Chlamydia pneumoniae causes heart disease

Chlamydia pneumoniae [Chlamydophila pneumoniae] and atherosclerosis

Studies on the role of Chlamydia pneumoniae and other pathogens in cardiovascular disease appear to be inconsistent, because antibody levels are not a meaningful way to measure clinically relevant parameters of infection. Some statements made by Prof. Pekka Saikku concerning the flaws of seroepidemiology (Epidemiology of Chlamydia penumoniae in atherosclerosis. Am Heart J 1999 Nov;138(5 pt 2):S500-S503):

"The presence of Chlamydia pneumoniae in arteriosclerotic lesions is not always reflected in antibodies." Autopsy studies find many cases in which CPn is detected in lesions, but serum antibodies are not elevated or are even absent. And, higher levels of antibodies could result in less Chlamydia in the lesions.

"...the use of seroepidemiology is nearly worthless in patients in old age, when more or less every person has arteriosclerotic vessels." The ORs of all risk factors, both real and imaginary, tend to disappear at advanced ages.

"...simple antibody level measurements do not reflect the current state of inflammation in the arteriosclerotic placques, which are a risk factor for infarction." C-reactive protein (CRP) indicates the presence of inflammation, but it is not specific for a particular cause.

Epidemics of acute respiratory infections also confuse the picture, by raising antibody levels in persons who do not have chronic infections. Measurement of circulating immune complexes and IgA are suggested as better indicators in seroepidemiologic studies.

Autopsy studies are still the most definitive, such as: Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis. Michael Davidson, C-C Kuo, JP Middaugh, LA Campbell, S-P Wang, WP Newman, III, JC Finley, JT Grayston. Circulation 1998 Aug;98(7):628-633.

"This study was designed to determine whether infection with C pneumoniae, diagnosed by the host C. pneumoniae-specific antibody response, preceded any direct evidence of this organism in coronary artery tissue from low-risk subjects with early disease." Serum specimens that had been drawn a mean of 8.8 years before death were compared with the degree of atheroscerlosis found at autopsy.

Chlamydia pneumoniae was detected in coronary arteries by both PCR and immunocytochemistry (ICC). As a review of previous studies found (P Saikku. Chlamydia pneumoniae and atherosclerosis - an update. Scand J Infect Dis 1997;104(suppl):53-56), ICC was more often positive than PCR.

The 60 cases died at a mean age of 34.1 years, range 15 to 57 years. 97% of the deaths were noncardiovascular: 77% accidental, 10% due to alcohol, and 10% from other causes. All sera were collected for noncardiovascular health screening, including hepatitis, and none were collected for acute respiratory disease investigation (in which CP respiratory infection could have influenced sample selection).

Davidson et al found an OR of 9.40 (95% CI 2.61-33.84) for IgG antibody of 1:256 or more. This OR is large enough to generate spurious risks of the magnitude of those claimed for smoking in studies which did not consider CP infection. Also, in this study, smoking status, as defined by postmortem serum thiocyanate, was "unrelated to either the presence of C pneumoniae organism in coronary arterial tissue (OR, 0.64; 95% CI, 0.15 to 2.77) or to postmortem serum IgG antibody of >/= 1:256 (OR, 0.22; 95% CI, 0.03 to 1.36)."

Another study of antibodies versus findings at autopsy by Ericson et al (Relationship of Chlamydia pneumoniae infection to severity of human coronary atherosclerosis. Circulation 2000 Jun 6;101(22):2568-2571) found that "Elevated IgG and IgA levels against C pneumoniae were not different in cases with severe and mild atherosclerosis (61% and 30% for severe atherosclerosis and 67% and 42% for mild atherosclerosis, respectively.... Serum antibody titers against C pneumoniae do not differentiate between severe and mild atherosclerosis."

The 1998 review of Chlamydia pneumoniae and cardiovascular disease in the Center's for Disease Control's journal, Emerging Infectious Diseases, is free online.

[Chlamydia pneumoniae and Helicobacter pylori infections in acute mycardial infarction]. G Di Tano, I Picerno, ML Calisto, SA Delia, P Lagana, P Spataro. Ital Heart J 2000 Dec;1(12 Suppl):1576-1581.

Association between C-reactive protein, anti-Chlamydia pneumoniae antibodies, and vascular function in healthy adults. N Sharma, JD Rutherford, JT Grayston, LP King, I Jialal, TC Andrews. Am J Cardiol 2001 Jan 1;87(1):119-121, A9. "In subjects with IgA antibodies to C. pneumoniae or detectable levels of C-reactive protein, they found a consistent trend in 'reduced flow-mediated and nitroglycerine-induced vasodilation.'"

