Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk

OBJECTIVES: This prospective population study was conducted to assess the role of elevated lipoprotein(a) [Lp(a)] as a coronary risk factor. BACKGROUND: The role of elevated Lp(a) as a risk factor for coronary heart disease is controversial. In addition, little attention has been paid to the interaction of Lp(a) with other risk factors. METHODS: A total of 788 male participants of the Prospective Cardiovascular Münster (PROCAM) study aged 35 to 65 years were followed for 10 years. Both Lp(a) and traditional cardiovascular risk factors (e.g., age, low density lipoprotein [LDL] cholesterol, high density lipoprotein [HDL] cholesterol, triglycerides, systolic blood pressure, cigarette smoking, diabetes mellitus, angina pectoris, and family history of myocardial infarction) were evaluated in 44 men who suffered from myocardial infarction, and in 744 men who survived without major coronary events or stroke. A multiple logistic function algorithm was used to estimate global cardiovascular risk by the combined effects of traditional risk factors. RESULTS: Overall, the risk of a coronary event in men with an Lp(a) > or =0.2 g/liter was 2.7 times that of men with lower levels (95% confidence interval [CI]: 1.4 to 5.2). This increase in risk was most prominent in men with LDL cholesterol level > or =4.1 mmol/liter (relative risk [RR]: 2.6; 95% CI: 1.2 to 5.7), with HDL cholesterol < or =0.9 mmol/liter (RR 8.3; 95% CI: 2.0 to 35.5), with hypertension (RR 3.2; 95% CI: 1.4 to 7.2), or within the two highest global risk quintiles (relative risk: 2.7; 95% CI: 1.3 to 5.7). CONCLUSIONS: Lp(a) increases the coronary risk, especially in men with high LDL cholesterol, low HDL cholesterol, hypertension and/or high global cardiovascular risk.     

Apolipoprotein B and Non-HDL Cholesterol Better Reflect Residual Risk Than LDL Cholesterol in Statin-Treated Patients

BackgroundIn cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non–high-density lipoprotein (non-HDL) cholesterol are secondary targets.ObjectivesThis study sought to determine if elevated apoB and/or non-HDL cholesterol are superior to elevated LDL cholesterol in identifying statin-treated patients at residual risk of all-cause mortality and myocardial infarction.MethodsIn total, 13,015 statin-treated patients from the Copenhagen General Population Study were included with 8 years median follow-up. Cox regressions among apoB, non-HDL cholesterol, and LDL cholesterol, respectively, and all-cause mortality or myocardial infarction were examined on continuous scales by restricted cubic splines and by categories of concordant and discordant values defined by medians.ResultsHigh apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction, whereas no such associations were found for high LDL cholesterol. Compared with concordant values below medians, discordant apoB above the median with LDL cholesterol below yielded hazard ratios of 1.21 (95% confidence interval [CI]: 1.07 to 1.36) for all-cause mortality and 1.49 (95% CI: 1.15 to 1.92) for myocardial infarction. Corresponding values for high non-HDL cholesterol with low LDL cholesterol were 1.18 (95% CI: 1.02 to 1.36) and 1.78 (95% CI: 1.35 to 2.34). In contrast, discordant high LDL cholesterol with low apoB or non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Also, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 (95% CI: 1.03 to 1.41) for all-cause mortality and of 0.93 (95% CI: 0.62 to 1.40) for myocardial infarction. Furthermore, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below presented hazard ratios of 1.23 (95% CI: 1.07 to 1.43) for all-cause mortality and 1.82 (95% CI: 1.37 to 2.42) for myocardial infarction.ConclusionsIn statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol.     

Cholesterol 2001. Rationale for lipid-lowering in older patients with or without CAD

Statin treatment of men and women age > or = 50 with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, and intermittent claudication. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg/dL in older patients with CAD, prior stroke, peripheral arterial disease, or extracranial carotid arterial disease and serum LDL cholesterol > 125 mg/dL despite diet therapy. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia but without cardiovascular disease. Consider using statins in patients age 50 to 80 without cardiovascular disease, serum LDL cholesterol > 130 mg/dL, and serum high-density lipoprotein (HDL) cholesterol < 50 mg/dL.     

