Risk Factors
Home Up Genetics & Biochem Risk Factors Prevention Treatment Heart Failure

 

Nine Factors Predict 90% of Heart Attacks: 

The INTERHEART case control study examined 15,152 individuals from 52 countries with their first heart attack and 14,820 others who did not have heart disease but who were of the same age, gender, and from the same city. The two most important risk factors were cigarette smoking and an abnormal ratio of blood lipids (Apolipoprotein B/Apolipoprotein A-1), which together predicted two-thirds of heart attack. Additional risk factors were high blood pressure, diabetes, abdominal obesity, depression, stress, a lack of daily consumption of fruits and vegetables, and a lack of daily exercise. Regular consumption of small amounts of alcohol was also found to be modestly protective. These nine predict more than 90% of the risk of a heart attack. Salim Yusuf, McMaster, Lancet 9/11/2004. 

Other risk factors include low thyroid levels, Cox-2 inhibitor and NSAID medication, fast heart beat, fewer teeth, periodontitis, too little or too much sleep, a history of various infections including herpes and cytomegalovirus, rheumatoid arthritis, a diet of meat, milk, butter, pastries, high homocysteine levels, soft water, fewer than two glasses of water a day, loss of height, lack of breastfeeding by a woman, and salt.

Factors associated with fewer heart attacks include drinking up to one alcoholic drink per day, flu shots, higher bilirubin, fluoride, fish, whole grains, legumes, breastfeeding for two years or more, and canola or olive oil.

 

ACAT-2 Liver Enzyme Stimulates Atherosclerosis: By "fooling" the liver into operating as if cholesterol levels were low, ACAT-2 accelerated the production of fat molecules known as VLDL, or the worst type of "bad cholesterol," which lead to the buildup of atherosclerotic plaque. Present in kidney failure in rats. ACAT-2, which normally takes cholesterol and stores it in specialized liver cells, was much more active in cases of kidney failure. Removing the cholesterol induced the liver to sense, falsely, that cholesterol counts were too low and produce high levels of heart disease-causing lipids. Very high VLDL. Kidney failure is another contributor to the high rates of heart disease. About 20 million Americans are suspected of having some degree of kidney failure. Amer J Physiology - Endocrinology and Metabolism. Nick Vaziri, UC Irvine Medical Center

ADMA, Marker of Endotheliol Dysfunction, a Heart Attack Risk Factor: In a prospective nested case-control study in 150 middle-aged non-smoking men from Eastern Finland, those who were in the highest quartile for serum ADMA (>0.62micromol/l) had a 3.9-fold (P=0.02) increase in risk of acute coronary events compared with other quartiles. In an 8-week 48-patient DB PC study, plasma ADMA concentrations remained unchanged in simvastatin 80mg/d, atorvastatin 40mg/d and placebo groups. Atheroscler Suppl. 2003 Dec;4(4):19-22. ADMA also risk factor in Japan study. It mediates endothelial dysfunction in HTN, DM, and heart disease. Pharmacol Rep 2006;58 Suppl:16-20.

Albumin: Increased Urinary Albumin a Cardiovascular and General Mortality Risk Factor: Circ 10/1/02. 40,500 Dutch adults were followed for 3 years. A doubling of urinary albumin was linked to a 29% increase in cardiovascular mortality (RR 1.29) and 12% overall (RR 1.12). BP lowering meds lower albumin excretion, especially ACE inhibitors.

A1C Hemoglobin Increase Linked to Increased Heart Disease: An English study of 10,232 adults ages 45-79 followed for 6 years found that for each 1% increase in the level of glycosylated hemoglobin or hemoglobin A1C, there was a 21% increase in cardiovascular problems.  Normal A1C is under 7% with most people ranging between 5% and 7%. Most diabetics have levels over 7%. A1C reflects a person's average blood sugar for the past 2-3 months.  K Khaw, Univ. Cambridge, Ann Int Med 9/21/04

A1C: Glycosylated Hemoglobin Risk Factor: Not just in DM but in a general population study of 4,662 followed for 4 years in England found HbA1c accounted for a 2.2 fold increase in DM death in men. In non-DM, HbA1c under 5% best and 1% increase linked with 28% increase in death from all causes. Glycosylated Hb is a more accurate estimate of glycemia over previous 6-12 weeks. However, research with DM finds lowering HBA1c with tight control little benefit for CVD but does help microvascular disease in retina and kidneys. Treatment of high blood pressure and cholesterol is much more important. BMJ 1/6/01

Anger Hurts: In study of 376 adults 18-30, those with hostility characterized by a cynical view of the world and aggressive responses to stressful situations were 2 ½ times more likely than less hostile to have calcium deposits in coronary arteries and 9 times as likely have enough calcium to indicate beginnings of fatty plaques. Carlos Iribarren, Kaiser Permanente, Sci News 4/17/99; Many studies have found this.

Apolipoprotein(a) in Smaller Versions Promote More Heart Disease: Apolipoprotein(a) is the protein component of low-density lipoprotein(a). Individuals inheriting smaller versions were more likely to have more heart disease with the harm greatest among the obese. A study of 715 Italians found that  Relationship between apolipoprotein(a) size polymorphism and coronary heart disease in overweight subjects Enzo Emanuele, Emmanouil Peros. Piercarlo Minoretti, Columba Falcone, Angela D'Angelo, Lorenza Montagna and Diego Geroldi. BMC Cardiovascular Disorders 12/12/03

B-Natriuretic Hormone Measures Heart Failure: A multicentric study of 1,600 patients found a 15 minute ER test correctly detected heart failure in 90%. B-type natriuretic peptide (BNP). The hormone is released by the heart ventricles when pressure rises, signaling a failing heart. San Diego VA, NEJM 7/18/02. It is useful in patients with chest pain or other inconclusive symptoms.