[No title]. M Kruk, J Przyluski, TW Deptuch, Z Dzielinska, J Kadziela, E Podsiadly, J Siennicka, W Piotrowski, M Kantoch, S Tylewska-Wierzbanowska, W Ruzyllo. Pol Arch Med Wewn 2001 Jan;105(1):39-44. An association of CP with CAD, but not with restenosis.

Association between Chlamydia pneumoniae and atherosclerotic lesions. JI Phillips, A Shor. Cardiovasc J S Afr 2001 Feb-Mar;12(1):42-46. Review. "Atherosclerotic lesions have been studied in detail, but until recently histological descriptions of the lesions have not included C. pneumoniae organisms."

Correlation between detection methods of Chlamydia pneumoniae in atherosclerotic and non-atherosclerotic tissues. B Maraha, H Berg, GJ Scheffer, A van der Zee, A Bergmans, J Misere, J Kluytmans, M Peeters. Diagn Microbiol Infect Dis 2001 Mar;39(3):139-143.

Association of seropositivity for antibody to Chlamydia-specific lipopolysaccharide and coronary artery disease in Japanese men. K Shimada, H Daida, H Mokuno, Y Watanabe, M Sawano, Y Iwama, E Seki, T Kurata, H Sato, S Ohashi, H Suzuki, K Miyauchi, J Takaya, H Sakurai, H Yamaguchi. Jpn Circ J 2001 Mar;65(3):182-187.

Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis. K Burian, Z Kis, D Virok, V Endresz, Z Prohaszka, J Duba, K Berencsi, K Boda, L Horvath, L Romics, G Fust, E Gonczol. Circulation 2001 Mar 20;103(11):1503-1508.

Distribution of Chlamydia pneumoniae in the human arterial system and its relation to the local amount of atherosclerosis within the individual. A Vink, M Poppen, AH Schoneveld, PJ Roholl, DP de Kleijn, C Borst, G Pasterkamp. Circulation 2001 Mar 27;103(12):1613-1617.

Chlamydia pneumoniae serology: Importance of methodology in patients with coronary heart disease and healthy individuals. A Schumacher, AB Lerkerod, I Seljeflot, L Sommervoll, I Holme, JE Otterstad, H Arnesen. J Clin Microbiol 2001 May;39(5):1859-1864.

[Relationship of Chlamydia pneumoniae infection to severity of coronary atherosclerosis in patients with chronic coronary artery disease and with normal coronary arteries]. S Imai, T Matsubara, T Hori, I Nakagawa, K Ozaki, K Hatada, T Mezaki, A Nasuno, K Kubota, T Tanaka, Y Aizawa. J Cardiol 2001 Jun;37(6):293-299. "[T]he association is less clear in the Japanese population," which is notable for lower rates of coronary artery disease.

Chlamydia pneumoniae seropositivity and hyperhomocysteinemia are linked in patients with atherosclerosis. P Wiesli, FE Maly, A Meniconi, W Czerwenka, U Hoffmann, W Vetter, G Schulthess. Clin Chem 2001;47(7):1304-1306. No abstract.

Chlamydia pneumoniae infection and its association with coronary heart disease and cardiovascular risk factors in a sample South Asian population. S Mendis, YM Arseculeratne, N Withana, S Samitha. Int J Cardiol 2001 Jul;79(2-3):191-196. "The highest geometric mean titre of control subjects was significantly lower compared to AMI patients and SCHD patients," P<0.05 for both before multivariate confounding.

Chlamydia pneumoniae exposure and inflammatory markers in acute coronary syndrome (CIMACS). HR Chandra, N Choudhary, C O'Neill, J Boura, GC Timmis, WW O'Neill. Am J Cardiol 2001 Aug 1;88(3):214-218. "[W]e found a strong association between high level seropositivity to CP and ACS."

Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/p42 mitogen-activated protein kinase activation. S Sasu, D LaVerda, N Qureshi, DT Golenbock, D Beasley. Circ Res 2001 Aug 3;89(3):244-250.

Standardizing Chlamydia pneumoniae assays: Recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada). SF Dowell, RW Peeling, J Boman, GM Carlone, BS Fields, J Guarner, MR Hammerschlag, LA Jackson, CC Kuo, M Maass, TO Messmer, DF Talkington, ML Tondella, SR Zaki. Clin Infect Dis 2001 Aug 15;33(4):492-503.

Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions. M Rassu, S Cazzavillan, M Scagnelli, A Peron, PA Bevilacqua, M Facco, G Bertoloni, FM Lauro, R Zambello, E Bonoldi. Atherosclerosis 2001 Sep;158(1):73-79. CP found in 100% of patients, when 5 different areas were examined; HP in 4/18; CMV in 3/18. [Note that CP in places other than the one at interest would produce antibodies which on analysis would weaken associations.]

Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection. Y Momiyama, R Hirano, H Taniguchi, H Nakamura, F Ohsuzu. J Am Coll Cardiol 2001 Sep;38(3):712-717. In 292 angiography patients, "Odds ratios for CAD were 1.4 in the group with seropositivity alone, 1.7 with the variants alone and 3.8 with seropositivity and the variants."

Potential infectious etiologies of atherosclerosis: a multifactorial perspective. S O'Connor, C Taylor, LA Campbell, S Epstein, P Libby. Emerging Infectious Diseases 2001 Sep-Oct;7(5):780-788. Unfortunately, this establishment perspective does not address the issue of confounding by infection, which prevails in the accepted methods of multivariate statistical analysis.

Incidence of Chlamydia pneumoniae infection in patients with coronary artery disease subjected to angioplasty or bypass surgery. P Pieniazek, E Karczewska, E Stepien, W Tracz, SJ Konturek. Med Sci Monit 2001 Sep-Oct;7(5):995-1001. And: (News) Chlamydia pneumoniae linked to coronary artery disease. M Greener, Doctor's Guide 2001 Oct 15.

Chlamydia pneumoniae seropositivity and systemic and renovascular atherosclerotic disease. AJ van der Ven, MJ Hommels, AA Kroon, A Kessels, K Flobbe, J van Engelshoven, CA Bruggeman, PW de Leeuw. Arch Intern Med 2002 Apr 8;162(7):786-790. In 96 patients with renovascular hypertension, "IgG seropositivity to C pneumoniae was significantly associated with atherosclerosis (odds ratio, 6.0; 95% confidence interval, 1.33-27.5; P=.02)." And: Chlamydia pneumoniae linked to renovascular atherosclerotic disease. Reuters Health 2002 Apr 18 / Medscape.

Hyperhomocyst(e)inemia and Chlamydia pneumoniae IgG seropositivity in patients with coronary artery disease. OH Stanger, HJ Semmelrock, P Rehak, B Tiran, A Meinitzer, B Rigler, A Tiran. Atherosclerosis 2002 May;162(1):157-162. "These data indicate an association between elevated plasma homocyst(e)ine concentrations and chlamydial IgG antibody titers in patients with CAD."

Chlamydia pneumoniae and atherosclerosis - what we know and what we don't. J Ngeh, V Anand, S Gupta. Clinical Microbiology and Infection 2002 Jan;8(1):2-13. REVIEW. "A recent survey in the USA showed how a minority (4%) of physicians (mainly cardiologists) have already started treating cardiovascular diseases with antimicrobial agents as though they were an infectious disease. However, this practice is currently considered premature." Sic - especially by non-cardiologists with a dogmatic loyalty to health fascist blame-the-victim orthodoxy, based onstatistical methods that exploit confounding -cast.

Antibody response to chlamydial death shock protein 60 is strongly associated with acute coronary syndromes. LM Biasucci, G Liuzzo, A Ciervo, A Petrucca, M Piro, DJ Angiolillo, F Crea, A Cassone, A Maseri. Circulation 2003 Jun 24;107(24):3015-3017. "Seropositivity to Cp-HSP60 was found in 99% of ACS patients but in only 20% of SA patients and none of the control subjects.... CONCLUSIONS: Seropositivity for Cp-HSP60 appears to be a very sensitive and specific marker of ACS..."

Involvement of Chlamydia pneumoniae in Atherosclerosis: More Evidence for Lack of Evidence. MM Ieven, VY Hoymans. J Clin Microbiol 2005 Jan;43(1):19–24. A review of the conflicting results and technical difficulties encountered. An issue not addressed is whether atherosclerosis could develop from initial lesions caused by CP, even without continuing infection.

Association between Chlamydia pneumoniae and acute myocardial infarction in young men in the United States military: the importance of timing of exposure measurement. CM Arcari, CA Gaydos, FJ Nieto, M Krauss, KE Nelson. Clin Infect Dis 2005 Apr 15;40(8):1123-1130. 300 male case patients (age, 30-50 years) with a medically documented, first-time hospitalization for acute myocardial infarction (MI) and from whom a serum specimen had been drawn >or=1 year before the time of the acute MI, and 300 matched controls. "Significant risk was associated with high titer (>or=1 : 64) to C. pneumoniae immunoglobulin A (IgA) (adjusted relative risk [RR(adj)], 1.67; 95% confidence interval [CI], 1.04-2.70). This increased risk was greatest when specimens were collected 1-5 years before the event (RR(adj), 2.11; 95% CI, 1.06-4.21). High titer (>or=1 : 256) to C. pneumoniae immunoglobulin G (IgG) was also associated with an elevated risk (RR(adj), 1.74; 95% CI, 0.90-3.34) after full adjustment for cardiovascular risk factors, whereas no independent risk for acute MI was associated with cytomegalovirus IgG seropositivity."