Influence of high-density lipoprotein cholesterol and rheological factors on the sex difference in cardiovascular disease

BACKGROUND: It is well established that the incidence of cardiovascular disease among men is higher than that among women. OBJECTIVE: To determine whether differences between men and women in terms of a range of conventional and rheological risk factors could explain this sex difference. DESIGN: This was a population-based cohort study (the Edinburgh Artery Study). METHODS: Men and women aged 55-74 years (n = 1592) were selected at random from the general population of Edinburgh and followed up for 5 years. Baseline cardiovascular risk factors were measured and related to incidence of disease among men and women. RESULTS: Men had higher levels of cigarette smoking, haematocrit and blood viscosity and lower levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and plasma fibrinogen than did women. The incidences of cardiovascular events among men and women were 48.3 and 26.1 per 1000 person-years, respectively. Adjustment for level of HDL cholesterol reduced the male:female ratio for sex-specific incidence rates of cardiovascular events from 1.80 [95% confidence interval (CI) 1.43-2.27] to 1.34 (95% CI 1.04-1.73). This reduction was partially reversed after further adjustment for the other cardiovascular risk factors. The impact of blood viscosity, plasma viscosity and plasma level of fibrinogen on the risk of cardiovascular disease was higher for men than it was for women (multivariate relative risk for blood viscosity were 1.24, 95% CI 1.08-1.43, for men and 0.81, 95% CI 0.61-1.06, for women). CONCLUSIONS: Levels of HDL cholesterol levels in women being higher than those in men may explain some, but not all, of the sex difference in incidence of cardiovascular disease. Greater susceptibility of men to rheological factors might also be important.     

Improved identification of patients with coronary artery disease by the use of new lipid and lipoprotein biomarkers

Increasing attention is being directed toward new lipid and lipoprotein biomarkers as risk factors for coronary artery disease, although limited information is available on the diagnostic accuracy of these new biomarkers for the identification of patients with coronary artery disease. In the present study, levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized LDL/HDL cholesterol were determined in 431 apparently healthy men and women without clinical evidence of coronary artery disease who were matched for age and gender with 490 men and women with coronary artery disease who participated in the Second Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC-II) trial. Diagnostic accuracy was determined by receiver-operating characteristic curve analysis by measuring the area under the curve. The diagnostic accuracies of each lipid or lipoprotein biomarker (in descending order of area under the curve) were 0.867 for oxidized LDL/HDL cholesterol (95% confidence interval [CI] 0.844 to 0.890), 0.826 for oxidized LDL (95% CI 0.800 to 0.852), 0.775 for 1/HDL cholesterol (95% CI 0.745 to 0.805), 0.764 for total/HDL cholesterol (95% CI 0.733 to 0.795), 0.631 for triglycerides (95% CI 0.594 to 0.667), 0.597 for Lp-PLA2 (95% CI 0.558 to 0.615), 0.577 for LDL cholesterol (95% CI 0.539 to 0.615), and 0.520 for total cholesterol (95% CI 0.482 to 0.537). In conclusion, these findings indicate that the ratio of oxidized LDL to HDL cholesterol was a more potent biomarker for discriminating between subjects with and without coronary artery disease than traditionally measured lipids and lipoproteins and Lp-PLA2.     

Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women.