B-Natriuretic Hormone Predicts Death: in a study of 4,266 patients admitted with heart problems, and followed for 2 years, patients with BNP over 80 picograms/ml on admission and at 4 months, were 3 times as likely to die. David Morrow, Harvard, JAMA 12/14/05. 

Baldness in Vertex Bad: Physicians’ Health Study found mild, mod, and severe vertex balding with RR 1.23, 1.32, and 1.36 for heart disease and it was still a factor even after controlling for many factors (alcohol, DM, exercise, smoking, HBP, cholesterol, age, BMI, family history), but especially bad if there was high cholesterol or high blood pressure.

Baldness and Gray Hair Not Bad: In Copenhagen study of 20,000 with a 16 year follow-up, there was no association with mortality was found for gray hair or baldness or facial wrinkles for either sex except that a small group of men with no gray hair lived slightly longer (RR=.81). J Gerontol A Biol Sci Med Sci 1998 Sep;53(5):M347-50. An earlier analysis of the Copenhagen data after 12 years found some evidence of harm. No harm from gray also found in Med Hypotheses 1991 Dec;36(4):404-11

Bilirubin Anti-Oxidant: Traditionally, glutathione thought most powerful body anti-oxidant. Now its bilirubin. Slightly elevated bilirubin levels are linked to better alertness in newborns, a lower risk of coronary artery disease and cancer in adults, and less damage from stroke in animal models.

Breastfeeding The massive Harvard Nurses Study following 96,648 female nurses for 16 years found that after correction for other factors those who had spent at least two years breastfeeding were 19% less likely to suffer a heart attack than those who hadn't breastfed at all. Steube A, et al. 2/10/07 Society for Maternal-Fetal Medicine annual meeting.  The lead author speculated that breastfeeding helps to get rid of excess fat and fatty aicds stored up during pregnancy.  

C3F and Fibrinogen Early Signs of Heart Attack: C3f, was discovered as a heart attack marker for the first time and is known to be associated with inflammation. The other is a well-known protein called fibrinogen peptide A, which is involved in the clotting process. The presence of these proteins in the blood signals the beginning of a cascade of inflammatory and clotting events that eventually lead to a full-blown heart attack. The article is from a company making mass spectroscopy. It claims that elevation of these two is a very accurate predictor of heart attacks. It is supposedly 99% accurate and takes 5 minutes to do. Others troponin, creatinine kinase and myoglobin slower and less accurate. Marshall. Journal of Proteome Research 8/1/03

Celecoxib (Celebrex) Increased Death, Heart Attacks, Strokes, and Heart Failure: In a 3-year DB PC study of 2035 patients with a history of colorectal neoplasia given celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas, a composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (130% increase)(2.3%; HR = 2.3) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (240% increase)(3.4%; HR = 3.4). Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention. Solomon SD, McMurray JJ, et al. N Engl J Med. 2005 March 17. Ed: Even though Celebrex appears to have done worse than Vioxx, it has not been removed from the market.

Cholesterol: Very Low Said Best: In a very small study, 29 men and 4 women under age 44 with cholesterols of 146-195 were tested. Vessel dilation in high-normal group was half that of low-normal. Vessels’ ability to dilate declines as cholesterol goes up so as low as possible appears best. Helmut Steinberg, Indiana U, Circ 11/97

CMV Infection Risk Factor: 3,000 people, exposure to four common pathogens (disease-causing virus or bacteria) increased the risk of cardiovascular disease. The pathogens are CMV, Chlamydia pneumoniae (respiratory infections), Helicobacter pylori (ulcers), and hepatitis A (liver disease). The researchers found that CMV exposure carried a higher risk for cardiovascular events or death, while the other pathogens, by themselves, were not related to increased risk. However, they also found that a person's "total pathogen score" predicted a small increase in risk for cardiovascular events. Thus, people exposed to all four pathogens had a higher risk . CP IgG was detected in 82.9 percent of participants and IgA was found in 63 percent. Researchers found that 61.7 percent of the participants had antibodies for Helicobacter pylori, 76 percent for hepatitis A and 70.4 percent had them for CMV. CMV, which increased the risk of heart attack, stroke or cardiovascular death by about 24 percent. McMasters, Circulation 12/24/02

Cp-HSP60 More Sensitive Than CRP: 99% (217) of ACS patients were positive for Cp-HSP60, while only 20% stable angina patients were positive and no controls. CRP – a marker of inflammation recently linked with heart disease – elevated in 60% of acute coronary, 25% of stable angina patients and 8% of healthy persons. Biasucci Catholic U, Rome. Circulation 6/10/03

CRP=C-Reactive Protein Causes Damage: c-reactive protein, is just as important as monitoring cholesterol levels to prevent and treat heart disease and other ills, including stroke, sudden death and peripheral vascular disease. Now, UC Davis physicians have discovered that this protein is not just a marker for heart disease, but that it actually damages the blood vessel wall by blocking a critical "protector" protein and by promoting plaque formation. c-reactive protein decreases the stability of eNOS messenger RNA and prevents the activation of its second-messenger molecule, cyclic GMP. These events prevent eNOS from producing its protective biological effects. C-reactive protein also promotes white-blood-cell binding to blood vessel walls and stimulates the release of other adhesion molecules, including intercellular adhesion molecule 1, or 1CAM-1, and vascular cell adhesion molecule, or VCAM-1, which further promote plaque build-up. High risk groups include postmenopausal women and individuals with a positive family history of premature heart disease, hypertension, smoking or metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the "good" kind of cholesterol. Testing would be beneficial to individuals in these groups. Jialal, UCDavis, Circ 9/17/02

CRP Predicts Heart Attack, Stroke, Diabetes: High-sensitivity C-reactive protein (hsCRP) testing is inexpensive with reimbursement between $12-16. 50% of heart attack and stroke patients have normal cholesterols and hsCRP helps identify many of them. CRP is increased in obesity, autoimmune disease, by hereditary factors, lack of exercise, and smoking. CRP is elevated in Alzheiimer’s Disease, but it may not be a predictive factor. Aspirin lowers high CRP levels. Statins also lower CRP as does low-dose alcohol (up to one drink a day).

