Chlamydia pneumoniae, Antibiotic Treatment, and Early Atherosclerosis

Chlamydia pneumoniae, Antibiotic Treatment, and Early Atherosclerosis

Petru Liuba, MD, PhD and Erkki Pesonen, MD, PhD

Division of Pediatric Cardiology, Lund University Hospital, Lund, Sweden, Petru.Liuba@pedi.lu.se

Ilari Paakkari, MD, PhD

Department of Pharmacology, University of Helsinki, Helsinki, Finland

To the Editor:

Sander et al¹ state that 30-day treatment with roxithromycin attenuates the thickening of carotid artery intima-media in Chlamydia pneumoniae (Cp)–seropositive patients aged >55 years. However, no benefit was observed in the combined incidence of stroke, myocardial infarction, and vascular death. Although the antibiotic therapy reduced C-reactive protein, no reduction in the Cp antibody titers was observed. The authors propose several explanations that might account for these discrepancies.

Another explanation is that Cp might simply have little impact on the arterial wall at this age. The multifactorial etiology of an acute event complicating an atherosclerotic plaque prevails in the elderly because of the potentially increased number of additional risk factors that accumulate with age and with which Cp may interact. We believe that a more effective approach to prevent the clinical manifestations of infection-related atherosclerotic disease is to address younger populations. The following arguments support our theory.

One fundamental issue is that atherosclerosis begins in childhood, and, as shown by serial angiographic studies, ² proceeds in steps, with episodes of vascular growth followed by incomplete healing. This emphasizes the causative role of the repeated acute inflammatory stimuli, eg, acute infection, reinfection, and/or reactivation of a chronic infection, in the early arterial disease. Indeed, such infectious phenotype is commonly encountered in childhood. This also holds true for Cp, herpes viruses, and Helicobacter pylori, which are primarily acquired in childhood. Of note, experimental studies have shown that the arterial injury—particularly in relation to Cp—is greater in younger animals and correlates with the number of repeated exposures.³ Earlier autopsy studies documented the association of acute infections with coronary intimal thickening demonstrable during the first weeks and months of life.⁴ Residual arterial thickening may persist beyond an acute infectious episode, as was recently demonstrated in a carotid ultrasonography study of children with acute systemic infections. ⁵ Antibiotic treatment during the acute infection may lessen the postinfection thickening.⁵

References

1. Sander D, Winbeck K, Klingelhöfer J, et al. Reduced progression of early carotid atherosclerosis after antibiotic treatment and Chlamydia pneumoniae seropositivity. Circulation. 2002; 106: 2428–2433.[Abstract/ Free Full Text]
2. Bruschke A, Kramer J Jr, Bal E, et al. The dynamics of progression of coronary atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. Am Heart J. 1989; 117: 296–305.[Medline]
3. O'Connor S, Taylor C, Campbell LA, et al. Potential infectious etiologies of atherosclerosis: a multifactorial perspective. Emerg Infect Dis. 2001; 7: 780–788. [Medline]
4. Pesonen E, Paakkari I, Rapola J. Infection-associated intimal thickening in the coronary arteries of children. Atherosclerosis. 1999; 142: 425–429. [CrossRef][Medline]
5. Liuba P, Persson J, Luoma J, et al. Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media. Eur Heart J. 2003; 24: 515–521.[Abstract/Free Full Text]

Doxycycline Affects Periodontal Pathogen

1612 Doxycycline Affects Periodontal Pathogen- and High Fat Diet-associated Atherosclerosis M. HOGE¹, B. BISHAYI², M. MADAN², E. MESSAS², and S. AMAR², ¹Boston University, School of Dental Medicine, MA, USA, ²Boston University, MA, USA

OBJECTIVES: - It has been postulated that systemic infection with pathogens such as Porphyromonas gingivalis (Pg) elevate the inflammatory response and increase susceptibility to atherosclerosis. Doxycycline has been known to be a pluripotent drug affecting several cell functions. In particular, it is believed to affect matrix remodeling, an important process involved in the development of atherosclerosis. Thus, we hypothesized that Doxycycline would be beneficial in diet- and/or Pg-induced atherosclerosis.

METHODS: - Apolipoprotein E heterozygous (ApoE+/-) mice were inoculated weekly with Pg and treated with either Doxycycline or saline; animals were fed either a high-fat or normal chow diet. Animals were sacrificed at 14 or 24 weeks and histomorphometric analysis of atheromatous lesions in the proximal aorta and serum cytokine profiling were performed.

RESULTS: Histomorphometric analysis demonstrated that administration of Doxycycline to mice fed a high fat diet and inoculated with Pg resulted in a reduction of mean percentage of proximal aorta occupied by atheromatous plaque lesion from 16.46% +/- 1.69 to 1.141% +/- 0.23 (p<0.05) p="0.106)">

CONCLUSIONS: - Doxycycline inhibits pro-inflammatory cytokines and results in profound reduction in the progression of atherosclerosis in ApoE+/- Pg-inoculated and/or high fat diet fed mice.

Olive oil lowers blood pressure

Olive oil lowers blood pressure
NAPLES, ITALY. Several studies have shown that replacing saturated fat with unsaturated fat in the diet can help lower blood pressure in hypertensive individuals. Research has shown that some unsaturated fats (oils) are more effective in lowering blood pressure than others. Fish oils containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for example, have been found quite effective in lowering both blood pressure and triglyceride levels. Now researchers at the University of Naples report that olive oil is also highly effective in lowering blood pressure.

Their one-year study involved 23 men and women with mild hypertension (systolic pressure less than 165 mm Hg and diastolic pressure less than 104 mm Hg at the start of the study). The participants were randomized into two groups. One group was told to add olive oil to their food after cooking while the other group was told to add sunflower oil (a rich source of linoleic acid). Men added 40 grams/day (approx. four spoonfuls) and women added 30 grams/day (approx. three spoonfuls) to arrive at a diet containing 8368 kJ and 6276 kJ respectively. The overall composition of the diet was 17 per cent protein, 57 per cent carbohydrates, and 26 per cent fat.

The participants' blood pressures were measured every two months. After six months the average systolic blood pressure in the olive oil group had dropped to 127 mm Hg from the 134 mm Hg recorded at the start and the diastolic pressure had dropped from 90 mm Hg to 84 mm Hg. There were no significant changes in the sunflower oil group.

The level of antihypertensive medication was adjusted during the experiment by a separate group of doctors who did not know which diet their patients were following. The ones in the olive oil group were able to reduce their medication use by an average 48 per cent and eight of them were able to discontinue their medications completely. None of the ones in the sunflower oil group were able to discontinue their medications and the average reduction in medication usage was only 4 per cent.

The researchers conclude that a reduction in saturated fat intake combined with the increased use of extra-virgin olive oil lowers the need for antihypertensive medication. They speculate that the high content of polyphenols in olive oil may be a major factor in its beneficial effects.
Ferrara, L. Aldo, et al. Olive oil and reduced need for antihypertensive medications. Archives of Internal Medicine, Vol. 160, March 27, 2000, pp. 837-42