Relationship between peripheral arterial occlusive disease (PAOD) and chronic Chlamydophila (Chlamydia) pneumoniae infection. A meta-analysis. J Gutierrez, J de Dios Luna, J Linares, M del Rosario Montes, E Quesada, A Rojas, MJ Soto, A Sorlozano. Thromb Haemost 2005 Jun;93(6):1153-1160. Meta-analysis of 43 observational case-control studies published before May 2004 on the association between Chlamydophila pneumoniae infection and PAOD. "[B]y immunohistochemical analysis (OR=15.4, 95%CI=5.0-46.9) and nested PCR studies of arterial biopsies (OR=4.3, 95%CI=1.8-10), by PCR study of non-arterial samples (OR=2.9, 95%CI=1.2-7.0), by other direct-detection tests (OR=16.7, 95%CI=7.0-39.8), and by ELISA and MIF tests to detect high IgG (OR=2, 95%CI=1.1-3.5 and OR=1.7, 95%CI=1.0-2.9, respectively) and IgA (OR=1.9, 95%CI=1.1-3.4 and OR=1.5, 95%CI=1.1-2.0, respectively) titers. No significant association was found in simple PCR studies of arterial biopsies, MIF tests to detect low IgG titers or IgM, or ELISA studies to detect IgM."

Close association of Chlamydia pneumoniae IgA seropositivity by ELISA with the presence of coronary artery stenosis in haemodialysis patients. M Nishimura, T Hashimoto, H Kobayashi, T Fukuda, K Okino, N Yamamoto, C Mashida, K Kawagoe, H Fujita, N Inoue, H Takahashi, T Ono. Nephrol Dial Transplant 2005 Sep;20(9):1944-1950. "Coronary stenosis >50% was found in 102 of 161 haemodialysis patients (63.4%). Of the 102 patients, 75.5% were asymptomatic. Seropositivity for C. pneumoniae IgA was found in patients with coronary stenosis (77 out of 102, 75.5%) more frequently (P<0.001) than in patients without coronary stenosis (10 out of 59, 16.9%). Seropositivity for C. pneumoniae IgA but not IgG was strongly associated with the presence of coronary stenosis in multiple logistic regression analysis (odds ratio, 18.440; 95% confidence interval, 7.500–45.337), independently of the Framingham coronary risk factors, factors peculiar to ESRD or serum C-reactive protein levels." Re ELISA versus MIF: "...Hoymans et al. [21] have recently reported that the sandwich ELISA, which is the same as our method, shows good agreement with the microimmunofluorescence method."

Detection of Chlamydia pneumoniae in human aortic tissue: kdtA gene amplification and in vitro hybridization. N Guzman, C Espitia, P Delgado, D Echeverri, L Buitrago, C Jaramillo. Biomedica 2005 Dec;25(4):511-517. "C. pneumoniae was detected in 12 (85.7%) of the 14 aortic tissue samples."

Investigation of Chlamydia pneumoniae DNA, chlamydial lipopolisaccharide antigens, and Helicobacter pylori DNA in atherosclerotic plaques of patients with aortoiliac occlusive disease. I Kaklikkaya, N Kaklikkaya, K Buruk, Z Pulathan, I Koramaz, F Aydin, I Tosun, A Osman Kilic, F Ozcan. Cardiovasc Pathol 2006 Mar-Apr;15(2):105-109. "Chlamydial LPS and DNA were detected in 6 of 21 (28.57%) atherosclerotic lesions using ELISA or PCR, respectively. There was no evidence of H. pylori DNA in any plaque specimens. All cases in which C. pneumoniae DNA was positive were also seropositive for antichlamydial LPS. Neither C. pneumoniae DNA nor antigen nor H. pylori DNA was found in the macroscopically healthy samples."

Detection

Chlamydialike Organisms and Atherosclerosis (letter). G Greub, O Hartung, T Adekambi, YS Alimi, D Raoult. Emerg Infect Dis 2006 Apr;12(4). Parachlamydia acanthamoebae and Neochlamydia hartmanellae (chlamydialike organisms that share ≈86% 16S rRNA sequence similarity with C. pneumoniae) were found in surgical samples from 5 of 27 patients undergoing aortic or carotid surgery for atherosclerotic disease. All of the patients in whom it was found were over 68 years old. There may be cross-reaction between chlamydia and parachlamydia which causes false positives.