CRP: Risk Increased If High: In an 8-year follow-up, men with persistently elevated levels of antibodies to C pneumoniae or hHsp60 had about twice the risk of having a fatal or non-fatal heart attack than those with low levels of C pneumoniae and hHsp60 antibodies. With C pneumoniae and hHsp60 antibodies, risk was much higher when CRP level was also elevated. Men with persistently elevated CRP and C pneumoniae antibody levels had more than four times higher risk for coronary events than men with normal CRP and C pneumoniae antibody levels, Huittinen-Sävykoski says. The risk was similar for those with elevated CRP and hHsp60 antibody levels. The risk was highest when all three factors were elevated. "Almost everybody gets infected with C pneumoniae at least once during their lifetime and reinfections are also common. Circ 5/13/03

Dental: Fewer Teeth, Gingivitis Much More Common in Heart Patients: A study comparing 256 NYHA class II-IV heart disease patients and 250 matched controls found many more heart disease patients without teeth (35% vs. 15%) and many fewer teeth in those who had them (8.6 vs. 17).  Gingivitis was 237% more common in heart patients.  Dental infections and serum inflammatory markers in patients with and without severe heart disease. Meurman JH, Janket SJ, Qvarnstrom M, Nuutinen P. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Dec;96(6):695-700; However, among patients who already have heart disease, having gingivitis or periodontitis did not increase the risk of another heart attack. J Dent Res. 2002 Mar;81(3):186-91

Dental: Gingivitis, Periodontitis Not Heart Risk Factor in U.S. Study: In the 9 year follow-up of 8032 dentate adults ages 25 to 74 in the NHNESE study with no reported history of cardiovascular disease, including 1859 individuals with periodontitis, 2421 with gingivitis, and 3752 with healthy periodontal tissues, 1265 individuals developed heart disease, including 468 heart disease deaths. After adjustment for known cardiovascular risk factors, gingivitis was not associated with coronary heart disease (hazard ratio, 1.05), while periodontitis was associated with a nonsignificant increased risk (hazard ratio, 1.14). JAMA. 2000;284:1406-1410.

Dental: Gingivitis, Periodontitis Are Heart Risk Factors in Canadian Study: In a 22 year follow-up of over 11,000 Canadian adults initially without heart disease, adjusted for age, sex, diabetes status, serum total cholesterol, smoking, hypertensive status, and province, there was a statistically significant association between periodontal disease and risk of fatal coronary heart disease. Rate ratios (RR) of 2.15 and 1.90 were observed for severe gingivitis and edentulous status, respectively. Non-statistically significantly increased RRs of 1.81 and 1.63 were observed for severe gingivitis and edentulous status for cerebrovascular disease. Periodontal disease and risk of fatal coronary heart and cerebrovascular diseases. Morrison HI, Ellison LF, Taylor GW. J Cardiovasc Risk. 1999 Feb;6(1):7-11

Depression Risk Factor for Heart Attacks: In a 40-year follow-up of 1190 male medical students, the cumulative incidence of clinical depression was 12%. In multivariate analysis, the men who reported clinical depression were at significantly greater risk for subsequent coronary heart disease (RR, 2.12) and myocardial infarction (RR, 2.12). The increased risk associated with clinical depression was present even for myocardial infarctions occurring 10 years after the onset of the first depressive episode (RR, 2.1). Depression is a risk factor for coronary artery disease in men: the precursors study. Ford DE, Mead LA, Chang PP, Cooper-Patrick L, Wang NY, Klag MJ. Johns Hopkins. Arch Intern Med. 1998 Jul 13;158(13):1422-6.

Diet Compliance Poor After Heart Attack: American Journal of Health Promotion Aug 03 reports 118 pt after 2 years 87% claimed to be avoiding high fat intake but only 23% were consuming adequate amounts of fruits and vegetables despite being well trained in hospital.

Ear Lobe Crease in Relation to CAD Unclear: In a study of 1,048 Australians with DM, a diagonal ear lobe crease (ELC), Frank’s Sign, was more common with CAD P<.02. But those with ELC more likely male, older, and HBP (P<.02). After adjusting for known risk factors, ELC no longer predictive (P<.45). Aust N Z J Med 2000 Oct;30(5):573-7. In a Malay study, 31% males and 3% females in healthy population with ELC. A German study found no value to sign in patients undergoing coronary artery study. 670 patients, the greatest collective so far undergoing coronary angiography, were investigated prospectively with respect to the correlation between ELC and a hemodynamically relevant CHD (coronary diameter stenosis > 70%). In presence of ELC, CHD was observed in 55.0%, in its absence in 55.9%. . ELC highly predictive of age, to a lesser extent of obesity and hyperuricemia, but not of CAD. Z Kardiol 1995 Jul;84(7):512-9. In an Irish study of 125 patients undergoing coronary angiography, no association was found between CAD and ELC. Cardiology 1989;76(4):293-8. Another study of 100 with aortic stenosis found little value to the sign. Clin Cardiol 1986 Aug;9(8):388-90. However, an older study of 1000 unselected patients found high correlation between crease and angiographic CAD. It reported that ELC was independent of age. Am J Med 1983 Dec;75(6):1024-32. Study of 421 with and 421 without ELC found an increase in CAD P<.05. ELC was associated with tears in elastic fibers and thickened arterioles in all 12 biopsied ears. J Am Geriatr Soc 1980 Apr;28(4):184-7

