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cardiovascular risk factor

Etiology: Risk factors: - male age >= 45 years - polymorphism (haplotype I) on the Y chromosome affecting differential expression of genes related to inflammation & immunity, increases risk 50% independent of other risk factors [59] - female age >= 55 years - hormonal deficiency a) estrogen (estradiol) deficiency (men & women) [19] - early menopause (before age 45) [141] b) androgen deprivation therapy - higher serum testosterone in postmenopausal women [168] - in contrast, higher serum estradiol in postmenopausal women associated with lower cardiovascular risk [168] - young nonsmokers without hypertension generally not at risk: - only 0.04% of women < 50 & 0.09% of men < 40 years with elevated risk [152] - black ethnicity - hispanics tend to be low risk - coronary artery disease [135] - family history of premature cardiovascular disease [1] - sibling history of cardiovascular disease [11] - children with cardiovascular risk factors are more likely to experience serious cardiovascular events in adulthood [181] - dyslipidemia* - elevated total serum cholesterol (>= 200 mg/dL) [1] - elevated LDL cholesterol (> 160 mg/dL) - type B LDL particles responsive to carbohydrate intake but not type A LDL particles reponsive to saturated fat intake implicated [86] - low HDL cholesterol (< 40 mg/dL), even with low LDL [22] - HDL cholesterol > 60 mg/dL allegedly compensates for one other cardiac risk factor [1] - elevated serum triglycerides [148] - serum triglycereides > 150 mg/dL in high-risk statin treated patientsassociated with increased cardiovascular risk [174] - elevated serum C-reactive protein (> 2 mg/L) - elevated plasma homocysteine# - smoking* [4a]; risk 25% greater in women than men [55] - smoking cessation is the single most important thing a smoker can do to improve life expectancy & quality of life [1] - risk reduced within 2 years of smoking cessation - risk returns to baseline 10 years after smoking cessation [1] - air pollution [136] - hypertension** a) BP > 140/90, prehypertension [12] or being treated for hypertension [1] b) systolic hypertension - systolic hypertension during sleep [26] - systolic blood pressure greater during sleep than when awake substantially increases risk associated with sleep deprivation [26] - systolic hypertension in adults < 50 years of age increases 30-year cardiovascular mortality [112] c) wide variability of blood pressure in hypertensive adults associated with increased cardiovascular risk [120] - variability in systolic BP (> 14 mm Hg) (RR=1.3-1.6) - variability in diastolic BP also associated with increased risk [120] - higher visit-to-visit variability in systolic BP is associated with increased risk of cardiovascular events in patients with systolic hypertension [160] d) high & low systolic blood pressure (> 140 mm Hg or < 120 mm Hg) & high & low diastolic blood pressure (> 80 mm Hg or < 70 mm Hg) associated with increased cardiovascular risk in patients with stable coronary artery disease [176] - no increase in risk of stroke with low blood pressure e) elevated blood pressure in young adults confers cardiovascular risk later in life [171] - psychosocial stress, anger, hostility (catecholamine release)* - blue collar & service workers (RR=1.4) [99] - police officers during stressful law enforcement duties [106] - job insecurity [83] - childhood psychosocial stress [129] - diabetes mellitus* (2-fold risk) a) dysglycemia or increased HgbA1c inconsistent risk factor [5,95] b) glycated hemoglobin better than fasting glucose for predicting cardiovascular risk in non-diabetic adults [40] c) microalbuminuria [1] d) risk greater for women than for men [94] e) metabolic syndrome (risk similar to diabetes alone) [43] f) severe hypoglycemia is a risk factor [46] g) elevated insulin h) hyperglycemia [148] i) diabetes mellitus less of a risk for cardiovascular events than coronary artery disease [135] j) much greater risk factor than hypertension or dyslipidemia [1] - obesity* or overweight a) increased BMI associated with increased risk - morbidly obese > obese > overweight [162] - overweight associated with increased cardiovascular morbidity, but not mortality [162] b) increased BMI, waist