A total of 8121 individuals volunteered to participate in the study. Among these subjects, the first 6,738 were invited to attend the clinic and completed the examination. 549 participants (8.1%) were not of Caucasian ethnicity and were excluded from the CoLaus study and 6,189 participants met the inclusion criteria (including ethnicity) and were included in the CoLaus study. As the number of subjects who agreed to participate (8,121) was higher than the number of subjects initially planned for the CoLaus study (6,000), 1,383 could not be included into the study although they were willing to participate. One subject withdrew after consent due to personal reasons. Overall, the final CoLaus sample (n = 6,188) represents 43% of the eligible responders, 41% of all the responders and 31% of the initially sampled population.
The gender and age characteristics of the source population, the initial random sample and the final CoLaus sample are summarized in Table . Overall, both the sampled population and the CoLaus study participants were on average one year younger than the base population, due to an under-representation of subjects aged over 65 years while no differences were found for gender distribution. Further, after excluding non-eligible subjects, no differences were found regarding mean age and gender distribution between the subjects included and the random sample (not shown). The CoLaus Study participants were significantly older (51.1 ± 0.1 vs. 50.8 ± 0.1 years, p < 0.005) than the random sample, while no differences were found for gender distribution (not shown). Age at examination of the participants was on average 2 years higher than age at sampling because of the time elapsed between the two procedures. Distribution of the zip codes within the city was comparable between the base population, the random sample and the CoLaus study participants (not shown).
Distribution of participants by age and sex in the source population, the initial random sample and the CoLaus Study participants.
Socio-economic characteristics of the CoLaus study participants
The CoLaus Study participants' main characteristics are summarized in Table . No gender differences were found regarding the percentage of foreigners. Overall, women were more frequently divorced, widowed or single than men and thus were living more often alone or as a monoparental family (41.7% vs. 23.6%, p < 0.01). Women were also less frequently on a full-time job, more prone to receive social help (26.2% vs. 22.2%, p < 0.001) and had a lower educational level. Among subjects aged less than 40 years old, 48.4% of women had a high school/college/university degree versus 47.4% of men (p < 0.01).
Socio-economic characteristics of the participants in the CoLaus Study.
Clinical characteristics of the CoLaus Study participants
Men had a higher BMI, waist/hip ratio, systolic and DBP levels, but lower body fat percentage, than women. [Table ]. Men had higher total cholesterol and triglyceride levels, but lower HDL cholesterol, than women. Fasting blood glucose levels, homocystein, apolipoprotein B, insulin, NT-proBNP and uric acid were higher in men than in women [Tables and ]. Conversely, women presented higher LDL cholesterol particle size, adiponectin, leptin and hsCRP than men.
Clinical characteristics of the participants in the CoLaus study, by gender.
Clinical characteristics of the participants of the CoLaus study, by gender.
CVRFs within the CoLaus study
More than one third of the overall sample was overweight, and slightly less than one-sixth was obese; overweight and obesity were also more prevalent in men [Table ] and increased with age. In men aged 35–44 years, the prevalence of overweight and obesity were 40.7% and 11.4%, respectively, whereas in men aged 65–75 the corresponding figures were 50.8% and 22.7% (p < 0.001). The corresponding figures for women were 21.9% and 9.6%, and 35.8% and 17.5% (p < 0.001), respectively.
Prevalence of selected cardiovascular risk factors in the participants of the CoLaus study.
Smoking was reporter by 27% of the participants; the prevalence of current smoking was higher in men and tended to decrease with age, from 35.3% among 35–44 year olds to 20.7% among 65–75 year olds in men (p < 0.001), the corresponding figures being 28.1% and 14.7% in women (p < 0.001). Interestingly, in the 45–54 age class, prevalence of smoking was higher in women than in men (30.7% vs. 28.8% (p < 0.001)).
The prevalence of hypertension was 36.7% overall, was higher in men and increased with age: 18.3% and 75.1% in men aged 35–44 and 65–75, respectively (p < 0.001); the corresponding numbers in women were 9.9% and 59.1% (p < 0.001). Among hypertensive subjects, 50.1% were currently taking anti-hypertensive medication. Treatment for hypertension was more frequent in female subjects and increased with age (from 32.2% to 59.4%). Of the treated hypertensive subjects more than half (52.0%) had BP levels ≥ 140/90 mmHg.
High LDL cholesterol, high triglyceride and low HDL cholesterol levels were seen in 20.8%, 12.5% and 2.8% of the subjects, respectively and these conditions were also more prevalent in men. The prevalence of high HDL cholesterol was 53.4% and higher in women than men (71.6% vs. 33.2%). Overall, one third of the sample had dyslipidemia, the prevalence of which was higher in men (42.7%) than in women (26.6%).
Use of statin therapy in subjects with high LDL cholesterol was 5.6%. Prevalence of statin therapy was 69% in subjects after myocardial infarction, 33% in subjects after stroke and 70% in subjects after coronary artery bypass graft. Target level of LDL-cholesterol for secondary prevention, as recommended (< 2.6 mmol/l), was achieved in 28%, 38%, 28% and 33% of the subjects with diabetes, myocardial infarction, stroke and coronary artery bypass graft, respectively.
The overall prevalence of diabetes was 6.6%, and was higher in men. Nine subjects (2.2%) reported to have T1DM. The prevalence of diabetes increased with age, from 2.5% to 17.2% in men aged 35–44 and 65–75, respectively; the corresponding numbers were 1.2% and 9.0% in women with a peak prevalence of 17.2% in men aged > 65. Roughly a third were newly diagnosed diabetics (31.5% for women and 34.7% for men, respectively). The prevalence of IFG in the CoLaus population was 9.8% and was higher in men than in women (14.3% vs. 5.6%).
Treatment for diabetes was present in 73.9% of diabetic subjects but nearly all known diabetics were treated (96.3%). Of the treated diabetic subjects 63.9% had a fasting blood glucose ≥ 7 mmol/L, at the time of their visit.
Finally, 0.7% of women and 2.6% of men reported a personal history of myocardial infarction (p < 0.001); conversely, no gender differences were found regarding personal history of stroke: 1.0% of women vs. 1.3% of men, p = 0.16.
The power of the CoLaus study for an unmatched case-control design to study genotype/phenotype associations depends on the number of cases/controls and estimated effect size [Figure ]. For hypertension with 2268 cases, the estimated power is 0.9 for a 1.4 effect size and 0.5 for a 1.3 effect size. Cases for main CVRFs in the CoLaus study are: dyslipidemia: 2021, obesity: 974, smoking (> 25 cigarettes/day): 746, Type 2 diabetes: 398, coronary heart disease: 262, low HDL: 170. For continuous trait analysis, the example of SBP was taken [Figure ]. For allelic frequencies of 0.2 to 0.4, the study has an estimated power of >0.8 to detect BP variations of 2.0 – 2.3 mm Hg.
Figure 2 Power estimates for the CoLaus study. Power for various sample sizes in unmatched case-control studies. Arbitrary allelic frequency of 0.3, a disease prevalence of 50% and a type 1 error rate of 10-7taking into account 500'000 genetics markers. Curves (more ...)
Figure 3 Power estimates for the CoLaus study. Power for the analysis of systolic blood pressure as a continuous variable. Power calculations using a continuous outcome for independent subjects, with an additive mode of action for the allele and a type 1 error (more ...)