BACKGROUND: Elevated fasting total homocysteine (tHcy) levels were recently shown to confer an independent risk for all-cause and cardiovascular disease (CVD) mortality among selected Norwegian patients with confirmed coronary heart disease. We examined whether elevated fasting plasma tHcy levels were predictive of all-cause and CVD mortality in a large, population-based sample of elderly US women and men. METHODS: Nonfasting plasma tHcy levels were determined in 1933 elderly participants (mean age, 70 +/- 7 years; 58.9% women) from the original Framingham Study cohort, examined between 1979 and 1982, with follow-up through 1992. Unadjusted and adjusted (ie, for age, sex, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol, and creatinine) relative risk estimates (with 95% confidence intervals [CIs]) for total and CVD mortality were generated by proportional hazards modeling, with tHcy levels (quartiles) as the independent variable. RESULTS: There were 653 total deaths and 244 CVD deaths during a median follow-up of 10.0 years. Proportional hazards modeling revealed that tHcy levels of 14.26 micromol/L or greater (the upper quartile), vs less than 14.26 micromol/L (the lower three quartiles), were associated with relative risk estimates of 2.18 (95% CI, 1.86-2.56) and 2.17 (95% CI, 1.68-2.82) for all-cause and CVD mortality, respectively. The relative risk estimates after adjustment for age, sex, systolic blood pressure, diabetes, smoking, and total and high-density lipoprotein cholesterol levels attenuated these associations, but they remained significant: 1.54 (95% CI, 1.31-1.82) for all-cause mortality; 1.52 (95% CI, 1.16-1.98) for CVD mortality. CONCLUSION: Elevated nonfasting plasma tHcy levels are independently associated with increased rates of all-cause and CVD mortality in the elderly.     

Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality

BackgroundReduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.ObjectivesThis study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.MethodsA total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.ResultsAn increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.ConclusionsGenetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population.     

HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men

BACKGROUND. We investigated the association of cholesterol concentrations in serum high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 with the risk of acute myocardial infarction in 1,799 randomly selected men 42, 48, 54, or 60 years old. METHODS AND RESULTS. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study were done during 1984-1987. In Cox multivariate survival models adjusted for age and examination year, serum HDL cholesterol of less than 1.09 mmol/l (42 mg/dl) was associated with a 3.3-fold risk of acute myocardial infarction (95% confidence intervals [CI], 1.7-6.4), serum HDL2, cholesterol of less than 0.65 mmol/l (25 mg/dl) was associated with a 4.0-fold risk of acute myocardial infarction (95% CI, 1.9-8.3), and serum HDL3 cholesterol of less than 0.40 mmol/l (15 mg/dl) was associated with a 2.0-fold (95% CI, 1.1-4.0) risk of acute myocardial infarction. Adjustments for obesity, ischemic heart disease, other cardiovascular disease, maximal oxygen uptake, systolic blood pressure, antihypertensive medication, serum low density lipoprotein cholesterol, and triglyceride concentrations reduced the excess risks associated with serum HDL, HDL2, and HDL3 cholesterol in the lowest quartiles by 52%, 48%, and 41%, respectively. Additional adjustments for alcohol consumption, cigarettes smoked daily, smoking years, and leisure time energy expenditure reduced these excess risks associated with low HDL, HDL2, and HDL3 cholesterol levels by another 26%, 24% and 21%, respectively. CONCLUSIONS. Our data confirm that both total HDL and HDL2 levels have inverse associations with the risk of acute myocardial infarction and may thus be protective factors in ischemic heart disease, whereas the role of HDL3 remains equivocal.     

Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: a prospective study

BACKGROUND: Patients with newly diagnosed rheumatoid arthritis have adverse serum lipid profiles. We sought to determine the effects of treating rheumatoid arthritis with antirheumatic drugs on these abnormal lipid levels. SUBJECTS AND METHODS: We studied 42 patients with newly diagnosed rheumatoid arthritis who had not been treated with corticosteroids or disease-modifying antirheumatic drugs. We measured serum lipid profiles at baseline and 1 year later, and determined whether there were differences in the changes in lipid levels between patients who met the American College of Rheumatology criteria for a 20% improvement in rheumatoid arthritis and those who did not. RESULTS: Of the 42 patients, 27 (64%) met the criteria for a 20% improvement in rheumatoid arthritis during the 12-month study. In these patients, mean high-density lipoprotein (HDL) cholesterol levels increased by 21% (P <0.001), apolipoprotein A-I levels increased by 23% (P <0.001), and the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol level decreased by 13% (P = 0.10). There were significant between-group differences (responders-nonresponders) in the mean 12-month changes in HDL cholesterol levels (8.0 mg/dL; 95% confidence interval [CI]: 3 to 13 mg/dL; P = 0.002), apolipoprotein A-I levels (21 mg/dL; 95% CI: 8 to 33 mg/dL; P = 0.003), and the LDL cholesterol to HDL cholesterol ratio (-0.6; 95% CI: -0.1 to -1.0; P = 0.03), but not in LDL cholesterol, apolipoprotein B-100, or lipoprotein(a) levels. CONCLUSION: Active rheumatoid arthritis is associated with an adverse lipid profile that improves substantially following effective treatment of rheumatoid arthritis. This improvement may reduce the risk of cardiovascular disease.     

