In this work the 5-year incidence rate of hypercholesterolemia was evaluated. In particular, approximately one out of four men and one out of five women that participated in the ATTICA study, developed hypercholesterolemia within this period. The annual incidence rate is about 5% in men and 4% in women, which means that about 900,000 men and women from a total population of 6,5 million people who had had normal cholesterol levels at baseline, developed hypercholesterolemia during the preceding 5 years. Of the baseline factors, increased age, high waist circumference, fasting blood glucose and apolipoprotein B levels, were the most significant determinants of developing hypercholesterolemia.
In the baseline examination (2001–2002), 46% of men and 40% of women had high total cholesterol levels (i.e., >200 mg/dl), and based on these figures it was speculated that about 3,0 million men and women had hypercholesterolemia, in Greece. Based on the present follow up findings, it could be speculated that approximately 180,000 people developed hypercholesterolemia each year, a fact that makes this disorder a very serious problem for the health status of the reference population. The National Health and Nutrition Examination Survey (NHANES) III study [12
] reported that 52% of non-Hispanic white men and 49% of women in USA, had total blood cholesterol levels over 200 mg/dl, rates that are similar to those reported by the ATTICA study. Moreover, several studies have shown that a higher percentage of women than men have total blood cholesterol of 200 mg/dl or higher, beginning at age 50 [13
], which was also observed in the present work since the incidence rate ratio of hypercholesterolemia was higher in women after the age of 55 y (Table ). Taking into account that the prevalence of hypercholesterolemia in the baseline evaluation of the ATTICA study was about 45%, the Seven Countries Study investigators' [15
] reported that in 1980s about 40% of middle-aged Athenian men and women had high total cholesterol levels, while the "Athens Study" investigators [16
] also in early 1980s reported similar results, it is now evident that there is a long-term increasing trend of hypercholesterolemia in Greece. This may attribute to the adherence of a more Westernised lifestyle that observed in Greece during the past two decades, which includes consumption of high – fat foods, adoption of sedentary life and increased cigarette smoking [15
]. Regarding other populations, in a study conducted in another Mediterranean country, Portugal [17
], the investigators reported an incidence of hypercholesterolemia equal to 55.9 cases per 10,000 inhabitants, while there was a higher incidence in men than in women up to the age of 54, but at more advanced ages this relationship was reversed. Although the incidence rates are much lower than those observed in the present study (however, the definition of hypercholesterolemia varied from the one used in this work), a similar trend was observed regarding the men-to-women ratio. Data from the national Nutrition Examination Survey conducted in US from 2001 to 2002, the incidence of combined hypertension and hypercholesterolemia (defined as LDL-cholesterol > 130 mg/dl) was 20% in women and 16% in men, ranging from 1.9% in those aged 20 to 29 years to 56% in those aged greater than 80 years [18
]. The latter study underlined the crucial role of hypertension in combination with high blood lipids levels, which also observed in our study, too.
Oster et al., [19
] reported that depending on age, gender, and initial BMI level, a sustained 10% weight loss would reduce the expected number of years of life with hypercholesterolemia by 0.3 to 0.8, emphasizing the role of body weight on the development of hypercholesterolemia. In the present work it was observed a 2-times higher incidence of hypercholesterolemia among obese individuals compared to normal weight, in both genders. Moreover, waist circumference was one of the most significant predictors of 5-year incidence of hypercholesterolemia (Table ); a 10 cm difference in baseline waist circumference levels was associated with 22% (i.e. 1.0210
) higher risk of hypercholesterolemia within the 5-year period. It is notable that waist circumference was the best predictor among all anthropometric measurements.
Some recent studies have shown that apolipoproteins, and especially apolipoprotein-B/apolipoprotein-AI ratio, predicts cardiovascular risk better than any of the cholesterol indexes [20
]. It is known that apolipoprotein-B is a primary apolipoprotein of low density lipoprotein and it is responsible for carrying cholesterol to tissues. A recent literature-based meta-analysis showed that compared to participants in the lowest tertile of apolipoprotein-B, those in the highest had 99% increased risk of having CHD [21
]. Several investigators have also associated some genetic variations of apolipoprotein-B with the development of hypercholesterolemia and CHD [22
]. In the present analysis apolipoprotein B was the most significant predictor of hypercholesterolemia among all baseline measurements, including blood lipids. Moreover, 34% of the participants with apolipoprotein B levels greater than 100 mg/dl developed hypercholesterolemia within a 5-year period.
Fasting blood glucose levels were also a significant predictor of hypercholesterolemia. Particularly, 30% of participants who had glucose levels greater than 100 mg/dl at baseline examination developed hypercholesterolemia during the aforementioned period. It is already known that non-insulin-dependent diabetes mellitus is often associated with increased triglyceride, LDL-cholesterol and a reduced HDL-cholesterol levels [26
]. According to the National Cholesterol education Program, high total cholesterol is present in 70% of adults with diagnosed diabetes and 77% with undiagnosed diabetes in the US population [28
]. All these findings demonstrate the relationship between diabetic status and hypercholesterolemia; however, the exact mechanisms that relate high blood glucose levels to the incidence of hypercholesterolemia are not fully understood.
Finally, greater adherence to the Mediterranean diet was inversely associated with the development of hypercholesterolemia (Table ). It is known that dietary habits usually influence blood lipids levels [29
]. A traditional dietary pattern that is often consumed in Mediterranean populations has already been related to the reduction of all cause and cardiovascular disease mortality, due to its effect on blood pressure levels, body mass index, platelet aggregation, plasma fibrinogen and other haemostaseological factors [31
]. In this work it was observed a 6% decrease in the risk of hypercholesterolemia per 1 unit increase in the diet score that assessed adherence of the Mediterranean diet, especially in middle aged women. However, when the analysis was stratified by age and sex, the aforementioned relationship was not significant in men of any age and in older (>55 y) women, because of the masking effect of other covariates included in the statistical models.
The baseline evaluation was performed once, and may be prone to measurement error. Thus, the prevalence of hypercholesterolemia or the levels of total serum cholesterol or other blood lipids, at baseline, may be overestimated. However, our methodology is similar to those of other cross – sectional surveys and follow-up epidemiological studies in Europe and the US, and therefore the results are comparable. The relative risks of developing hypercholesterolemia were estimated by the odds ratios through multiple logistic regression analysis, which may lead to an overestimation of the true effect of the investigated factors. Moreover, multiple significance tests were performed (in Table ) that may influenced the significance of the findings; however, the results from the multiple logistic regression analysis were the most reliable. Another limitation is that we have not completed the dietary analysis for nutrient components (including electrolytes), so the role of specific nutrients was not evaluated. Finally, telephone calls for the ascertainment of hypercholesterolemia is valid only when accurate medical records exist; therefore, we assessed the 5-year incidence of known hypercholesterolemia and many individuals that developed hypercholesterolemia during the 5-year period, but they did not know it, were misclassified in the re-examination.