Exercise Lowers CRP, Fibrinogen, WBC; Raises Albumin: 13,700 in NHANES III Survey showed markedly lower risk for elevated CRP in individuals engaging in vigorous exercise (OR 0.53). mounting evidence that physical activity may reduce inflammation, which is a critical process in the pathogenesis of cardiovascular disease. Epidemiology 2002 Sep;13(5):561-8. Fibrinogen was directly related to age, body mass index (BMI) and female gender and inversely to alcohol and moderate-heavy physical activity practice. Eur J Epidemiol 2001;17(10):953-8

Exercise: Lack of Exercise Capacity and Poor Heart Rate Recovery Markedly Increases Risk of Heart Death: A 20 year follow-up study of 3,000 women ages 30-80 found Among women with low risk Framingham scores, those with below median levels of both exercise capacity and HRR had significantly increased risk compared with women who had above median levels of these 2 exercise variables, 44.5 and 3.5 cardiovascular deaths per 10 000 person-years, respectively (hazard ratio for cardiovascular death, 12.93; 95% CI, 5.62-29.73; P<.001). Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study. Mora S, Redberg RF, Cui Y, Whiteman MK, Flaws JA, Sharrett AR, Blumenthal RS. JAMA. 2003 Sep 24;290(12):1600-7

Fibrinogen a Risk Factor: Fibrinogen is a marker for inflammation and also increases clotting. Higher fibrinogen, still within the normal range, is predictive of primary and repeat CVD. J Mal Vasc 2002 Jun;27(3):143-56. Exercise decreases both fibrinogen and CRP. Epidemiology 2002 Sep;13(5):561-8. Phlebotomy also lowers fibrinogen (see under "Iron" below in this section). Fibrinogen (Fib) plays an important role in platelet aggregation and thrombus formation, and homocysteine (tHcy) causes endothelial dysfunction and injury. Conjoint elevation of Fib and tHcy increased the risk of death by approximately 3-fold in three years. Although no significant interaction between Fib and tHcy was demonstrated, both provided independent information after adjustment for traditional risk factors. Arterioscler Thromb Vasc Biol 2002 Jun 1;22(6):1042-5.

Glycemic Index of Diet Not Important: Our findings do not support the hypothesis that a high-glycemic-index diet unfavorably affects metabolic risk factors or increases risk for CHD in elderly men without a history of diabetes or CHD. Zutphen Study. Eur J Clin Nutr 2000 Sep;54(9):726-31

Glycemic Index: Foods with High Index Lower HDL: Corn flakes, baked potatoes, instant rice have highest index (120), white and wholemeal bread (100), white rice, sugar (80-90), and beans, milk (40) with apples (50). Those lower glycemic index foods raise HDL. The index was positively assoc with CHD in the Nurses’ Health Study and in the Frost British study of 1420 adults. Therefore, lots of beans are good. Lancet ’99;353:1029. 

Heart Rate Recovery Predicts Death: Michael S. Lauer, Cleveland Clinic. HRR is not a reflection of underlying CAD and that it is an independent marker for mortality risk. 3000 consecutive patients exercise testing for suspected CAD. Coronary angiogram was performed within 90 days of exercise testing. Abnormal HRR was defined as a drop in heart rate of 12 beats or less in the first minute after exercise was completed. For patients who underwent stress echocardiography, a threshold of 18 beats or less was used. Nearly 30% of patients had abnormal HRR, yet only 14% had severe CAD on angiography. 11% died in 6 yr f/u.. On multivariate analysis, abnormal HRR and severe CAD were associated with a 60% and 40% increase, respectively, in the risk of death. J Am Coll Cardiol 2003;42:831-841 ‘03

Herpes Bad: In a study of 600 74-year-olds found 80% had antibodies to herpes, CMV, and chlmydia but in this study only herpes clearly linked with a doubling in heart attacks. Circulation 11/00. In patients given clot-busters, those with higher WBCs have higher risk of dying.

Height Loss Linked to Increased Death: In a 20 year follow-up of 4,200 British men, initially 40-50 years of age, the 1400 who lost more than 2 cm in height had an increased risk of death after controlling for other factors. Those who lost 3 cm in height were 64% more likely to die than those who lost less than 1 cm. Many of the additional deaths were due to cardiovascular disease, respiratory disease or other non-cancer diseases. Height loss was associated with a 42% increased risk of coronary events such as heart attacks, even in men who had no history of cardiovascular disease. Osteoporosis is already known to increase the risk of death. Goya Wannamethee, et al. Royal Free and University College Medical School, London. Arch Int Med 12/11/06.

Homocysteine 10% of Risk: 20 case-control and cross-sectional studies with 15000 pt. Meta-analysis reports that 10% of risk of CAD due to homocysteine. JAMA ’95 274:1049-57. However, two new meta-analyses confirm that a raised level of blood homocysteine is a risk factor for ischemic heart disease but find that the risk is lower than previously thought. Say routine screening for homocysteine levels and folate methylenetetrahydrofolate reductase (MTHFR) polymorphism not warranted. (JAMA 2002;288:2015-22, 2023-31).

IL-1 Gene Variations Linked to C-Reactive Protein: strong connection between common variations in IL-1 genes and CRP and other inflammatory proteins by the liver. Numerous studies have identified inflammation as a major component of the atherosclerosis disease process, the accumulation of fatty plaques in arteries that can lead to heart attack or stroke. CRP, a protein marker of inflammation, has recently been recognized as a significant factor in understanding cardiovascular disease. IL-1, a primary regulator of inflammation, wound healing and bone and connective tissue responses following injury or the onset of disease, starts the chain reaction of inflammatory proteins that leads to production of CRP. Mayo, Cytokine 5/20/02.