circumference or waist-to-hip ratio equally predictive of risk [53] c) waist-to-hip ratio might be better than BMI for predicting sudden cardiac death [108,127] d) duration of obesity factors into risk [78] - physical inactivity* - suboptimal intake of dietary factors (fruits, vegetables, whole grains, sodium, nuts & seeds, processed meats) accounted for 45.4% of U.S. cardiovascular mortality in 2012 - diet low in fruits & vegetables* [147] - high sodium intake (9.5%) - low consumption of nuts and seeds (8.5%) - high intake of processed meats (8.2%) [147] - constipation [189] - alcoholism, binge drinking* [1,50], alcohol abuse [145] - loneliness, social isolation associated with underlying risk factors, unhealthy lifestyles or poor mental health [164] - social isolation with independent component of cardiovascular risk [1] - elevated resting heart rate (either sex) - diminished heart rate variability - obstructive sleep apnea [80] - adequate CPAP may reduce risk [61] - non-coronary atherosclerosis [4] - chronic kidney disease, even early stages [1,45] - proteinuria [1] - any degree of albuminuria is associated with increased risk of cardiovascular events, heart failure hospitalizations, & all-cause mortality [1] - acute renal failure requiring renal dialysis - osteoporosis - chronic inflammatory diseases [113] - rheumatoid arthritis [13,113] - psoriatic arthritis [113] - psoriasis greater risk factor than diabetes mellitus type 2 [142] - persistent asthma [184] - lower level of education [15,153] - > 50% of adults who do not complete high school have an adverse cardiovascular event during their lifetime [153] - sleep deprivation & and altered circadian sleep rhythms may play role [25,26,37] - bedtime between 10 & 11 PM may be optimal time to reduce cardiovascular risk [179] - major depression & bipolar disorder [47,121] - infections - HIV1 infection [31,33,96] - shingles [89] - hospitalization for pneumonia in middle-aged & older adults - RR=4.1, risk greatest within 30 days) [111] - pneumococcal pneumonia or influenza infection - RR=5-12 in the week following infection) [167] - elevated plasma C-reactive protein [31] - elevated plasma FGF-23 [163] - radiation therapy [1] - migraine [88] - pharmaceutical agents: - rofecoxib (Vioxx), doclofenac [17,42] - dietary trans-fats [122] - high calcium intake in women > 1400 mg/day - calcium supplements further increase risk [74] - arsenic exposure (urine arsenic > 15 ug/g or creatinine) - abnormal electrocardiogram in the elderly [64] - ABO blood type: AB (1.23), B (1.15), & A (1.08), (risk relative to those with type O blood) [67] - extremes in temperature [68] a) U-shaped mortality vs temperature b) minimum mortality at 75 degrees c) hot temperatures confer higher mortality than cold temperatures d) extreme temperatures may act as a trigger for cardiovascular events due to changes in 1] blood pressure 2] blood viscosity 3] plasma cholesterol 4] heart rate - women's health factors - history of miscarriage or stillbirth [97,158] - menarche before age 12, menopause before age 47 [158] - endometriosis [130], hysterectomy [158] - preeclampsia [172] - increase in age at 1st birth associated with lower risk [158] * from MKSAP [1] - older age, male - modifiable - dyslipidemia, smoking, diabetes mellitus type 2, hypertension, obesity, inadequate exercise, poor diet [1] - smoking is the greatest modifiable risk factor [1,188] - diabetes mellitus much greater risk factor than hypertension or dyslipidemia - coronary artery calcium score > 300 (75%) - high-sensitivity CRP in serum > 2 mg/L - ankle brachial index < 0.9 - LDL cholesterol >= 160 mg/dL - family history of atherosclerotic cardiovascular disease in first degree relative < 55 years male, < 65 years female [2] - red meat may modestly increase cardiovascular risk; effect is small - once weekly red mead unlikely to contribute to cardiovascular risk also see QRISK score - low serum DHEA-S levels predict cardiovascular events due to coronary artery disease (MI, acute coronary syndrome ..) in elderly men [102] - no association of serum DHEA-S & cardiovascular events due cerebrovascular disease (TIA, ischemic stroke) [102] - variations in NPC1L1 that inhibit its function that lower plasma LDL cholesterol levels & a reduce the risk of coronary artery disease [103] - hospitalization for pneumonia in middle-aged & older adults (RR=4.1, risk greatest within 30 days) [111] - gout (RR=1.06 men, 1.25 women) [115] - shorter adult height due to - height-associated genetic variants (major factor) - higher LDL cholesterol & plasma triglycerides [117] - trauma (including unwanted sexual contact) in women [119] * greatest risk factors for myocardial infarction * 9 modifiable risk factors account for > 90% of acute MI, in descending order: 1) dyslipidemia 2) smoking (smoking cessation has greatest impact on reduction of mortality) [1] 3) psychosocial stress 4) diabetes mellitus (greater risk factor than dyslipidemia [1]) 5) hypertension 6) obesity $ 7) alcohol consumption 8) physical inactivity 9) diet low in fruits & vegetables ** hypertension is relatively more important for stroke # only marker that predicts cardiovascular mortality in the very old [28] also see cardiovascular risk calculator (numerous) [138] Postulated risk factors for CAD: - Chlamydia pneumonia infection - no role for antibiotic treatment in CAD [9] see CLARICOR trial - immune complexes (i.e. lupus erythematosus) - poor oral hygiene a) brushing teeth < twice a day) [41] b) association with periodontal disease, not causality [48] c) treatment of periodontitis improves endothelial function & reduces biomarkers of atherosclerotic disease [93] d) transient increase in risk (4 weeks) after invasive dental procedure [48] - low plasma antioxidants - mediastinal irradiation - dietary saturated fat [38]; not a risk factor 122] - small, dense LDL particles - increased Lp - increased VLDL remnants - increased IDL - xanthelasma - leukocytosis - thrombocytosis & increased platelet activity - increased fibrinogen - increased factor VIIa - hypercoagulability a) factor V Leiden mutation b) prothrombin mutation [76] - chronic inflammation [2] - WBC > 6700/mm3 in postmenopausal women (HR = 1.4-2.4) [8] - family history of premature cardiovascular disease [3,63] - increased serum N-terminal proBNP (HR=1.82, risk=24%)* [6] - increased serum CRP (HR=1.46, risk=7.8%)* - increased urinary albumin/creatinine (HR=1.88, risk=20%)* - shorter telomere length in peripheral blood leukocytes [98] - shorter telomere length in peripheral blood mononuclear cells [20] - glucocorticoid receptor haplotype 3 [23] - SNP profile may contribute to differences in lipid profiles & perhaps cardiac risk [24] - increased weight gain relative to height during an infant's first 3 months of life [32] - thigh circumference [35] - living within 328 feet of a freeway [39] - recurrent miscarriages or a stillbirth [49] - screen entertainment time (television &/or computer screen) - risk independent of physical activity [52] - diet soda [56] - Na+ & K+ consumption/secretion: - low Na+/K+ consumption may diminish risk [57] - delivery of small for gestational age infant [65] - circulating endothelial cells may be risk factor for myocardial infarction [90] * hazzard ratio (HR) & absolute risk increase for highest 20% of elderly population (cardiovascular event & mortality) NOT risk factors: 1) not NSAIDs - excluding rofecoxib (Vioxx), diclofenac [17,42] 2) not serum DHEA, serum testosterone [19] 3) not most putative genetic risk factors [21] 4) not fried foods (olive oil or sunflower oil) [60] 5) not serum uric acid; a confounder, not risk factor [79] 6) saturated fat [86,122] Epidemiology: - most Americans have suboptimal cardiovascular health parameters as measured by life's simple 7 (LS7) [165] - from 1988 to 2014, disparities in cardiovascular health between whites & non-whites diminished due to worsening cardiovascular health measures in whites [165] - 9.5% of Chinese (age 35-75 years) at high CVD risk (men:11.8%; women:8.0%) [173] Laboratory: - fasting lipid panel - USPSTF recommends screening all adults 40-75 years with lipid panel as part of calculating cardiovascular disease risk using the Pooled Cohort Equations [1] - lipid panel 4-12 weeks after initiation of statin therapy to assess - adherence to medication - response to statin therapy [1] - cholesterol efflux capacity may predict cardiovascular risk better than HDL cholesterol or HDL particle size [105] - high-sensitivity serum C-reactive