Dietary glycemic index, dietary glycemic load, blood lipids, and C-reactive protein

Carbohydrate quantity and quality may influence the risk of cardiovascular disease through blood lipid concentrations and inflammation. We measured dietary glycemic index (GI) and dietary glycemic load (GL) among 18137 healthy women > or = 45 years old without diagnosed diabetes using a food-frequency questionnaire. We assayed fasting total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol; LDL/HDL cholesterol ratio; triacylglycerols (TG); and C-reactive protein (CRP). We evaluated associations with dietary GI and GL using a cross-sectional design, adjusting for age, body mass index, lifestyle factors, and other dietary factors. Dietary GI was significantly associated with HDL and LDL cholesterol, LDL/HDL cholesterol ratio, TG, and CRP (comparing top to bottom quintile difference in HDL cholesterol = -2.6 mg/dL, LDL cholesterol = 2.2 mg/dL, LDL/HDL cholesterol ratio = 0.16, TG = 12 mg/dL, and CRP = 0.21 mg/L). Dietary GL was associated with HDL cholesterol, LDL/HDL cholesterol ratio, and TG (comparing top to bottom quintile HDL cholesterol = -4.9 mg/dL, LDL/HDL cholesterol ratio = 0.24, and TG = 13 mg/dL). Differences in blood lipids and CRP between extreme quintiles of dietary GI and GL were small, but may translate into a clinically meaningful difference in cardiovascular risk.     

Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study

BACKGROUND: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol. METHODS: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years' follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding variables. RESULTS: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline. CONCLUSIONS: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia.     

Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study

The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.     

Low-risk profile for cardiovascular disease and mortality in Japanese.

BACKGROUND: Some studies focusing on low-risk profiles for cardiovascular disease have been reported in Western countries. Yet, few reports have examined, with substantial longevity, the low-risk profile for cardiovascular disease in the Japanese population. This study examines whether having a favorable risk factor profile yields lower all-cause mortality and whether the proportion of those with a low-risk profile is larger in the Japanese population. METHODS AND RESULTS: A total of 8,339 men and women aged 30-69 years without a history of cardiovascular diseases for 19 years, who had participated in the 1980 National Survey on Circulatory Disorders after being randomly selected from throughout Japan, were followed. Low risk was defined as having all of the following baseline characteristics: blood pressure (BP) <120/80 mmHg; no antihypertensive medication; serum cholesterol 160-240 mg/dl (4.14-6.22 mmol/L); no history of diabetes; and non-smoker. The long-term mortality of the low-risk group was compared with that of others using the Cox proportional hazard model. The prevalence of low risk was 9.4% of all participants. The multivariate-adjusted hazard ratios for low-risk individuals compared with others were as follows: 0.33 (95% confidence intervals (CI), 0.15-0.74) for cardiovascular disease and 0.63 (95% CI, 0.46-0.88) for all-cause mortality. The most attributable risk factor for all-cause mortality was high BP (>or=120/80 mmHg). CONCLUSION: Japanese individuals with favorable cardiovascular disease risk profiles had lower mortality from cardiovascular disease and all-causes than those without.     