Evaluation of serological tests detecting Chlamydophila pneumoniae-specific immunoglobulin M antibody. N Miyashita, Y Obase, M Fukuda, H Shoji, K Mouri, S Yagi, K Yoshida, K Ouchi, M Oka. Intern Med 2006;45(20):1127-1131. A newly developed enzyme-linked immunosorbent assay (ELISA) (Hitazyme C. pneumoniae) had IgM-positive results were observed in 16.5% of patients with stable chronic lung diseases and in 8.6% of asymptomatic healthy subjects. However, there were no positive cases with cell culture, immunoblot or MIF test.

Mechanisms

Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo. J Rupp, T Hellwig-Burgel, V Wobbe, U Seitzer, E Brandt, M Maass. Proc Natl Acad Sci USA 2005 Mar 1;102(9):3447-3452. "Infection of human coronary artery smooth muscle cells with C. pneumoniae significantly induced mRNA and protein for the angiogenic transcription factor Egr-1, resulting in enhanced coronary artery smooth muscle cell proliferation, which was reduced by transfection with small interfering RNA duplexes targeted at Egr-1 mRNA. These effects required viable chlamydiae and depended on p44/42 mitogen-activated protein kinase activity but not on the p38 mitogen-activated protein kinase pathway." "Previously described only in acute vascular damage under physical injury or hypoxia, enhanced Egr-1 expression levels have now been consistently found in atherosclerotic lesions. Because of its dual role as mitogenic stimulus for vascular cells and proatherogenic transcription factor, Egr-1 is now assumed to play a pivotal role in the initiation and progression of atherosclerosis." "...C. pneumoniae seems to be somewhat unique among the potential causal factors, because it may have simultaneously a part in several of the most prominent features of atherogenesis: It may initiate a proinflammatory vascular response, recruit T cells, modify the lipid metabolism, and promote a proliferative phenotype of the vasculature, as shown here."

C. pneumoniae and platelet activity

Evidence that Chlamydia pneumoniae affects platelet activity in patients with acute myocardial infarction and ST-segment elevations. P Jaremo. Scand J Infect Dis 2001;33(10):747-748. "The pathogen appears to contribute to platelet responses occurring during myocardial infarctions with ST-segment elevations. It is concluded that an ongoing reactivation of a chronic infection is related to increased platelet activity."

C Pneumonia infection and social class

Epidemiology of Chlamydia pneumoniae infection in a randomly selected population in a developed country. C O'Neill, LJ Murray, GM Ong, DP O'Reilly, AE Evans, KB Bamford. Epidemiol Infect 1999 Feb;122(1):111-116.

C pneumoniae and other infections in lab animals

A new and larger study confirms and strengthens the original study by Fong et al (Rabbit model for Chlamydia pneumoniae infection. J Clin Microbiol 1997;35:48-52), showing that C pneumoniae causes atherosclerosis in rabbits fed a noncholesterol diet: De novo induction of atherosclerosis by Chlamydia pneumoniae in a rabbit model. IW Fong, B Chiu, E Viira, D Jang, JB Mahoney. Infect Immun 1999 Nov;67(11):6048-6055.

These lesions had fewer foam cells than the lesions induced in the cholesterol-fed rabbits: "Whereas the 0.5% cholesterol-fed rabbit type IV lesions closely resemble Stary's type IV lesion, with a lipid core and fibrous cap, the infected-rabbit advanced lesions were more fibromuscular, with calcification without a lipid core.

"It should be noted that the serum cholesterol level in the rabbits fed 0.5% cholesterol were 50-fold higher than those in the control rabbits and 10 times the recommended level for humans, whereas the serum cholesterol concentration in the 0.15% cholesterol diet falls within the recommended level for humans." They also observed that "There was no correlation with the mean antibody titer and development of atherosclerosis or periaortitis."

Effects of repeated Chlamydia pneumoniae inoculations on aortic lipid accumulation and inflammatory response in C57BL/6J mice. L Törmäkangas, L Erkkilä, T Korhonen, T Tiirola, A Bloigu, P Saikku, M Leinonen. Infect Immun 2005 Oct;73(10):6458-6466. "In conclusion, repeated inoculations increased aortic sinus lipid accumulation in normocholesterolemic mice. The correlation between the antibodies to mouse and chlamydial Hsp60 proteins and their association with lung inflammation further support the theory of the development of an autoimmune response against heat shock proteins after repeated chlamydial infections."