Income: High Income Protective: In a prospective national 3,617 adult sample with a 7.5 year follow-up, high education benefit was almost entirely reflected by strong tie to high income. The benefit was still strong after controlling for smoking, alcohol, weight, and sedentary lifestyle. The risk of dying in the lowest income after controlling for all above factors was RR 2.77 and in middle income was RR 2.14. Lantz, JAMA 7/98;279:1703

Income: Disadvantaged Lower Class for IHD Mortality Corrected in Part by Other Factors: In a Danish study of 6,000 healthy adults ages 53-74 with a 6 year follow-up, lower social classes IV-V when compared to the high social classes I-III had a death rate from ischemic heart disease increased by 44% (RR 1.44).  This was lowered by age, BP, smoking, lipids, physical activity to RR 1.38 and further lowered to RR 1.12 by correcting for low plasma selenium, exposure solder fumes, low leisure time physical activity in middle age, and abstinence or low consumption wine or spirits. Int J Epid ’97;26:516 

Infections Increase CVD: (Circulation 2002;105:15-21) Mainz University Clinic, Germany, looked at 572 patients cardiac catheterization. All the patients were tested for antibodies to several bacteria and viruses, including herpes simplex viruses 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori. Followed for an average of 3.2 years, over which time the extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle brachial pressure index. Patients who had four or five past infections were 1.8 times as likely to have advanced atherosclerosis as people with fewer infections. Patients with 6-8 past infections were 2.5 times as likely.

Inflammation Sensitive Proteins (ISPs) a Risk Factor for Heart Attacks: A Malmo University Hospital study of 6000 men ISPs: alpha1-antitrypsin, haptoglobin, ceruloplasmin, fibrinogen and orosomucoid, were analyzed. Of the original group, 1108 had no traditional cardiovascular risk factors and were deemed low risk. Over 18.1 years of follow-up, there were 227 heart attacks. The relative risk of MI was 1.0 in those with no ISPs which reached the highest levels. This rose to 1.9 for those with 1 ISP at the highest level, to 1.8 for 2 at that level and 2.9 for those with 3 or more at the highest level. Overall, in this group, the increased risk was seen only after 10 or more years of follow-up. Corresponding findings for age-adjusted relative risks in the high risk group were 1.0, 1.4, 1.9 and 2.0. Low-grade inflammation can be observed many years before a heart attack. Gunnar Engstrom, Arterioscler Thromb Vasc Biol 12/2003;23:2247-2251. 

Interleukin-6 Risk CHD Factor: Interleukin 6 also linked to MI with those with high levels at 3 times the risk. JAMA 11/7/01. Interleukin-6 polymorphisms at higher risk with increased IL-6 blood levels, e.g. –174G>C, while –174CC had a lowered risk if treated with pravastin; these patients had a greater decrease in LDL cholesterol. Arterioscler Thromb Vasc Biol 2002 Apr 1;22(4):599-604

Iron: Increased Stores Unfavorable: Men with low serum transferrin receptor concentration/serum ferritin ratio 2.9 and 2.0 times risk of acute MI compared to men in highest third. 99 Finnish men after a heart attack vs. 98 controls. Tuomainen, Univ. Kuipio, Circ 4/98;97:1461; Heme iron, supplemental iron, Vit C, and alcohol were all associated with increased iron and caffeine was associated with decreased iron stores measured by serum ferritin in Framingham elderly. Fleming, Tufts, Am J Clin Nutr 4/98;67:722; Increased LDL, apoB, and electrophoretic LDL were associated with increased iron stores. Measured by ferritin. Ferritin at 200-500 was a strong risk factor in Finnish.; Among elders, intakes of highly bioavailable forms of iron (supplemental iron and red meat) and of fruit, a dietary source of an enhancer of nonheme-iron absorption (vitamin C), promote high iron stores, whereas foods containing phytate (whole grains) decrease these stores. Individual dietary patterns may be important modulators of high iron stores. Am J Clin Nutr. 2002 Dec;76(6):1375-84

Iron: High Serum Iron in Elderly Good: In a study of 3,936 over age 70 followed for 4.4 years, researchers found the highest quartile in serum iron vs. the lowest had CAD death risk for males of only RR 0.22 and overall death risk of RR 0.68; females' CAD risk was RR 0.48. Corti, NIH, Am J Cardiol ’97;79:120

Iron: Iron Stores Not Related to Heart Disease and Only Possible Link to Stroke: 1,612 adults with long follow-up. Hazard Ratio for coronary heart disease of highest ferritin tertile to lowest 0.96. and for stroke 1.48. Serum ferritin and cardiovascular disease: a 17-year follow-up study in Busselton, Western Australia. Knuiman MW, Divitini ML, Olynyk JK, Cullen DJ, Bartholomew HC.

