Background: There are no ready explanations for differences in ischemic heart disease incidence between women and men under an epidemiological perspective. However, when myocardial infarction occurs, there are more likely individuals who happen to die. Methods: This review from a more recent literature was performed for a two-fold purpose, to describe gender wise: a) the role of classical and novel factors defined to evaluate coronary artery disease (CAD) risk and mortality, aimed at assessing applicability and relevance for primary and secondary prevention; b) the differences in northern versus southern European Countries in risk factors and CAD mortality. Results: Age-related risk patterns differ in men and women. It is uncertain whether standard factors may index CAD risk, including mortality, in different ways and/or whether specific factors might be targeted gender-wise. A list might be compiled: HDL-cholesterol levels, higher in pre-menopausal women than in men, are more strictly related to CAD; high triglycerides and Lp(a) have a similar relationship; HDL-cholesterol levels have an inverse relation with CAD incidence and mortality. The role of statins is not completely defined in primary prevention for women. However, in secondary prevention statins are equally effective in both genders. Weight and glycemic control are effective to reduce cardiovascular disease (CVD) mortality in women from middle to older age. Similarly, CVD mortality in women, from middle to older age, might be reduced by controlling blood pressure, particularly among diabetic or over weighted women. Renal dysfunction, either defined by UAE or eGFR or both may usefully predict primary CVD incidence and risk in both genders. In secondary prediction, kidney dysfunction predicts sudden death in women when left ventricular ejection fraction is also evaluated. Serum uric acid that normally increases with age, differentiates gender-related CVD incidences with a peculiar importance in women as compared to men. There has been much interest to investigate loss of ovarian function in explaining age-related differences between genders. More recently, some emphasis has been laid on the loss of ovarian function-related iron stores. There are subgroups of women as those with mitral valve prolapse and increased circulating levels of catecholamines in whom QT interval, physiologically longer in women than men, may be an arrhythmogenic risk index. However, no large population-based studies were ever conducted to assess this. Therefore, in the future, it will be important to implement risk score instruments (charts and softwares) in women using novel parameters, and among these inflammatory markers and reproductive hormones and serum uric acid. The important results of the WHO MONICA Project confirmed the northern versus southern European gradient in both men and women, for death rates and the proportion of all deaths from cardiovascular causes (including CAD, stroke and other CVD causes). The coronary event rate was initially as high as 1, 000 per 100, 000 inhabitants in Finland and less than 1 fifth of that in Spain with the corresponding figures in women of 200 and 30, respectively. Conclusion: No doubt might still exist that all efforts need be undertaken for both men and women, for health and prolongation of life to effectively treat common risk factors such as cigarette consumption, high blood pressure, cholesterol levels and physical inactivity by also paying attention to optimal diet.