Antibiotic therapy

Antibiotics can eradicate bacteria if the dose and type of antibiotic are correct, and thus potentially reduce the risk of heart disease events. Most studies have shown beneficial effects. However, antibiotics don't work against viruses, which may complicate trials of antibiotics if viruses are a more important factor in the study population than bacteria.

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study. JB Muhlstein, JL Anderson, JF Carlquist, K Salunkhe, BD Home, RR Pearson, TJ Bunch, A Allen, S Trehan, C Nielson. Circulation 2000 Oct 10;102(15):1755-1760. 9 events versus 7 in the first 6 months, 13 versus 18 between 6 and 24 months, nonsignificant. "Unplanned coronary revascularization" a far less definitive endpoint than heart attack death) accounted for 19 of the 47 events. The study concluded that "antibiotic therapy with azithromycin is not associated with marked early reductions (>/= 50%) in ischemic events as suggested by an initial published report. However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed. Larger (several thousand patients), longer-term (>/= 3 to 5 years) antibiotic studies are therefore indicated."

Anti-germ theory spin-doctoring of the results in the mass media: "Setback for antibiotics as heart treatment," by Lawrence K. Altman. The New York Times 2000 Oct 10. Lead sentence: "Taking an antibiotic for three months failed to reduce the risk of new heart attacks and death among people with coronary artery heart disease, a Utah study has found." Muhlstein et al were also incorrect to say that their findings were consistent with only three possibilities: That C. pneumoniae does not cause coronary artery disease, azithromycin produces only a small benefit, or C. pneumoniae causes coronary artery disease but the wrong antibiotic was used. As noted, CMV has also been found to cause CAD.

(News) Antibiotics cut risk of cardiac death even in patients without H. pylori. Reuters Health 2000 Nov 29. id 30636 / Medscape. Re: A Stone et al. A randomized study with only one week course of 3 antibiotic regimens versus placebo reduced cardiac endpoints by 15% at one year.

Prevalence of Helicobacter pylori infection in coronary artery disease and effect of its eradication on coronary lumen reduction after percutaneous coronary angioplasty. M Kowalski, PC Konturek, P Pieniazek, E Karczewska, A Kluczka, R Grove, W Kranig, R Nasseri, J Thale, EG Hahn, SJ Konturek. Dig Liver Dis 2001 Apr;33(3):222-229.

Inflammation, infection and antimicrobial therapy in coronary heart disease - where do we currently stand? J Ngeh, S Gupta. Fundam Clin Pharmacol 2001 Apr;15(2):85-93. "Evidence from seroepidemiology, pathology, animal models, molecular biology and immunology, and human antibiotic intervention studies, collectively have suggested a largely positive association between C. pneumoniae infection and CHD." Too bad they buy into the "traditional risk factors" without challenging confounding by infection.

Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomized, double-blind, placebo-controlled trial. F Neumann, A Kastrati, T Miethke, G Pogatsa-Murray, J Mehilli, C Valina, N Jogethaei, CP da Costa, H Wagner, A Schomig. Lancet 2001 Jun 30;357(9274):2085-2089. "We showed a significant interaction between treatment and C pneumoniae antibody titre, favoring roxithromycin at high titres (adjusted odds ratios at a titre of 1/512 were 0.44 90.19-1.06) and 0.32 (0.13-0.81), respectively."

Treating cardiovascular disease with antimicrobial agents: a survey of knowledge, attitudes, and practices among physicians in the United States. F Gimenez-Sanchez, JC Butler, DB Jernigan, LJ Strausbaugh, CC Slemp, MJ Perilla, SF Dowell. Clin Infect Dis 2001 Jul 15;33(2):171-176.

(news) Antibiotics post acute coronary syndromes reduces risk of second attacks. E Susman, DG News 2001 Sep 3. Re JC Kaski at the 23rd Congress of the European Society of Cardiology.

Antibiotics against Chlamydia pneumoniae and prognosis after acute myocardial infarction. L Pilote, L Green, L Joseph, H Richard, MJ Eisenberg. Am Heart J 2002 Feb;143(2):294-300. "Exposure to antichlamydial antibiotics during the 3 months after AMI is associated with a small survival benefit, whereas exposure during the 6 months before AMI does not affect survival." However, the antichlamydial group was better off at two years.

Secondary prevention of atherosclerosis through chlamydia pneumoniae eradication (SPACE Trial): a randomised clinical trial in patients with peripheral arterial disease. T Vainas, FR Stassen, GW Schurink, TH Tordoir, RJ Welten, LH van den Akker, HA Kurvers, CA Bruggeman, PJ Kitslaar. Eur J Vasc Endovasc Surg 2005 Apr;29(4):403-411. 509 PAD-patients randomised to receive either a 3-day course of azithromycin (500 mg daily) or placebo, with 2 years of follow-up. 131 complications in the azithromycin group vs. 121 in the placebo group; 98 (38%) in the azithromycin vs. 84 (33%) in the placebo group.