Iron: No Relationship with Coronary Arteriosclerosis: In larger study of patients undergoing angiography, 200 with and 200 without arteriosclerosis were compared. Serum levels of ferritin and of other organic iron indicators--transferrin saturation, total iron-binding capacity, hemoglobin and hematocrit--were neither risk factors nor risk markers for coronary atherosclerosis. Sao Paolo. Serum ferritin levels and other indicators of organic iron as risk factors or markers in coronary artery disease. Armaganijan D, Batlouni M. Rev Port Cardiol. 2003 Feb;22(2):185-9

Iron: Review of Iron Stores Says Unproved: Says 8 epidemiological studies found an association between CHD and iron stores and 18 did not. Meyer, Kansas, Clin Cardiol, 12/96;19:925

Reducing Iron by Phlebotomy Helps: At Near Iron Deficiency levels, caused by phlebotomy of 31 patients, a significant increase of HDL-cholesterol (p < 0.001) and reductions of blood pressure (p < 0.001), total and LDL-cholesterol (p < 0.001), triglyceride (p < 0.001), fibrinogen (p < 0.001) and glucose and insulin responses to oral glucose loading (p < 0.001) were noted, while homocysteine plasma concentration remained unchanged. These effects were largely reversed by a 6-month period of Fe repletion with reinstitution of Fe sufficiency. Thus, although individuals at high risk for ASCVD are not Fe-overloaded, they seem to benefit, metabolically and hemodynamically, from lowering of body Fe to levels commonly seen in premenopausal females. Ann N Y Acad Sci 2002 Jun;967:342-51

Leptin Levels Risk Factor: A 30% increase in blood leptin was linked to a 25% increase in heart attacks. Leptin reflects level of obesity and lower by exercise. C-reactive protein also increases with leptin levels. Circulation 12/18/01.

Lipo-protein (a) Risk Factor: An Lp(a) level exceeding 300 mg L-1 indicates a poor further prognosis and may help to identify patients who probably need powerful secondary prevention programs to improve their prognosis. 1216 coronary angiogram patients were followed for 6.7 years in Sweden. It is a known risk factor for arteriosclerosis. J Intern Med 2002 Jul;252(1):27-35; Lipoprotein(a) is an LDL particle with extra adhesive protein enabling attach to walls of vessels and increases plaque. Simple LDL lacks adhesiveness and little risk CVD. JAMA 8/96 high Lp(a) double risk MI before age 55.

Lp(a) a Male Risk Factor: Cardiovascular Health Study found Lp(a) lipoprotein, which increases atherothrombogenesis, also has an increased risk of vascular disease and death. Compared with those in the lowest quintile for Lp(a) lipoprotein, men in the highest quintile had three times the unadjusted risk of stroke (relative risk [RR], 3.00); more than twice the risk of vascular death (RR, 2.54), and almost twice the risk of death from all causes (RR, 1.76). Correcting for other risk factors did not change the relationship. Women were not affected. NEJM 11/28/03. 349:2108-2115

Meat, Milk, Butter Pastries Bad; Legumes, Oils, Vegetables, Alcohol Good: The Seven Country Study with 25 year follow-up of 12,763 middle-aged men belonging to 16 cohorts in seven countries (USA, Finland, The Netherlands, Italy, former Yugoslavia, Greece and Japan) with periodic evaluation found death rates from CHD showed large differences, ranging from 268 per 1000 in East Finland to 25 per 1000 in Crete, Greece. Butter (R = 0.887), meat (R = 0.645), pastries (R = 0.752), and milk (R = 0.600) consumption, and significant negative correlation coefficients for legumes (R = -0.822), oils (R = -0.571), and alcohol (R = -0.609) consumption. Combined vegetable foods (excluding alcohol) were inversely correlated (R = -0.519), whereas combined animal foods (excluding fish) were directly correlated (R = 0.798) with CHD death rates. Eur J Epidemiol 1999 Jul;15(6):507-15. Food intake patterns and 25-year mortality from coronary heart disease: cross-cultural correlations in the Seven Countries Study. The Seven Countries Study Research Group. Menotti A, Kromhout D, Blackburn H, Fidanza F, Buzina R, Nissinen A. U Minn.

MPO Myeloperoxidase Risk Factor: In a study of patients with the highest levels of MPO, or myeloperoxidase, which is normally found in infection-fighting white blood cells, had a 20-fold greater risk of heart disease than those with the lowest levels. High levels were even found in people with no significant heart disease and with no risk factors such as high cholesterol and high blood pressure. 333 patients. 50% heart attacks in patients with normal cholesterol. MPO better predictor of atherosclerosis than is cholesterol. Stanley Hazen, Cleveland Clinic.

Naproxen, But Not Ibuprofen May Be Safe: COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen. The studies included almost 140,000 patients and confirmed that, for patients taking Cox 2 inhibitors, there is an approximately 86 percent greater risk of heart attack than those who do not use the drug. However, the study also found that the risk of heart attack appeared to be equally high among patients who used ibuprofen. The increased heart attack risk was not seen with naproxen, however, which the authors suggest may be because this drug works a little differently than the others. Patricia Kearney et al. British Medical Journal June 2, 2006. 

Omega-3 Dramatically Reduces Sudden Death: In Harvard’s 17 year follow-up of 34,000 male medical professionals, sudden death due to heart disease was reduced in 3rd and 4th quartiles, i.e., highest blood omega-3 levels with RR of 0.28 and 0.19. NEJM 4/10/02

Orthostatic Hypotension CHD Risk Factor: In 6 years of follow-up on 12,433 adults with drop of 20 mm/Hg systolic or 10 diastolic at baseline found HR=1.85 after control for age, ethnicity, gender, and CVD risk factors. Am J Hypertension 2000;13:571

Periodontal Disease Increased Heart Disease: J Periodontol ’98;69:841-50; Clin Infect Dis ’98;26:719; Ann Periodontol ’98;3:127

Rheumatoid Arthritis Doubles Risk: Brigham and Women's Hospital analyzed health conditions of more than 114,000 people in a 20-year study, including 527 arthritis sufferers. Doubles heart attacks, triple if have had RA for 10 years. No effect on strokes. Circulation 2/27/03.