protein [69] a) recommended in men >= 50 or women >= 60 to determine if they might benefit from statin therapy for primary prevention [51] b) might be reasonable in men >= 50 & women >= 60 if intermediate risk; not recommended for low or high risk patients [1] c) USPSTF: insufficient evidence to recommend for or against high-sensitivity serum CRP [73,159,169] - plasma fibrinogen [69] - in patients at intermediate risk, no benefit of a) genetic testing b) advanced lipid testing c) serum natriuretic peptide [51] - renal function tests a) diminished glomerular filtration rate & microalbuminuria/ albuminuria are risk factors for cardiovascular disease b) add little to traditional cardiovascular risk factors for stratifying cardiovascular risk but do improve risk stratification for renal outcomes [54] - serum NT-proBNP only laboratory test that improved prediction of coronary artery disease with Framingham risk score (HR > 2 for 10 year risk) HR=2.5 [66] - HgbA1c or glycated hemoglobin (with or without diabetes) not associated with improvement in assessment of CVD [95] * also see ARUP consult [178] Special laboratory: - ankle-brachial index (ABI) < 0.7 & declining serial ABI may predict adverse cardiovascular outcomes [27] - MKSAP17 suggests ABI of < 0.9 is risk factor - USPSTF: insufficient evidence to recommend [159,169] - screening for abdominal aortic aneurysm (AAA) - in patients at intermediate risk, no benefit of - stress echocardiography [51] - carotid ultrasound - measurement of carotid-intima-media thickness (CMIT) reasonable if site (of testing) proficient [51] - insufficient evidence to recommend for or against screening in higher-risk patients (see screening for coronary artery disease) - routine screening in asymptomatic patients with diabetes mellitus does not reduce mortality (see diabetes mellitus type 2) - measure waist circumference in overweight patients - indicator of risk for metabolic syndrome [1] - cost-effective cardiovascular risk stratification tool [1] - screening with abdominal ultrasound for AAA, ABI for PAD, blood pressure for hypertension, & serum cholesterol for hypercholesterolemia may diminish all-cause mortality in men (10.2 vs 10.8%) [156] - screening with electrocardiogram not indicated (USPSTF) [157] - the U.S. Preventive Services Task Force recommends calculating the cardiovascular disease risk in adults aged 40-75 years using the Pooled Cohort Equations. - cardiovascular risk calculator - 10 year risk of 7.5%-20% considered intermediate risk [172] Radiology: - in patients at intermediate risk, no benefit of a) coronary computed tomography angiography b) magnetic resonance imaging for the detection of vulnerable plaques [51] - coronary artery calcium score > 300 (75th percentile) - USPSTF concludes insufficient evidence to recommend for or against [159,169] - carotid artery calcium - intermediate risk patients [51] - patients >= 40 with diabetes mellitus - serial testing not advised - only imaging test that improved prediction of coronary artery disease with Framingham risk score (HR > 2 for 10 year risk) HR=6.2 [66] Management: 1) diet & lifestyle modifications are the cornerstone of management [34,172] a) treat unhealthy behaviors such as smoking, poor diet, & lack of exercise as aggressively as hypercholesterolemia, hypertension, & cardiovascular risk factors [85] b) walking & running offer comparable benefits with similar total energy expenditures [75] c) bicycling to work associated with reduced all-cause mortality vs driving or public transportation (RR=0.59) [149] d) benefits of physical activity extend to people at high genetic risk for cardiovascular events [166] e) Mediterranean diet may be better than low-fat diet [18] f) 4 of 5 MIs in men are preventable through healthy diet & lifetyle [107] - this translates to a number needed to treat of 20 for 10 years to prevent 1 MI [107] g) precedence for effectiveness of community prevention programs [110] h) peer-led group sessions plus educational training may be of benefit [128] i) improved intakes of polyunsaturated fats & nuts & seeds & lower intake of sugar-sweetened beverages reduced diet-related cardiovascular mortality in the U.S. by 25% from 2002-2012 [147] j) health plant-based diet associated with