**3. ASB and hypertension in healthy women**

Several authors in the first half of the twentieth century have suggested a role of bacteriuria in the etiology of hypertension. For instance, Kass showed small differences in blood pressure between bacteriuric and non-bacteriuric women aged 15 to 64 years old.

The association between ASB and hypertension was investigated in a cohort study of 444 women who were followed for the development of hypertension in relation to *E. coli* bacteriuria at baseline. Hypertension was defined as the (previous) use of antihypertensive medication and/or a measured systolic blood pressure of at least 160 mm Hg or a diastolic blood pressure of 95 mm Hg or higher. A history of having had a heart attack or stroke was assessed at follow-up by the two additional questions: "Have you ever had a heart attack / stroke?". Mean age at baseline was 45.0 ± 3.2 years and 48 women (10%) had *E. coli* bacteriuria. After 11.5 years women who had *E. coli* bacteriuria at baseline had a mean blood pressure at study endpoint of 133 ± 20 mmHg systolic and 78 ± 11 mmHg diastolic, and women without bacteriuria had values of 129 ± 20 and 78 ± 11 mmHg, respectively (p-value for difference 0.33 and 0.88). Interestingly, although *E. coli* bacteriuria was not associated with the blood pressure as a continuous variable, it was associated with the development of hypertension during follow-up (OR 2.8, 95% CI 1.4–5.5). This was mainly due to more bacteriuric women that started antihypertensive drugs when compared to non-bacteriuric participants. This association remained statistically significant after correction for age, weight and creatinine. Eight of the 45 women (18%) who had to be excluded because of the use of antihypertensive medication at baseline, had *E. coli* bacteriuria, which was higher than the percentage of 9% of the final study group without antihypertensive drugs at baseline (p = 0.06). However, no association between ASB and renal function decline was demonstrated. The incidence of heart attacks or strokes was not increased among women with bacteriuria at baseline. These results suggest that bacteriuria increase also the chance to develop hypertension.

No difference in duration until kidney replacing therapy was found between bacteriuric and non-bacteriuric individuals (14.6 versus 13.7 years, p = 0.80). Seven of 49 women who developed renal failure had *E. coli* bacteriuria at baseline, compared to 29 of 206 women in the control group (both 14%). The OR for the development of renal failure in the presence of

In a Swedish study the prevalence of ASB in women was 4%. After 15 years a reinvestigation was carried out, 40 cases (with ASB) and 40 age-matched healthy controls participated. Nobody had developed progressive renal disease. The age-dependent decrease

The results of these longitudinal findings give strong support to the absence of an association between ASB and renal function decline in healthy women. As an explanation, Svanborg et al. found that certain *E. coli* strains stop expressing adherence factors like type 1 and P fimbriae once they have established bacteriuria. Therefore, these strains can remain present in the bladder without triggering an inflammatory response from the host and

In conclusion, no relation between ASB and renal function decline has been demonstrated in healthy women. It has been recommended in American and European guidelines not to screen or to treat ASB in premenopausal non-pregnant women and older persons living in

Several authors in the first half of the twentieth century have suggested a role of bacteriuria in the etiology of hypertension. For instance, Kass showed small differences in blood

The association between ASB and hypertension was investigated in a cohort study of 444 women who were followed for the development of hypertension in relation to *E. coli* bacteriuria at baseline. Hypertension was defined as the (previous) use of antihypertensive medication and/or a measured systolic blood pressure of at least 160 mm Hg or a diastolic blood pressure of 95 mm Hg or higher. A history of having had a heart attack or stroke was assessed at follow-up by the two additional questions: "Have you ever had a heart attack / stroke?". Mean age at baseline was 45.0 ± 3.2 years and 48 women (10%) had *E. coli* bacteriuria. After 11.5 years women who had *E. coli* bacteriuria at baseline had a mean blood pressure at study endpoint of 133 ± 20 mmHg systolic and 78 ± 11 mmHg diastolic, and women without bacteriuria had values of 129 ± 20 and 78 ± 11 mmHg, respectively (p-value for difference 0.33 and 0.88). Interestingly, although *E. coli* bacteriuria was not associated with the blood pressure as a continuous variable, it was associated with the development of hypertension during follow-up (OR 2.8, 95% CI 1.4–5.5). This was mainly due to more bacteriuric women that started antihypertensive drugs when compared to non-bacteriuric participants. This association remained statistically significant after correction for age, weight and creatinine. Eight of the 45 women (18%) who had to be excluded because of the use of antihypertensive medication at baseline, had *E. coli* bacteriuria, which was higher than the percentage of 9% of the final study group without antihypertensive drugs at baseline (p = 0.06). However, no association between ASB and renal function decline was demonstrated. The incidence of heart attacks or strokes was not increased among women with bacteriuria at baseline. These results

the community. The results of these studies confirm these recommendations.

pressure between bacteriuric and non-bacteriuric women aged 15 to 64 years old.

suggest that bacteriuria increase also the chance to develop hypertension.

*E. coli* bacteriuria, corrected for age, was 1.1 (95% CI 0.4–2.8, p = 0.86).

after 15 years was the same in both groups.

**3. ASB and hypertension in healthy women** 

without side effects.

Although more recent studies also found a correlation, only one prospective study has shown that bacteriuria is associated with the development of hypertension. In the above mentioned cohort study, a higher prevalence of hypertension in the bacteriuric group after 12 years of follow-up was found. However, the underlying mechanism of this finding is not clear. Hypertension is a lasting increase in blood pressure with a heterogeneous etiology consisting of both genetic and environmental factors. Patients share the inability to excrete sodium at a normal arterial pressure. If bacteriuria would lead to hypertension, the most attractive explanation would be that hypertension arises secondary to renal scarring caused by the (type 1 fimbriae of the) uropathogens. In the multivariate analysis, correction for creatinine did not change the results, but hypertension can occur before the reduction in creatinine clearance becomes apparent. An alternative explanation is that both bacteriuria and hypertension are found more frequently among individuals with comorbidity or that they share a same (currently unknown) cause. This is supported by the higher prevalence of bacteriuria among women who used antihypertensive drugs at baseline. Given the importance of hypertension the nature of this correlation needs to be studied in future studies.