Rofecoxib (Vioxx) Increased Thrombotic Events: In a planned 3-year DB PC study of the effect of rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in 2,586 patients with a history of colorectal adenomas, 46 patients in the rofecoxib group had a confirmed thrombotic event during 3,059 patient-years of follow-up, as compared with 26 patients in the placebo group during 3,327 patient-years of follow-up, a 92% increase with rofecoxib; P=0.008). Overall and cardiovascular mortality was similar in the two groups. Conclusions Among patients with a history of colorectal adenomas, the use of rofecoxib was associated with an increased cardiovascular risk. Cardiovascular Events Associated with Rofecoxib in a Colorectal Adenoma Chemoprevention Trial. Bresalier RS, Sandler RS, et al. N Engl J Med. 2005 March 17. Ed: As everyone knows, Vioxx was pulled from the market shortly after this study.

Sed Rate a 20 Year Risk Factor: Margret B. Andresdottir, Icelandic Heart Association-Research Institute. 16,000 adults with baseline ESR followed for 20 years. For men, having a baseline ESR in the highest versus the lowest quintile raised the risk of heart disease by 57%, for women by 49%. These elevated risks remained stable for up to 25 years in men and 20 years in women. A higher ESR was also predictive of stroke mortality, but the association fell just short of statistical significance in both sexes. These findings support the evidence of an inflammatory process in atherosclerosis. Am J Epidemiol 2003;158:844-851.

Short Legs Bad: University of Bristol in southwest England. "Leg length is inversely associated with the risk of coronary heart disease and with components of the insulin resistance syndrome among adults," Professor George Smith told Reuters. 11/14/01

Sleep 7-8 Hours Least Heart Disease: Harvard study of nearly 72,000 nurses, 10 yr f/u. Women who averaged five hours or less of sleep a night were 39 percent more likely to develop heart disease than women who got eight hours. Those sleeping six hours a night had an 18 percent higher risk of developing blocked arteries than the eight-hour sleepers. And nine or more hours of shuteye was associated with a 37 percent higher risk of heart disease. Arch Internal Med 1/27/03

Tachycardia Early Indicator CHD: J Hypertens Suppl 1998 Jan;16(1):S9-15, Julius, U Mich. High heart rate precedes development of HBP and highly correlated with HBP. Good measure of heart work and heart stress. Predicts CHD and non-cardiovascular mortality. Good predictor of longevity. Strong risk factor sudden death and arrhythmia. Animals with high heart rate more plaque in coronaries. High heart rate a marker of high sympathetic tone and assoc with high insulin, insulin resistance, dyslipidemia, high hematocrit and excess weight.

Telomere Shortening Factor Lessened by Statin: Telomere lengths at recruitment in 484 individuals in the West of Scotland Primary Prevention Study (WOSCOPS) who went on to develop coronary heart disease events were compared with those from 1058 matched controls who remained event free. Mean telomere length decreased with age by 9% per decade (p=0.001) in controls; much the same trend was seen in cases (-5.9% per decade, p=0.1902). Individuals in the middle and the lowest tertiles of telomere length were more at risk of developing a coronary heart disease event than were individuals in the highest tertile (odds ratio [OR] for coronary heart disease: 1.51, p=0.0029 in the middle tertile; 1.44, p=0.0090 in the lowest). In placebo-treated patients, the risk of coronary heart disease was almost double in those in the lower two tertiles of telomere length compared with those in the highest tertile (1.93, p=0.0005 in the middle tertile; 1.94, p=0.0006 in the lowest). By contrast, in patients treated with pravastatin, the increased risk with shorter telomeres was substantially attenuated (1.12, p=0.5755 in the middle tertile; 1.02, p=0.9380 in the lowest). Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Brouilette SW, et al. University of Leicester, UK. Lancet 2007 Jan 13;369(9556):107-14.

Thrombomodulin Gene Abnormality Increased CHD in Blacks: Thrombomodulin dots the walls of blood vessels preventing unwelcome clotting. A one amino acid variation in some Afro-Americans increased heart disease six-fold. Circulation 4/24/01

Thyroid Disease: Mild Hypothyroidism May Raise Cardiac Risk: Of 1,055 women in the Rotterdam Study, 12% had untreated subclinical hypothyroidism: thyroid stimulating hormone (TSH) greater than 4.0 mU/L coupled with a normal concentration of free thyroxine. They had a significantly higher baseline prevalence of both aortic atherosclerosis (odds ratio, 1.9) and past heart attack (OR, 2.3). There was also a trend toward an increased five-year incidence of heart attack in women with subclinical disease (relative risk, 2.5). The data were adjusted for the participants’ age, body mass index, lipid levels, blood pressure, and smoking. All women aged 50 and older should be screened with a TSH test every two to five years. Some physicians think it’s unnecessary to treat subclinical disease because there’s no definitive evidence that doing so improves patients’ quality of life. Thyroid replacement is a relatively benign and does prevent progression to full hypothyroidism. Ann Intern Med. 2000;132:270-8.

Treadmill Induced Irregularity Good Predictor: decade-long study of more than 29,000 patients showed that the presence of irregular heartbeats in the minutes after a treadmill test is a better indicator of death within five years than irregular heartbeats during the test itself. Cleveland Clinic found that 11 percent of patients with irregular heartbeats after a stress test were dead within five years, compared with 5 percent of those who did not have such irregular rhythms. Nine percent of patients with irregular heartbeats during the test itself died within five years, compared with 5 percent who did not have irregular beats during the exercise. NEJM 2/27/03

Uric Acid Elevation Big Risk Factor: In a study of 316 angiography patients with coronary artery disease followed for 5 years, uric acid >/=5.2 mg/dl independently imparted a 3.5-fold increased risk (OR 3.5) for cardiovascular death and major clinical events over a 5-year period. Uric acid may be a contributing factor to the progression of atherosclerosis and its complications. Am J Nephrol. 2005 Feb 21;25(1):36-44