The failure of antibiotics to prevent heart attacks (editorial). D. Taylor-Robinson, J Boman. BMJ 2005 Aug 13;331(7513):361-362. "In this context, it is a sobering thought that the role of Treponema pallidum in tertiary syphilis is not questioned despite the fact that antibiotic therapy does not alter the pathological changes at the late stage of disease."

Comparison of risks of infection versus dietary fat reduction

In a meta-analysis (Coronary heart disease, Helicobacter pylori, dental disease, Chlamydia pneumoniae, and cytomegalovirus: Meta-analysis of prospective studies. Am Heart J 1999;138:S434-S437), J Danesh reported a combined risk ratio for antibodies to C pneumoniae at baseline and CHD of 1.22 (0.96-1.54). However, the weighted mean age at baseline was 59 years, which reduces the association. And the outcomes of interest were heart attacks or coronary deaths, in which additional factors are involved besides those which cause atherosclerosis.

Plus, the obligatory ritual of "adjusting" for such things as smoking and social class may weaken the association when infection is the true cause of the purported risks. But the obvious fact never seems to occur to the perpetrators that social class or any of its proxy indicators by themselves do not cause heart disease or cancer, etc. And when it is proclaimed that these pretended risks are "independent," this is a clue to thinking people that there is something wrong with those statistics. The very existence of supposed risks associated with flagrantly non-causal indices of socioeconomic class is proof that the real cause(s) and/or exposure to them have not been properly identified.

Danesh's meta-analysis found a very similar risk ratio for dental disease, 1.24 (1.10-1.38). As with Chlamydia pneumoniae, there are very plausible biological reasons to believe that the infections which cause dental disease are also responsible for cardiovascular disease. These reasons are far superior to Danesh's claim that "The crude markers of oral hygiene used in these studies are probably also indicators of social class," meaning that we're supposed adjust them away simply because it's possible to do so; and presto! we shall be enlightened that heart disease is really caused by things like the lack of a high school diploma, instead of by infectious pathogens.

In comparison with the supposedly weak risks for infection, a new meta-analysis of dietary fat intake found no benefits at all from that approach. "Reducing dietary fat has little effect on cardiovascular disease. Half a century ago it was suggested that dietary fat causes heart disease and that reducing or modifying dietary fat intake will keep us healthy. This theory is still a mainstay of population "healthy eating" strategies and individual risk reduction advice. On p 757 Hooper et al present a systematic review of randomized controlled trials of dietary fat reduction or modification (including 40 intervention arms, 1430 deaths, and 1216 cardiovascular events). The review shows only modest reductions in cardiovascular events in those remaining on diet for over two years. The authors found little evidence for optimal intakes of total or individual fats." (From "This Week in BMJ," Re: "Dietary fat intake and prevention of cardiovascular disease: systematic review. L Hooper, CD Summerbell, JPT Higgins, RL Thompson, NE Capps, GD Smith, RA Riemersma, S Ebrahim. BMJ 2001 Mar 31;322(7289):757-763). And, there is still the likelihood that those in higher socioeconomic groups, with less exposure to pathogens, are more likely to remain on such diets for more than two years and thus bias the results.

Nutrition. The soft science of dietary fat. Gary Taubes. Science 2001 Mar 30;291(5513):2536-2545.

Danesh et al.'s latest study reports an odds ratio of 1.84 (1.40-2.43) for "incident coronary heart disease," not defined in the abstract; which they dismiss as not predictive. (Chlamydia pneumoniae IgA titres and coronary heart disease. Prospective study and meta-analysis. J Danesh, P Whincup, S Lewington, M Walker, L Lennon, A Thomson, Y Wong, X Zhou, M Ward. Eur Heart J 2002 Mar 1;23(5):371-375.)

Inflammation & CVD

New England Journal of Medicine editorial by Daniel J. Rader, MD, "Inflammatory Markers of Coronary Risk" (NEJM 2000 Oct 19;343(16):1179-1182), re two new studies demonstrating this risk. "The past decade has been characterized by growing interest in the idea that atherosclerosis is an inflammatory disease...." However, they still dance around the subject of infection as the root cause of this inflammation, and cling to confounded studies that blame smoking.

Acute-phase proteins and Chlamydia pneumoniae infection: which one is more important in acute coronary syndrome? H Song, H Tasaki, A Yashiro, K Yamashita, H Taniguchi, Y Nakashima. Jpn Circ J 2001 Oct;65(10):853-857. Indicates that acute-phase proteins may contribute more to acute coronaries.