reduced cardiovascular risk [154] 2) obtain Framingham risk score (or equivalent) on all asymptomatic adults [51] - other risk scores may be appropriate [72] 3) aspirin 81-162 mg QD or clopidogrel 75 mg QD* - secondary risk reduction - USPSTF reccommends low-dose aspirin for primary prevention of both cardiovascular disease & colorectal cancer in adults 50-59 years of age with a 10-year cardiovascular risk of >= 10% [125, 132] - adults 60-69 years of age should discuss risks & benefits with their clinicians [125, 132] - routine use of aspirin no longer recommended for primary prevention [187] - AHA/ACC recommends low-dose aspirin for primary prevention in patients at high cardiovascular risk but low risk of bleeding [187] - anticoagulation confers high risk of bleeding [187] - risk using pooled cohort equations does not outweigh risk of anticoagulation - 81 mg aspirin with anticoagulation if myocardial infarction in past year [187] - in men age 45-79 years, low-dose aspirin is recommended for primary prevention of MI if benefit outweighs risk of GI bleed [1] - cardiovascular risk > 4% 45-59; > 9% 60-69; > 12% 70-79 - metabolic syndrome & 10 year cardiovascular risk > 10% [1] - in women age 55-79 years, aspirin is recommended for primary prevention of stroke if benefit outweighs risk of GI bleed [1] - cardiovascular risk > 3% 55-59; > 8% 60-69; > 11% 70-79 - insufficient evidence to recommend aspirin for patients > 79 years of age or in men < 45 or women < 55 years of age [1] - benefit of continuing aspirin after upper GI bleed or lower GI bleed outweigh the harms in patients at high cardiovascular risk [140] - aspirin is not routine for diabetics at low risk [1] - patients with 10-year cardiovascular risk >= 6% [109] - low-dose aspirin no benefit in primary prevention for Japanese men > 60 years of age [104] - low-dose aspirin does not prevent primary cardiovascular events in black patients [177] 4) statins# (see statin, & dyslipidemia) - high-intensity statin (atorvastatin 40 mg QD or rosuvastatin 20 mg QD) for patients with: - known cardiovascular disease - dose to achieve > 50% reduction in LDL cholesterol - add ezetimibe as needed & then a PCSK9 inhibitor for high-risk patients with LDL cholesterol > 70 mg/dL [172] - mortality risks decrease as statin doses increase [143] - 10 year cardiovascular risk >= 20% [1] - LDL cholesterol > 190 mg/dL, add ezetimibe as needed [172] - treat-to-target LDL cholesterol 50-70 mg/dL non-inferior to high-intensity statins for patients with coronary artery disease [185] - moderate dose statin for intermediate cardiovascular risk - LDL-cholesterol > 70 mg/dL AND - diabetes mellitus OR - 10 year cardiovascular risk >= 7.5%-20% (AHA/ACC) [1,151,172]; >= 10% (USPSTF) [150] - if asymptomatic & coronary artery calcium score = 0, no statin needed [1] - high-dose statin indicated but - age > 75 years [139] - renal isufficiency - coadministration of drug that inhibits statin metabolism [1] - ezetimibe 10 mg recommended as 1st add on to statin therapy [131] - moderate intensity statin + ezetimibe as effective as high-intensity statin & better tolerated [183] - PCSK9 inhibitor in conjunction with statin may benefit patients with LDL cholesterol not at target (see PCSK9 inhibitor) - adding PCSK9 inhibitor or ezetimibe to a statin lowers CV risk in patients with 5-year CV risk > 15%, but not in patients with lower risk [182] - see laboratory for monitoring response to therapy [1] - VA guidelines recommend no target LDL cholesterol] (see dyslipidemia) 5) colchicine 0.5 mg QD FDA approved for cardiovascular risk reduction in high-risk patients 6) beta-blockers do not reduce risk of cardiovascular events - except after myocardial infarction [70] 7) ACE inhibitor for secondary prevention [1] 8) treatment induced lowering of LDL-cholesterol lowers cardiovascular risk, whereas treatment induced increase of HDL-cholesterol does not [30] 9) management of chronic hypertension - JNC8 recommends blood pressure < 140/90 mm Hg for most patients & < 140/90 mm Hg for older adults > 60 years (see JNC8) - for subgroup & differing management strategies, see chronic hypertension - intensity of blood pressure control based on cardiovascular risk may improve cardiovascular outcomes [100] - more