Uric Acid Increased by Meat; Reduced by Dairy: Using data from 14,809 adults in the Third National Health and Nutrition Examination Survey and adjusting for age, sex, total energy intake, body mass index, use of diuretics, beta-blockers, allopurinol, and uricosuric agents, self-reported hypertension and gout, serum creatinine level, and intake of alcohol, researchers found that the serum uric acid level increased with increasing total meat or seafood intake and decreased with increasing dairy intake. After adjusting for age, the differences in uric acid levels between the extreme quintiles of intake were 0.48 mg/dl for total meat, 0.16 mg/dl for seafood, and -0.21 mg/dl for total dairy intake. After adjusting for other covariates, the differences between the extreme quintiles were attenuated but remained significant (P < 0.05). The total protein intake was not associated with the serum uric acid level in multivariate analyses (P = 0.74 for trend). Milk 1 or more times per day had a lower serum uric acid level than did those who did not drink milk (multivariate difference -0.25; P < 0.001). Yogurt at least once every other day had a multivariate difference -0.26; P < 0.001. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Choi HK, Liu S, Curhan G. MGH-Harvard. Arthritis Rheum. 2005 Jan;52(1):283-9.

Uric Acid: Hyperuricemia induces arteriolopathy of preglomerular vessels, which impairs the autoregulatory response of afferent arterioles, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening produces severe renal hypoperfusion. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis, as well as arterial hypertension. Sanchez-Lozada LG, et al. Mexico City. Kidney Int. 2005 Jan;67(1):237-47.

Uric Acid Elevation Increased Stroke Risk in Taiwan: In an 11-year follow-up of 3602 adults older than 35 years, 86 develop coronary heart disease and 155 had strokes. The rate ratios of hyperuricemia ranged between 2.00 and 3.96, with higher risk ratios in women than in men. After adjustment for age effect, higher uric acid at baseline was associated with significant CHD risk in both genders (hazard risk [HR] 1.43 in men and HR 1.22 in women). But the magnitude of hazard risks decreased after adjusting more atherosclerotic risk factors for CHD. Multiple adjustment by risk factors demonstrated that uric acid was still a significant predictor for stroke in women (HR 1.32). Uric acid had significant risk only in hypertension and metabolic syndrome subgroups. Authors conclude that uric acid could predict cardiovascular events in the community of relatively low CHD but high stroke risk in Taiwan. Hyperuricemia as a risk factor on cardiovascular events in Taiwan: The Chin-Shan Community Cardiovascular Cohort Study. Chien KL, et al. National Taiwan University, Taipei, Taiwan. Atherosclerosis. 2005 Sep 7

Uric Acid Elevation After Heart Attack Predicts Heart Failure and Death: Serum uric acid (UA) levels reflect circulating xanthine oxidase activity and oxidative stress production. Hyperuricemia has been identified in patients who have congestive heart failure and is a marker of poor prognosis in such patients. Using the Japanese Acute Coronary Syndrome Study database of 1,124 patients hospitalized within 48 hours of a heart attack, there was a close relation between serum UA concentration and Killip's classification. Patients who developed short-term adverse events had high UA concentrations. The risk of death in the highest quartile of UA was 270% higher (HR = 3.7) compared with those in the lowest quartile after adjustment for independent factors that were related to mortality. The best UA cutoff for predicting survival is 447 micromol/L. Hyperuricemia after AMI is associated with the development of heart failure and death. Prognostic usefulness of serum uric acid after acute myocardial infarction (the Japanese Acute Coronary Syndrome Study). Kojima S, et al. Kumamoto University, Japan. . Am J Cardiol. 2005 Aug 15;96(4):489-95

Water Cuts Heart Attacks: Loma Linda University survey in 1976 with people 38 years and older Seventh-Day Adventist 8,280 men and 12,017 women followed for six years. 246 respondents died from heart disease. Reuters, Jacqueline Chan, the lead researcher, concluded that women who drank more than five 8-ounce glasses of water each day were 41 percent less likely to die from a heart attack during the study period than those who drank two or fewer glasses daily. For men who drank a lot of water, the heart attack risk dropped by 54 percent. Increased amounts of other beverages associated with 50% increased rate of heart attacks. Am J Epid 5/1/02.

Water Hardness Reduces Heart Attacks: Fluoride Good; Iron, Copper Bad: In a study of 19,000 Finnish men, calcium, magnesium, fluoride, iron, copper, zinc, nitrate and aluminum were measured in almost 12,500 groundwater samples. Higher fluoride levels were protective, with every one milligram of fluoride per liter of household drinking water was associated with a 3% decrease in the risk of a heart attack. But for every microgram of iron per liter, risk increased by an average of 4%, and for every microgram of copper per liter of water, it increased by 10%. Anne Kousa, J Epid Comm Health 1/15/04 

Work Stress Increases Heart Disease: 25.6 years follow-up of 812 adults in Finland found that after adjustment for age and sex, high job strain, a combination of high demands at work and low job control, had a 2.2-fold cardiovascular mortality risk compared with their colleagues with low job strain. Effort-reward imbalance (low salary, lack of social approval, and few career opportunities relative to efforts required at work) was 2.4 increased risk. These ratios remained significant after additional adjustment for occupational group and biological and behavioral risks at baseline. High job strain was associated with increased serum total cholesterol at the 5 year follow up. Effort-reward imbalance predicted increased body mass index at the 10 year follow up. BMJ 2002;325:857 ( 19 October ). Work stress and risk of cardiovascular mortality: prospective cohort study of industrial employees; Mika Kivimäki, Päivi Leino-Arjas, Ritva Luukkonen, Hilkka Riihimäki, Jussi Vahtera, Juhani Kirjonen.  Department of Psychology, University of Helsinki

Thomas E. Radecki, M.D., J.D.

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