970s and have relatively poor thermal, chemical and metabolic stabilities - all are metabolized or hydrolyzed in vivo to dihydroartemisinin (DHA) that itself undergoes facile decomposition in vivo. The current artemisinins possess neurotoxicity as demonstrated in animal models, an issue that mandates increased vigilance in view of trends to use of protracted treatment regimens involving sequential administration of different ACTs against the resistant disease. As artemisinins induce the most rapid reduction in parasitaemia of any drug, common sense dictates that any new artemisinin derivative, selected on the bases of more robust chemical and thermal stability, metabolic stability with respect to the generation of DHA in vivo, and relatively benign neurotoxicity should be used in any new ACT whose components are rationally chosen in order to counter resistant malaria and inhibit transmission. 11-Azaartemisinin and its N-substituted derivatives attract because of overall ease of preparation from artemisinin. Some derivatives also possess notable thermal stabilities and although metabolic pathways of the derivatives are as yet unknown, none can provide DHA. The azaartemisinins synthesized over the past 20 years are critically discussed on the basis of their synthetic accessibility and biological activities with the view to assessing suitability to serve as new artemisinin derivatives for treatment of malaria.

The integration of lipoprotein-related or apolipoprotein-targeted nanoparticles as pharmaceutical carriers opens new therapeutic and diagnostic avenues in nanomedicine. The concept is to exploit the intrinsic characteristics of lipoprotein particles as being the natural transporter of apolar lipids and fat in human circulation. Discrete lipoprotein assemblies and lipoprotein-based biomimetics offer a versatile nanoparticle platform that can be manipulated and tuned for specific medical applications. This article reviews the possibilities for constructing drug loaded, reconstituted or artificial lipoprotein particles. The advantages and limitations of lipoproteinbased delivery systems are critically evaluated and potential future challenges, especially concerning targeting specificity, concepts for lipoprotein rerouting and design of innovative lipoprotein mimetic particles using apolipoprotein sequences as targeting moieties are discussed. Finally, the review highlights potential medical applications for lipoprotein-based nanoparticle systems in the fields of cardiovascular research, cancer therapy, gene delivery and brain targeting focusing on representative examples from literature.