Parameters of inflammation and infection in a community based case-control study of coronary heart disease. J De Backer, R Mak, D De Bacquer, L Van Renterghem, E Verbraekel, M Kornitzer, G De Backer. Atherosclerosis 2002 Feb;160(2):457-463. Found that "CRP levels are significantly different from controls, independent of known risk factors." Abstract does not state which antibodies were measured.

C-reactive protein and carotid intimal medial thickness in a community population. M Sitzer, HS Markus, MA Mendall, R Liehr, U Knorr, H Steinmetz. J Cardiovasc Risk 2002 Apr;9(2):97-103.

Relation of C-reactive protein levels to presence, extent and severity of of angiographic coronary artery disease. J Auer, M Rammer, R Berent, T Weber, E Lassnig, B Eber. Indian Heart J 2002 May-Jun;54(3):284-288.

Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. PM Ridker, N Rifai, L Rose, JE Buring, NR Cook. NEJM 2002 Nov 14;347(20):1557-1565. "Conclusions These data suggest that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score." But even this is an obfuscation, because infection causes elevated CRP levels; and the vaunted Framingham risk scores are worthless trash because they were developed using defective studies that ignored the role of infection, on purpose, in order to propagandize for the preordained conclusion that lifestyles are of key importance.

C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. J Danesh, JG Wheeler, GM Hirschfield, S Eda, G Eiriksdottir, A Rumley, GDO Lowe, MB Pepys, V Gudnason. NEJM 2004 Apr 1;350(14):1387-1397. CrP 1.45 (1.25-1.68) top third versus bottom third.

Fatality of future coronary events is related to inflammation-sensitive plasma proteins: a population-based prospective cohort study. G Engstrom, B Hedblad, L Stavenow, P Tyden, P Lind, L Janzon, F Lindgarde. Circulation 2004 Jul 6;110(1):27-31.
"Five inflammation-sensitive plasma proteins (ISPs; fibrinogen, orosomucoid, 1-antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 apparently healthy men, 680 of whom had a first coronary event [nonfatal myocardial infarction (MI) or death from coronary heart disease (CHD)] over a mean follow-up of 19 years.... Elevated ISPs, measured many years before the coronary events, were associated with a higher proportion of CHD deaths in the present study. If inflammation in unstable coronary plaque was the main cause for the relationships between elevated ISPs and fatal outcome, it could be assumed that the relationships would be strongest during the first years of follow-up. However, the relationship persisted after the exclusion of events that occurred during the first 10 years after the screening examination. The results show that the relation between elevated ISPs and an adverse outcome is not limited to the time at which clinical disease has been established."

Inflammatory markers and the risk of coronary heart disease in men and women. JK Pai, T Pischon, J Ma, JE Manson, SE Hankinson, K Joshipura, GC Curhan, N Rifai, CC Cannuscio, MJ Stampfer, EB Rimm. NEJM 2004 Dec 16;351(25):2599-2610. Nurses Health Study and Professionals Follow-Up Study. 1.79 (1.27-2.51) for levels >3.0 mg/l vs 1.0 mg/l.

Inflammation biomarkers and near-term death in older men. NS Jenny, ND Yanez, BM Psaty, LH Kuller, CH Hirsch, RP Tracy. Am J Epidemiol 2007 Mar 15;165(6):684-695. "In 5,828 Cardiovascular Health Study participants (United States, 1989-2000), 383 deaths (183 cardiovascular disease (CVD)) in years 1-3 (early) and 914 deaths (396 CVD) in years 4-8 (late) occurred. For men, when comparing highest to lowest quartiles, hazard ratios for early death were 4.1 (95% confidence interval (CI): 2.7, 6.3) for CRP and 4.1 (95% CI: 2.7, 6.4) for fibrinogen in models adjusted for CVD risk. For early CVD death, hazard ratios were 4.3 (95% CI: 2.2, 8.4) and 3.4 (95% CI: 1.8, 6.3), respectively. When comparing men in the highest quartiles of both biomarkers with those in the lowest, hazard ratios were 9.6 (95% CI: 4.3, 21.1) for early death and 13.5 (95% CI: 3.2, 56.5) for early CVD death. Associations were weaker for late deaths. For women, CRP (hazard ratio = 2.3, 95% CI: 1.4, 3.9), but not fibrinogen (hazard ratio = 1.3, 95% CI: 0.8, 2.2), was associated with early death. Results were similar for CVD death. Neither was associated with late deaths."

Other infections and CVD

cast 02-07-08