Long-term predictors of survival for the Seven Countries Study cohort from Crete: from 1960 to 2000

BACKGROUND: In 1960, all male inhabitants of a series of villages in rural Crete, born between 1900 and 1919, were invited to participate in the Seven Countries Study. Analysis of 25-year mortality data from the 16 cohorts of participants indicated that the cohort from Crete had the lowest age-standardised all-cause and coronary heart disease death rates. METHODS: At baseline, 686 Cretan men (98% of those invited) participated in health examinations. Mortality data were collected over 40 years. Time-fixed and updated covariate survival analysis techniques were applied to assess eight cardiovascular disease risk factors as long-term predictors of all-cause and cardiovascular disease mortality. RESULTS: The median survival time was 32 years. All-cause and cardiovascular mortality rates were 26 and 11 per 1000 person-years, respectively. Age (relative risk 1.11, 95% CI 1.09-1.13), diastolic blood pressure (relative risk 1.02, 95% CI 1.01-1.03), and smoking (relative risk 1.37, 95% CI 1.14-1.64) were positively associated and forced expiratory volume (relative risk 0.50, 95% CI 0.36-0.68) was negatively associated with all-cause mortality. Age (relative risk 1.13, 95% CI 1.09-1.16), diastolic blood pressure (relative risk 1.01, 95% CI 1.001-1.03), and forced expiratory volume (relative risk 0.53, 95% CI 0.32-0.89) were independent predictors of cardiovascular mortality. Serum cholesterol concentration and body mass index were not independently associated with death risk. CONCLUSIONS: The Cretan cohort displays favourable 40-year survival. Even so, long-term predictors of the hazard of both all-cause and cardiovascular disease mortality are present.     

Hypercholesterolemia. The evidence supports use of statins

Using statins to treat older men and women with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, Intermittent claudication, and congestive heart failure. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg in older patients with CAD, prior stroke, peripheral arterial disease, extracranial carotid arterial disease, abdominal aortic aneurysm, diabetes meilitus, and the metabolic syndrome. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia without cardiovascular disease. Consider using statins in older persons without cardiovascular disease but with a serum LDL cholesterol > or = 130 mg/dL, or a serum high-density lipoprotein cholesterol < 50 mg/dL. Data from the Heart Protection Study favor treating patients at high risk for vascular events with statins regardless of age or initial serum lipids.     

Does Inflammation or Undernutrition Explain the Low Cholesterol–Mortality Association in High‐Functioning Older Persons? MacArthur Studies of Successful Aging

OBJECTIVES: To explore the effect of inflammation and undernutrition on the association between hypocholesterolemia and higher overall mortality in high-functioning older persons. DESIGN: Prospective cohort study. SETTING: Three U.S. communities. PARTICIPANTS: A cohort of 870 participants from the MacArthur Studies of Successful Aging. MEASUREMENTS: Baseline information was obtained for serum levels of cholesterol, C-reactive protein, interleukin-6, and albumin; body mass index; prevalent medical conditions; health behaviors; and medications. Crude and multivariate logistic regression analyses were used to examine the association between serum total cholesterol levels and 7-year all-cause mortality, while adjusting for potential confounders. RESULTS: In univariate analysis, the risk ratio of low serum total cholesterol level (<169 mg/dL) for 7-year total mortality was 1.90 (95% confidence interval (CI) = 1.18-3.07). The multiple adjusted risk ratios were 1.82 (95% CI = 1.10-3.00) after controlling for markers of inflammation and nutrition and 1.39 (95% CI = 0.80-2.40) after adjustment for additional cardiovascular risk factors. Sex was an important confounding variable that contributed to the observed inverse association between low serum cholesterol and overall mortality in univariate analysis. CONCLUSIONS: Hypocholesterolemia is not an independent risk factor for increased overall mortality in high-functioning community-dwelling older men and women. The association between low total cholesterol and high mortality observed in crude analysis is mainly confounded by common cardiovascular risk factors, rather than underlying inflammation or undernutrition.     