intensive systolic blood pressure control, target = < 120 mm Hg for patients at high risk for heart disease or with kidney disease may reduce cardiovascular events & mortality [124] - a systematic review of blood pressure guidelines in the elderly [180] - conclusions differ from ref [124] 10) guideline-recommended cardiovascular drugs (calcium-channel blockers, statins, beta-blockers, ACE inhibitors & ARBs) appear to confer a survival benefit in older adults with multiple comorbidities (see survival) 11) influenza vaccine in patients with established cardiovascular disease to reduce risk of cardiovascular events [1] 12) behavioral modification - behavioral counseling of high-risk patients of small benefit [101] - a simple text messaging program to promoting healthy lifestyle can improve cardiovascular risk factors [126] - telehealth approach using lay persons trained in motivational interviewing following software-generated scripts that addressed diet, exercise, weight management, tobacco & alcohol use, medication adherence, & home blood pressure monitoring associated with small clinical benefits for a minority of people with high cardiovascular risk [137] - USPSTF suggests behavioral counseling towards promoting a healthful diet & exercise may be warranted in adults without risk factors [144] 13) moderate consumption of alcohol reduces risk of coronary artery disease in men 14) dietary factors (also see prevention of cardiovascular disease) a) soluble (viscous) fiber lowers LDL cholesterol & estimated 10-year cardiovascular risk [139] b) omega-3 fatty acids (DHA, EPA) - omega-3 fatty acids & statins favorably affect risk profiles & diminish overall mortality [7] - no cardiovascular risk benefit of omega-3 fatty acids [161] c) benefit of dairy uncertain d) regular tea intake (>= 1 cup/day) & higher caffeine intake associated with slower progression of coronary artery calcium & a reduced risk of cardiovascular events [146] - coffee intake without effect [146] e) Mediterranean diet & low-fat diet reduce all-cause & cardiovascular mortality in persons with cardiovascular risk factors [186] 15) dog ownership reduces cardiovascular risk, possibly by the exercise associated with regularly walking the dog [77] 16) in Finland, frequent sauna use reduces risk of sudden cardiac death (RR=0.37) [114] 17) multivitamins & antioxidants of no benefit [71,118] - vitamin D of no benefit (100,000 IU monthly) [148] * but not in combination see MATCH study & CHARISMA trial # may not be of benefit in the elderly (> 80) [14] Notes: Other Factors - Fitness & Overweight: improvements in one measure somewhat, but not completely, offset deteriorations in the other - some, but not all, common outward signs of aging are associated with increased cardiovascular risk - male balding pattern, earlobe creases, xanthelasma are associated with increased cardiovascular risk [92] - gray hair, arcus corneae, wrinkles are not country-specific cardiovascular disease mortality risk model [116] pharmacist-administered medication therapy management program in high risk patients (dyslipidemia, diabetes mellitus, hypertension, smokers) lowers cardiovascular risk scores [133] numerous cardiovascular risk calculators [138] Healthy Heart Score is relatively accurate in predicting future cardiovascular events in young adults [155] USPSTF concludes current evidence is insufficient to assess benefits vs harms of adding the ankle-brachial index, high-sensitivity CRP in serum, or coronary arter calcium score to traditional risk assessment for cardiovascular disease in asymptomatic adults

Related

cardiac risk assessment cardiac risk index (CRI) cardiovascular disease (CVD) cardiovascular risk calculator; cardiovascular risk score cerebrovascular disease/disorder coronary artery disease; coronary atherosclerosis (CAD) Framingham Risk Score/Calculator HEART Score for major cardiac events primary prevention of cardiovascular disease risk factors for & prevention of ischemic stroke secondary prevention in patients with cardiovascular disease

Specific

cardiometabolic disorder risk factors for coronary artery disease in patients with diabetes mellitus type-2

General

health risk factor(s)

References

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