Dr. Ron’s Research Review – August 14, 2013

© 2013

This week’s research review focuses on high cholesterol.

A recent article found that some associations between total cholesterol and mortality risk were not linear but seemed to follow a 'U-shaped' curve. If valid, the clinical and public health recommendations regarding the 'dangers' of cholesterol should be revised. Moderately elevated cholesterol (by current standards) in women may prove to be not only harmless but even beneficial. (Petursson, Sigurdsson et al. 2012)

A 12-year follow-up cohort study with 800 people (60-85 years old) examined lipids and all-cause mortality among older adults. The data did not show a higher risk with high levels of total cholesterol (TC), LDL-c, and TG. However, they showed higher mortality among older adults with low TC (<170). (Cabrera, de Andrade et al. 2012)

A ten-year follow-up of ischemic strokes in the Copenhagen Stroke Study found that higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality. Because of selection, therefore, major strokes are more often seen in patients with lower cholesterol levels.  (Olsen, Christensen et al. 2007)

LDL Cholesterol

One study found that lower admission LDL cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke. (Bang, Saver et al. 2007)

Dr. Ron


Articles

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis

         (Bang, Saver et al. 2007) Download

BACKGROUND: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. METHODS: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. RESULTS: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. CONCLUSIONS: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

Lipids and all-cause mortality among older adults: a 12-year follow-up study

(Cabrera, de Andrade et al. 2012) Download

This is a 12-year follow-up cohort study with 800 people (60-85 years old). The association between lipid disorders and mortality was analysed by Cox proportional hazard adjusted model. All-cause mortality was considered the dependent variable, and lipid disorders as independent variables: total cholesterol (TC) >200 and <170 mg/dl, HDL-c <35 and 40, LDL-c >100 and 130, and triglycerides (TG) >50. An initial analysis of all subjects was performed and a second was carried out after having excluded individuals with a body mass index (BMI) <20 kg/m(2) or mortality in </= 2 years. The mortality showed a positive association with low TC and a negative association with high TC and high LDL-c. After the exclusion of underweight and premature mortality, there was a positive association only with TC <170 mg/dl (HR = 1.36, CI95%: 1.02-1.82). The data did not show a higher risk with high levels of TC, LDL-c, and TG. However, they showed higher mortality among older adults with low TC.

Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the Copenhagen Stroke Study

         (Olsen, Christensen et al. 2007)Download

BACKGROUND AND PURPOSE: Evidence of a causal relation between serum cholesterol and stroke is inconsistent. We investigated the relation between total serum cholesterol and both stroke severity and poststroke mortality to test the hypothesis that hypercholesterolemia is primarily associated with minor stroke. METHODS: In the study, 652 unselected patients with ischemic stroke arrived at the hospital within 24 hours of stroke onset. A measure of total serum cholesterol was obtained in 513 (79%) within the 24-hour time window. Stroke severity was measured with the Scandinavian Stroke Scale (0=worst, 58=best); a full cardiovascular risk profile was established for all. Death within 10 years after stroke onset was obtained from the Danish Registry of Persons. RESULTS: Mean+/-SD age of the 513 patients was 75+/-10 years, 54% were women, and the mean+/-SD Scandinavian Stroke Scale score was 39+/-17. Serum cholesterol was inversely and almost linearly related to stroke severity: an increase of 1 mmol/L in total serum cholesterol resulted in an increase in the Scandinavian Stroke Scale score of 1.32 (95% CI, 0.28 to 2.36, P=0.013), meaning that higher cholesterol levels are associated with less severe strokes. A survival analysis revealed an inverse linear relation between serum cholesterol and mortality, meaning that an increase of 1 mmol/L in cholesterol results in a hazard ratio of 0.89 (95% CI, 0.82 to 0.97, P=0.01). CONCLUSIONS: The results of our study support the hypothesis that a higher cholesterol level favors development of minor strokes. Because of selection, therefore, major strokes are more often seen in patients with lower cholesterol levels. Poststroke mortality, therefore, is inversely related to cholesterol.

Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study

         (Petursson, Sigurdsson et al. 2012) Download

RATIONALE, AIMS AND OBJECTIVES: Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline. METHODS: We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20-74, who participated in the Nord-Trondelag Health Study (HUNT 2, 1995-1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total). RESULTS: Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89-0.99 per 1.0 mmol L(-1) increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88-1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92-1.24) was not linear but seemed to follow a 'U-shaped' curve, with the highest mortality <5.0 and >/=7.0 mmol L(-1) . Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98-1.15) and in total (HR: 0.98; 95% CI: 0.93-1.03) followed a 'U-shaped' pattern. CONCLUSION: Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the 'dangers' of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.


References

Bang, O. Y., J. L. Saver, et al. (2007). "Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis." Neurology 68(10): 737-42 PMID: 17182976

Cabrera, M. A., S. M. de Andrade, et al. (2012). "Lipids and all-cause mortality among older adults: a 12-year follow-up study." ScientificWorldJournal 2012: 930139 PMID: 22666169

Olsen, T. S., R. H. Christensen, et al. (2007). "Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the Copenhagen Stroke Study." Stroke 38(10): 2646-51 PMID: 17761907

Petursson, H., J. A. Sigurdsson, et al. (2012). "Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study." J Eval Clin Pract 18(1): 159-68 PMID: 21951982