Serum lipids and lipoproteins after myocardial infarction: associations with cardiovascular mortality and experience in the Aspirin Myocardial Infarction Study

Serum cholesterol and triglyceride levels were measured at baseline in 4021 men and 503 women (myocardial infarction survivors) participating in the Aspirin Myocardial Infarction Study (AMIS). A cohort of participants (1824 men and 226 women) had, in addition, a determination of high-density lipoprotein (HDL) cholesterol and an estimate of low-density lipoprotein (LDL) cholesterol. In comparison with values obtained for normal Americans by the Lipid Research Clinics Prevalence Study Group, AMIS participants had higher serum cholesterol, higher serum triglyceride, higher LDL cholesterol, and lower HDL cholesterol levels. These values were the most disparate in the women and younger men. The serum total cholesterol, the ratio of LDL to HDL cholesterol, and the serum triglyceride level were significantly related (p less than 0.05) to the 3-year cardiovascular mortality rate for men less than 55 years of age (univariate relationships). For men older than 55 years, these relationships were not statistically significant. After adjustment for multiple risk factors, serum cholesterol and the ratio of LDL to HDL cholesterol remained significant risk factors for cardiovascular death and the combined incidence of cardiovascular death or nonfatal myocardial infarction in men less than age 55 years.     

Cholesterol and other lipids predict coronary heart disease and ischaemic stroke in the elderly, but only in those below 70 years.

The prediction of coronary heart disease (CHD) and stroke by total and low density lipoprotein (LDL) cholesterol in older persons remains problematical. This study tests the hypothesis that cholesterol and other risk factors may be differentially predictive of CHD and ischaemic stroke in older persons when they are segregated into different age groups. CHD and ischaemic stroke outcomes were recorded during 129 months follow-up in a cohort of 2805 men and women of 60 years and older. There were 899 CHD events (32/100) and 326 stroke events (12/100). Using Cox proportional hazards, outcomes were modelled for the total cohort and for age groups 60-69, 70-79, and 80+ years. Total cholesterol, LDL cholesterol, serum apo-B, total cholesterol/high density lipoprotein (HDL) cholesterol and apo-B/apo-A1 were significant predictors of CHD in the total cohort, but significant only in the sub-group of 60-69 years. The respective hazard ratios (CI 95%) were 1.21 (1.09-1.35), 1.21 (1.09-1.35), 1.25 (1.13-1.39), 1.25 (1.14-1.37) and 1.21 (1.10-1.38). Similar findings were applicable with respect to ischaemic stroke in the age group of 60-69 years. Total cholesterol predicted CHD in men above a threshold value of 7.06 mmol/l and in women above 7.8 mmol/l, but with stroke the prediction was incremental. Other risk factors such as HDL cholesterol, triglycerides, lipoprotein(a), diabetes, hypertension and smoking predicted CHD, although only HDL and hypertension similarly predicted ischaemic stroke. The findings support a case for cholesterol testing in older subjects up to 70 years, in whom there is ancillary evidence of CHD and stroke prevention through treatment designed to reduce LDL cholesterol.     

MEDPED and the Spanish Familial Hypercholesterolemia Foundation

We analysed clinical and genetic data of 819 non-related familial hypercholesterolemia patients. No differences on baseline low density lipoprotein (LDL) cholesterol levels between females and males were observed. High density lipoprotein (HDL) cholesterol values were higher in females than in males (57+/-15 vs. 47.7+/-13, respectively, P<0.01). Premature cardiovascular disease was present in 21.7% of cases (30.8% in males and 14.3% in females, P<0.001). A significant and positive correlation was observed between cardiovascular disease and age, gender, tobacco, total and LDL cholesterol levels at diagnosis, and negatively with HDL cholesterol levels. Analysis of LDL-receptor gene have been performed in 350 cases and 86 different mutations have been found.     

HDL cholesterol efflux capacity and incident cardiovascular events

Background It is unclear whether high-density lipoprotein(HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort.Methods We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probabilitybased population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years.Results In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis(hazard ratio, 1.08;95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors,HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile(hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes.Conclusions Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport,was inversely associated with the incidence of cardiovascular events in a population-based cohort.(From: N Engl J Med 2014; 371:2383-2393 December 18, 2014DOI: 10.1056 / NEJMoa1409065)